Back to resultsOrange Juice, Hesperidin and Their Role in Vascular Health Benefit (HESPER-HEALTH)
Primary Purpose
Metabolic Syndrome, Vascular Compliance, Predisposition to Cardiovascular Disease
Status
Active
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
Beverage consumption
Sponsored by
About this trial
This is an interventional basic science trial for Metabolic Syndrome focused on measuring Cardiovascular disease prevention, Endothelial dysfunction, Orange juice, Flavanone, Hesperidin, Nutrition Assessment, Nutritional Physiological Phenomena
Eligibility Criteria
Inclusion Criteria:
- Man or post-menopausal woman ;
- 40-65 years old (inclusive) ;
- Body Mass Index (BMI)≤ 30 ;
- Waist circumference ≥80 cm for women, and ≥94 cm for men ;
- Weight > 46 kg
- Normal biological balance sheet or considered normal by the investigator
- No aversion or intolerance to citrus foods ;
- Accept to limit their total intake of flavonoid rich beverages (tea, coffee, cocoa, wine, fruit juice) to 250 mL/day ;
- Ability to give informed consent to participate in research ;
- Willingness to accept randomization and undergo the testing and intervention procedures and deliver stool, blood and urine samples for testing ;
- Affiliation to Social Security.
Exclusion Criteria:
- Treated pre-diabetic or diabetic ;
- Treated for hypertension ;
- Use of statins or other medications for lowering cholesterol ;
- Treated with antibiotics, antifungals, probiotics or prebiotics in the 3 months before the enrolment ;
- Menopausal hormone replacement therapy ;
- Diagnosed gastrointestinal illness in the judgement of the investigator ;
- Any serious medical condition that precludes safe participation in the study, such as coronary artery disease, peripheral vascular disease, stroke, congestive heart failure, chronic obstructive pulmonary disease, insulin-dependent diabetes, psychiatric disease, renal disease, liver disease, active cancer and anemia ;
- History of eating disorders such as bulimia nervosa, anorexia nervosa and severe binge eating disorder in the last 5 years ;
- Digestive disorders with diarrhea during the 3 months preceding the beginning of the study ;
- Self-declared vegetarian, vegetalian, vegan ;
- History of substance abuse or alcohol abuse ;
- Involvement in a weight loss intervention program (including anti-obesity medication) within the past 3 months or who have had bariatric surgery ;
- Current smokers (within the last 30 days) ;
- Use of dietary supplements (vitamins, antioxidants) currently or in the past one month ;
- Strenuous exercise greater than 6 hours per week ;
- Anyone who in the opinion of the investigator is unlikely to be able to comply with the protocol ;
- Subjects involved in another clinical trial or being in the exclusion period of another study or having received a total compensation greater than 4,500 euros over the 12 months preceding the start of the trial ;
- Subject benefiting from a legal protection measure (curatorship, guardianship, safeguard of justice) ;
- Refusal to participate.
Sites / Locations
- University Hospital, Clermont Ferrand
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Placebo Comparator
Experimental
Arm Label
Orange juice (A)
Control beverage (B)
Control beverage supplemented with hesperidin formulation (B+HESP)
Arm Description
42 subjects between 40 and 65 years old with predisposition to cardiovascular disease will consume daily 330 ml of orange juice naturally rich in hesperidin (drink A) during 6 weeks
42 subjects between 40 and 65 years old with predisposition to cardiovascular disease will consume daily 330 ml of control beverage (drink B)- a soft drink with sugar concentration identical to drink A - during 6 weeks
42 subjects between 40 and 65 years old with predisposition to cardiovascular disease will consume daily 330 ml of control beverage (identical to drink B but supplemented with hesperidin to reach level of drink A) during 6 weeks
Outcomes
Primary Outcome Measures
Brachial artery Flow Mediated Dilation (FMD)
The endothelial function will be assessed using the non-invasive ultrasound technique of flow mediated dilatation of the brachial artery. FMD measure is the percentage of dilation of brachial artery in response to a reactive hyperaemia induced by the release of a transient occlusion of the brachial artery in fasted state
Brachial artery Flow Mediated Dilation (FMD)
The endothelial function will be assessed using the non-invasive ultrasound technique of flow mediated dilatation of the brachial artery. FMD measure is the percentage of dilation of brachial artery in response to a reactive hyperaemia induced by the release of a transient occlusion of the brachial artery in fasted state
Brachial artery Flow Mediated Dilation (FMD)
The endothelial function will be assessed using the non-invasive ultrasound technique of flow mediated dilatation of the brachial artery. FMD measure is the percentage of dilation of brachial artery in response to a reactive hyperaemia induced by the release of a transient occlusion of the brachial artery in fasted state
Brachial artery Flow Mediated Dilation (FMD)
The endothelial function will be assessed using the non-invasive ultrasound technique of flow mediated dilatation of the brachial artery. FMD measure is the percentage of dilation of brachial artery in response to a reactive hyperaemia induced by the release of a transient occlusion of the brachial artery in fasted state
Brachial artery Flow Mediated Dilation (FMD)
The endothelial function will be assessed using the non-invasive ultrasound technique of flow mediated dilatation of the brachial artery. FMD measure is the percentage of dilation of brachial artery in response to a reactive hyperaemia induced by the release of a transient occlusion of the brachial artery in fasted state
Brachial artery Flow Mediated Dilation (FMD)
The endothelial function will be assessed using the non-invasive ultrasound technique of flow mediated dilatation of the brachial artery. FMD measure is the percentage of dilation of brachial artery in response to a reactive hyperaemia induced by the release of a transient occlusion of the brachial artery in fasted state
Secondary Outcome Measures
Sex
Participant sex (man/women) will be requested.
Age
Participant age (years) will be requested.
Basal Systolic Blood Pressure
Blood pressure measure (mm Hg) with monitor.
Basal Heart Rate
Heart rate measure (beat/min) with monitor.
D-3 visit systolic Blood Pressure (BP)
Self-monitored blood pressure (mmHg) at home with tensiometer, at home the morning, 3 days before the visit, in fasted state.
D-3 visit diastolic BP
Self-monitored blood pressure (mmHg) at home with tensiometer, at home the morning, 3 days before the visit, in fasted state.
D-3 visit Heart Rate
Self-monitored heart rate (beat/min) at home with tensiometer,at home the morning, 3 days before the visit, in fasted state.
FMD post prandial endothelial response 3h after a challenge meal
Assessment of the postprandial endothelial response to a challenge meal (900kcal, fresh cream, sucrose and milk proteins) by measuring FMD (percent) using ultrasound technique, 3h after intake of the full daily dose of study products concomitantly with challenge meal.
FMD post prandial endothelial response 6h after a challenge meal
Assessment of the postprandial endothelial response to a challenge meal by measuring FMD (percent) using ultrasound technique, 6h after intake of the full daily dose of study products concomitantly with challenge meal.
Arterial compliance assessment
Noninvasive measure with Sphygmocor (AtCor Medical Pty. Ltd) of pulse transit time between carotid artery and femoral artery. The carotid-femoral Pulse Wave Velocity (PWV) (m/sec) is an established index of arterial stiffness,in fasted state.
Rest flow by Flowmetry Laser Doppler (FLD) in fasted state
Vascular endothelial function in the micro-vascular compartment will be assessed using the measurement of the rest flow using laser-Doppler system at the level of the skin of the hand, in fasted state
Occlusion area by FLD in fasted state
Vascular endothelial function in the micro-vascular compartment will be assessed using the measurement of the occlusion area using laser-Doppler system at the level of the skin of the hand by following the response to a reactive hyperaemia induced by the release of a transient occlusion of the brachial artery (same stimulus as for FMD measurement) in fasted state
Hyperaemia area by FLD in fasted state
Vascular endothelial function in the micro-vascular compartment will be assessed using the measurement of the hyperaemia area using laser-Doppler system at the level of the skin of the hand by following the response to a reactive hyperaemia induced by the release of a transient occlusion of the brachial artery (same stimulus as for FMD measurement) in fasted state
Hyperaemia area / occlusion area ratio by FLD in fasted state
Vascular endothelial function in the micro-vascular compartment will be assessed using the ratio hyperaemia area / occlusion area determined by FLD.
Maximal flow by FLD in fasted state
Vascular endothelial function in the micro-vascular compartment will be assessed using the measurement of the maximal flow using laser-Doppler system at the level of the skin of the hand by following the response to a reactive hyperaemia induced by the release of a transient occlusion of the brachial artery (same stimulus as for FMD measurement), in fasted state
Hyperaemia half time by FLD in fasted state
Vascular endothelial function in the micro-vascular compartment will be assessed using the measurement of the hyperaemia half time using laser-Doppler system at the level of the skin of the hand by following the response to a reactive hyperaemia induced by the release of a transient occlusion of the brachial artery (same stimulus as for FMD measurement), in fasted state
Rest flow by FLD 3h after a challenge meal
Vascular endothelial function in the micro-vascular compartment will be assessed using the measurement of the rest flow using laser-Doppler system at the level of the skin of the hand,3h after intake of the full daily dose of study products concomitantly with challenge meal
Occlusion area by FLD 3h after a challenge meal
Vascular endothelial function in the micro-vascular compartment will be assessed using the measurement of the occlusion area using laser-Doppler system at the level of the skin of the hand by following the response to a reactive hyperaemia induced by the release of a transient occlusion of the brachial artery (same stimulus as for FMD measurement), 3h after intake of the full daily dose of study products concomitantly with challenge meal
Hyperaemia area by FLD 3h after a challenge meal
Vascular endothelial function in the micro-vascular compartment will be assessed using the measurement of the hyperaemia area using laser-Doppler system at the level of the skin of the hand by following the response to a reactive hyperaemia induced by the release of a transient occlusion of the brachial artery (same stimulus as for FMD measurement), 3h after intake of the full daily dose of study products concomitantly with challenge meal
Hyperaemia area / occlusion area ratio by FLD 3h after a challenge meal
Vascular endothelial function in the micro-vascular compartment will be assessed using the measurement of the ratio hyperaemia area/ occlusion area determined by FLD, 3h after intake of the full daily dose of study products concomitantly with challenge meal
Maximal flow by FLD 3h after a challenge meal
Vascular endothelial function in the micro-vascular compartment will be assessed using the measurement of the maximal flow using laser-Doppler system at the level of the skin of the hand by following the response to a reactive hyperaemia induced by the release of a transient occlusion of the brachial artery (same stimulus as for FMD measurement), 3h after intake of the full daily dose of study products concomitantly with challenge meal
Hyperaemia half time by FLD 3h after a challenge meal
Vascular endothelial function in the micro-vascular compartment will be assessed using the measurement of the hyperaemia half time using laser-Doppler system at the level of the skin of the hand by following the response to a reactive hyperaemia induced by the release of a transient occlusion of the brachial artery (same stimulus as for FMD measurement), 3h after intake of the full daily dose of study products concomitantly with challenge meal
Rest flow by FLD 6h after a challenge meal
Vascular endothelial function in the micro-vascular compartment will be assessed using the measurement of the rest flow using laser-Doppler system at the level of the skin of the hand, 6h after intake of the full daily dose of study products concomitantly with challenge meal
Occlusion area by FLD 6h after a challenge meal
Vascular endothelial function in the micro-vascular compartment will be assessed using the measurement of the occlusion area using laser-Doppler system at the level of the skin of the hand by following the response to a reactive hyperaemia induced by the release of a transient occlusion of the brachial artery (same stimulus as for FMD measurement), 6h after intake of the full daily dose of study products concomitantly with challenge meal
Hyperaemia area by FLD 6h after a challenge meal
Vascular endothelial function in the micro-vascular compartment will be assessed using the measurement of the hyperaemia area using laser-Doppler system at the level of the skin of the hand by following the response to a reactive hyperaemia induced by the release of a transient occlusion of the brachial artery (same stimulus as for FMD measurement), 6h after intake of the full daily dose of study products concomitantly with challenge meal
Hyperaemia area / occlusion area ratio by FLD 6h after a challenge meal
Vascular endothelial function in the micro-vascular compartment will be assessed using the measurement of the ratio hyperaemia area / occlusion area ratio determined by FLD, 6h after intake of the full daily dose of study products concomitantly with challenge meal
Maximal flow by FLD 6h after a challenge meal
Vascular endothelial function in the micro-vascular compartment will be assessed using the measurement of the maximal flow using laser-Doppler system at the level of the skin of the hand by following the response to a reactive hyperaemia induced by the release of a transient occlusion of the brachial artery (same stimulus as for FMD measurement), 6h after intake of the full daily dose of study products concomitantly with challenge meal
Hyperaemia half time by FLD 6h after a challenge meal
Vascular endothelial function in the micro-vascular compartment will be assessed using the measurement of the hyperaemia half time using laser-Doppler system at the level of the skin of the hand by following the response to a reactive hyperaemia induced by the release of a transient occlusion of the brachial artery (same stimulus as for FMD measurement), 6h after intake of the full daily dose of study products concomitantly with challenge meal
Hesperetin concentration in 24h urine
Concentration of hesperetin in urine (nM) will be measured.
Hesperetin concentration in plasma on fasted state
Concentration of hesperetin in plasma (nM) will be measured.
Hesperetin catabolites concentration in plasma on fasted state
Concentration of hesperetin microbial catabolites in plasma (nM) will be measured, on fasted state
Hesperetin concentration in plasma on 3h post prandial test
Concentration of hesperetin in plasma (mM) will be measured, in post prandial state 3h after the concomitant consumption of the study drink and challenge meal.
Hesperetin catabolites concentration in plasma on 3h post prandial test
Concentration of hesperetin microbial catabolites in plasma (mM) will be measured, in post prandial state 3h after the concomitant consumption of the study drink and challenge meal.
Hesperetin concentration in plasma on 6h post prandial test
Concentration of hesperetin in plasma (mM) will be measured, in post prandial state 6h after the concomitant consumption of the study drink and challenge meal.
Hesperetin catabolites concentration in plasma on 6h post prandial test
Concentration of hesperetin microbial catabolites in plasma (mM) will be measured, in post prandial state 6h after the concomitant consumption of the study drink and challenge meal.
Naringenin concentration in 24h urine
Concentration of naringenin in urine (nM) will be measured.
Naringenin catabolites concentration in 24h urine
Concentration of naringenin microbial catabolites in urine (nM) will be measured.
Naringenin concentration in plasma on fasted state
Concentration of naringenin in plasma (nM) will be measured, on fasted state
Naringenin catabolites concentration in plasma on fasted state
Concentration of naringenin microbial catabolites in plasma (nM) will be measured, on fasted state
Naringenin concentration in plasma on 3h post prandial test
Concentration of naringenin in plasma (mM) will be measured, in post prandial state 3h after the concomitant consumption of the study drink and challenge meal.
Naringenin catabolites concentration in plasma on 3h post prandial test
Concentration of naringenin microbial catabolites in plasma (mM) will be measured, in post prandial state 3h after the concomitant consumption of the study drink and challenge meal.
Naringenin concentration in plasma on 6h post prandial test
Concentration of naringenin in plasma (mM) will be measure, in post prandial state 6h after the concomitant consumption of the study drink and challenge meal.
Naringenin catabolites concentration in plasma on 6h post prandial test
Concentration of naringenin microbial catabolites in plasma (mM) will be measured, in post prandial state 6h after the concomitant consumption of the study drink and challenge meal.
Flavanone concentration in 24h urine
Concentration of flavanone in urine (nM) will be measured.
Flavanone catabolites concentration in 24h urine
Concentration of flavanone microbial catabolites in urine (nM) will be measured.
Flavanone concentration in plasma on fasted state
Concentration of flavanone in plasma (nM) will be measured, on fasted state.
Flavanone catabolites concentration in plasma on fasted state
Concentration of flavanone microbial catabolites in plasma (nM) will be measured, on fasted state
Flavanone concentration in plasma on 3h post prandial test
Concentration of flavanone in plasma (mM) will be measured, in post prandial state 3h after the concomitant consumption of the study drink and challenge meal.
Flavanone catabolites concentration in plasma on 3h post prandial test
Concentration of flavanone microbial catabolites in plasma (mM) will be measured,in post prandial state 3h after the concomitant consumption of the study drink and challenge meal.
Flavanone concentration in plasma on 6h post prandial test
Concentration of flavanone in urine (nM) will be measured, in post prandial state 6h after the concomitant consumption of the study drink and challenge meal.
Flavanone catabolites concentration in plasma on 6h post prandial test
Concentration of flavanone microbial catabolites in plasma (mM) will be measured, in post prandial state 6h after the concomitant consumption of the study drink and challenge meal.
Plasma nitrites dosage
Determination of nitrite plasma concentration (nM) (a biomarker of endothelial activation), on fasted state
Plasma nitroso-thiols dosage
Determination of nitroso-thiols plasma concentration (nM) (a biomarker of endothelial activation), on fasted state
Plasma Inter-Cellular Adhesion Molecules (ICAM) dosage on fasted state
Determination of ICAM plasma concentration (ng/ml) (a biomarker of endothelial activation), on fasted state
Plasma ICAM dosage on 6h post prandial state
Determination of ICAM plasma concentration (ng/ml) (a biomarker of endothelial activation), on 6h post prandial state
Plasma Vascular-CAM (VCAM) dosage on fasted state
Determination of VCAM plasma concentration (ng/ml) (a biomarker of endothelial activation), on fasted state
Plasma VCAM dosage on 6h post prandial state
Determination of VCAM plasma concentration (ng/ml) (a biomarker of endothelial activation), on 6h post prandial state
Plasma e-selectin dosage on fasted state
Determination of e-selectin plasma concentration (ng/ml) (a biomarker of endothelial activation), on fasted state
Plasma e-selectin dosage on 6h post prandial state
Determination of e-selectin plasma concentration (ng/ml) (a biomarker of endothelial activation), on 6h post prandial state
Plasma Extracellular Vesicles analyses (EVs) on fasted state
EVs (a biomarker of endothelial activation) will be isolated from platelet-poor plasma samples and analyzed, on fasted state
EVs analyses on 3h post prandial state
EVs (a biomarker of endothelial activation) will be isolated from platelet-poor plasma samples and analyzed, on post prandial state 3h after the concomitant consumption of the study drink and challenge meal.
Plasma oxylipins identification on fasted state
Determination of oxylipins present in plasma (a biomarker of inflammation and oxidative stress) using a method of profiling, on fasted state
Plasma oxylipin concentration on fasted state
Determination of oxylipin plasma concentration (a biomarker of inflammation and oxidative stress), on fasted state
Plasma oxylipins identification on 6h post prandial state
Determination of oxylipins present in plasma (a biomarker of inflammation and oxidative stress) using a method of profiling, on post-prandial state 6h after the concomitant consumption of the study drink and challenge meal.
Plasma oxylipin concentration on 6h post prandial state
Determination of oxylipin plasma concentration (a biomarker of inflammation and oxidative stress), on post-prandial state 6h after the concomitant consumption of the study drink and challenge meal.
Plasma Interleukin 6 (IL-6) dosage
Determination of IL-6 plasma concentration (pg/ml) (a biomarker of inflammation and oxidative stress), on fasted state
Plasma Tumor Necrosis Factor α (TNFα) dosage
Determination of TNFα plasma concentration (pg/ml) (a biomarker of inflammation and oxidative stress), on fasted state
Plasma high-sensitivity C-reactive protein (hs-CRP) dosage
Determination of hs-CRP plasma concentration (mg/L) (a biomarker of inflammation and oxidative stress), on fasted state
Plasma glucose dosage on fasted state
Determination of glucose plasma concentration (mM) (a metabolic parameter), on fasted state
Plasma glucose dosage on 3h post prandial state
Determination of glucose plasma concentration (mM) (a metabolic parameter), on post-prandial state 3h after the concomitant consumption of the study drink and challenge meal.
Plasma glucose dosage on 6h post prandial state
Determination of glucose plasma concentration (mM) (a metabolic parameter), on post-prandial state 6h after the concomitant consumption of the study drink and challenge meal.
-Plasma Triacylglycerol (TAG) dosage on fasted state
Determination of TAG plasma concentration (g/L) (a metabolic parameter), on fasted state
Plasma TAG dosage on 3h post prandial state
Determination of TAG plasma concentration (g/L) (a metabolic parameter), on post-prandial state 3h after the concomitant consumption of the study drink and challenge meal, on post-prandial state 3h after the concomitant consumption of the study drink and challenge meal.
Plasma TAG dosage on 6h post prandial state
Determination of TAG plasma concentration (g/L) (a metabolic parameter), on post-prandial state 6h after the concomitant consumption of the study drink and challenge meal.
Plasma uric acid dosage on fasted state
Determination of uric acid plasma concentration (mM) (a metabolic parameter) method, on fasted state
Plasma uric acid on 3h post prandial state
Determination of uric acid plasma concentration (mM) (metabolic parameter), on post-prandial state 3h after the concomitant consumption of the study drink and challenge meal.
Plasma uric acid on 6h post prandial state
Determination of uric acid plasma concentration (mM) (metabolic parameter) will be determined, on post-prandial state 6h after the concomitant consumption of the study drink and challenge meal.
Plasma total cholesterol dosage
Determination of total cholesterol plasma concentration (mM) (a metabolic parameter), on fasted state
Plasma High Density Lipoprotein cholesterol (HDL-chol) dosage
Determination of HDL-chol plasma concentration (mM) (a metabolic parameter), on fasted state
Plasma High Density Lipoprotein cholesterol (LDL-chol) calculation
Determination of LDL-chol plasma concentration (mM) (metabolic parameter), on fasted state
Plasma Total Fatty Acids (FA) dosage
Determination of total FA plasma concentration (mM) (a metabolic parameter), on fasted state
Serum Insulin dosage
Determination of insulin serum concentration (mU/L or pM) (a metabolic parameter), on fasted state
Weight measure
the body weight (kg) will be recorded with a bathroom scale, on fasted state
Height measure
the body height (cm) will be measured with a stadiometer.
Body Mass Index (BMI) calculation
the BMI (kg/m²) will be calculated, on fasted state
Waist circumference measure
the waist circumference (cm) will be recorded with a measuring tape, on fasted state
Fat mass ratio determination
The percentage of fat mass (percent) (body composition) will be determined on each participant using a multi-frequency bioelectrical Impedance Analyzer, on fasted state
Lean mass ratio determination
The percentage of lean mass (percent) (body composition) will be determined on each participant using a multi-frequency bioelectrical Impedance Analyzer, on fasted state
Water mass ratio determination
The percentage of water (percent) (body composition) will be determined using a multi-frequency bioelectrical Impedance Analyzer, on fasted state
RNA profiling on fasted state
Nutrigenomic analysis will be performed from total Ribo Nucleic Acid (RNA) isolated blood collected in PAXgene Blood RNA Tube. The isolated RNA will be used to perform microarray analyses that allow identification of expression of all genes of the genome, on fasted state
RNA profiling on 6h post prandial state
Analysis will be performed from total RNA isolated blood collected in PAXgene Blood RNA Tube. The isolated RNA will be used to perform microarray analyses that allow identification of expression of all genes of the genome, on post-prandial state 6h after the concomitant consumption of the study drink and challenge meal.
Gut microbiota profiling
Identification of the microbiota composition of feces samples (collected by subjects) by performing a genetic sequencing analysis of bacterial DNA.
Plasma carotenoids dosage
Carotenoids will be quantitated from plasma (nM), on fasted state
Plasma vitamine C dosage
Vitamin C status will be quantified in deproteinized plasma (mg/L), on fasted state
Treatment compliance
Treatment compliance (percent) will be determined using counting of empty orange drinks brought back by volunteers after the consumption periods
Polyphenol intake
Polyphenol intake (ml/day) in basal and during treatment consumption periods will be determined by a dietician using food report completed by volunteers.
Low-polyphenol diet compliance
Respect (y/n) of a low-polyphenol diet in basal (between Visit 1 - Visit 2) and during treatment consumption periods (between Visit 2 - Visit 3, Visit 4 - Visit 5, Visit 6 - Visit 7) will be determined by a dietician using 3 days food reports completed by volunteers.
Calorie intake
Calorie (kcal/day) intake in basal and during treatment consumption periods will be determined by a dietician using food report completed by volunteers.
Protein intake
Protein (g/day) intake in basal and during treatment consumption periods will be determined by a dietician using food report completed by volunteers.
Lipid intake
Lipid intake (g/day) in basal and during treatment consumption periods will be determined by a dietician using food report completed by volunteers.
Carbohydrate intake
Carbohydrate intake (g/day) in basal and during treatment consumption periods will be determined by a dietician using food report completed by volunteers.
Diet division of protein/lipid/carbohydrate intakes
The overall distribution of the protein/lipid/carbohydrate food intakes (%) will be determined by a dietician using food report completed by volunteers.
Diet stability
Diet stability (y/n) in terms of polyphenols, calories, proteins, carbohydrates and lipids intakes during the whole study will be determined by a dietician using the 4 food reports completed by volunteers.
Biobank for food metabolome
Urine samples will be stored for further assessment of food metabolome to potentially identify new bioactive compounds present in the juice that could contribute to the biological response after orange juice/HESP intake.
Full Information
NCT ID
NCT04731987
First Posted
January 22, 2021
Last Updated
February 21, 2023
Sponsor
University Hospital, Clermont-Ferrand
Collaborators
UMR 1019, Unité de Nutrition Humaine, INRAE, Auvergne-Rhône Alpes Center, Department of Beverage Research, Chair of analysis and technology of plant-based foods, Geisenheim University, European Fruit Juice Association (AIJN)
1. Study Identification
Unique Protocol Identification Number
NCT04731987
Brief Title
Orange Juice, Hesperidin and Their Role in Vascular Health Benefit
Acronym
HESPER-HEALTH
Official Title
Orange Juice, Hesperidin and Their Role in Vascular Health Benefit: a Human Double Blind, Randomized, Controlled, Cross Over Study
Study Type
Interventional
2. Study Status
Record Verification Date
June 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
February 24, 2021 (Actual)
Primary Completion Date
June 30, 2023 (Anticipated)
Study Completion Date
June 30, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Clermont-Ferrand
Collaborators
UMR 1019, Unité de Nutrition Humaine, INRAE, Auvergne-Rhône Alpes Center, Department of Beverage Research, Chair of analysis and technology of plant-based foods, Geisenheim University, European Fruit Juice Association (AIJN)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
Although epidemiological studies have associated the consumption of sugary beverages with adverse health effects, experimental studies have demonstrated that the metabolic response of the human body to fruit juice as compared to artificial beverages is substantially different. Fruit juices do not just provide sugars and related calories, but they are rich sources of bioactive compounds especially of flavonoids. Flavanones constitute a class of flavonoids that are specifically and abundantly found in citrus fruits, with hesperidin being the major compound in orange. From prospective cohort studies, higher intakes of flavanones are associated with a lower incidence of mortality by cardiovascular disease (CVD). This relation is supported by results from a number of animal studies demonstrating a slowdown in atherosclerosis development and vascular protective effects in dietary interventions with flavanones. Randomized, controlled clinical trials to corroborate the suggested vasculo-protective effects of orange juice presumably mediated by the flavanones are scarce and available data do not allow to draw firm conclusions about their efficacy. To fill this gap, the "HESPER-HEALTH study" conducted in humans will assess the vascular protective effects of 100% orange juice consumption and evaluate the contribution of hesperidin in these effects.
Detailed Description
This human dietary intervention study is a double blind, randomized, placebo controlled, cross over trial with 3 arms, carried out on subjects with predisposition to cardiovascular diseases (CVD) based on age and overweight. This study aims to demonstrate the vascular protective effects (with Flow Mediated Dilatation (FMD) as main criteria) of the consumption of a flavanone rich orange juice or of orange flavanones by comparison with a control sugary drink alone.
The 42 recruited participants will receive the 3 drinks in a random order. For each subject, the study is divided into 3 identical experimental periods of 45 days (period 1,2,3): including 3 days prior to the beginning of the product intake, during which specific dietary guidelines, samplings and measures will be asked to be performed at home followed by a 6 weeks period of consumption of each of the 3 beverages). A period of 4 to 6 weeks of wash-out is planned between each experimental period.
To summarize: Visit 1 (D-14) = inclusion, Visit 2 (D1: baseline) to 3 (D42) = period 1, Visit 3 (D42) to 4 (D70) = wash out 1, Visit 4 (D70) to 5 (D111) = period 2, Visit 5 (D111) to 6 (D139) = wash out 2, Visit 6 (D139) to 7 (D180) = period 3. The wash-out periods (minimum duration: 4 weeks) may be extended until 6 weeks for the convenience of participants.
The protocol includes a total of 7 visits to PIC/CIC Inserm 1405 of the Clermont-Fd University Hospital.
The total duration of the study will be between 28 and 34 weeks
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metabolic Syndrome, Vascular Compliance, Predisposition to Cardiovascular Disease
Keywords
Cardiovascular disease prevention, Endothelial dysfunction, Orange juice, Flavanone, Hesperidin, Nutrition Assessment, Nutritional Physiological Phenomena
7. Study Design
Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
drinks kits will be labelled and packaged according to the pre-established randomization plane by the pharmacy department of University Hospital of Clermont-Ferrand, France. Kits will be distributed in a blind fashion for each cross over period on the basis of the randomization schedule.
Allocation
Randomized
Enrollment
42 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Orange juice (A)
Arm Type
Experimental
Arm Description
42 subjects between 40 and 65 years old with predisposition to cardiovascular disease will consume daily 330 ml of orange juice naturally rich in hesperidin (drink A) during 6 weeks
Arm Title
Control beverage (B)
Arm Type
Placebo Comparator
Arm Description
42 subjects between 40 and 65 years old with predisposition to cardiovascular disease will consume daily 330 ml of control beverage (drink B)- a soft drink with sugar concentration identical to drink A - during 6 weeks
Arm Title
Control beverage supplemented with hesperidin formulation (B+HESP)
Arm Type
Experimental
Arm Description
42 subjects between 40 and 65 years old with predisposition to cardiovascular disease will consume daily 330 ml of control beverage (identical to drink B but supplemented with hesperidin to reach level of drink A) during 6 weeks
Intervention Type
Behavioral
Intervention Name(s)
Beverage consumption
Intervention Description
Volunteers will consume, in random order, daily 330 ml of 1 experimental beverage per period (Orange Juice, Control Beverage, Control Beverage supplemented with hesperidin) for 6 weeks in each period.
At the beginning and the end of each period, exploration will be conducted at fasted state and at post-prandial state after the administration of a high-fat high-sugar meal.
Primary Outcome Measure Information:
Title
Brachial artery Flow Mediated Dilation (FMD)
Description
The endothelial function will be assessed using the non-invasive ultrasound technique of flow mediated dilatation of the brachial artery. FMD measure is the percentage of dilation of brachial artery in response to a reactive hyperaemia induced by the release of a transient occlusion of the brachial artery in fasted state
Time Frame
Day 1
Title
Brachial artery Flow Mediated Dilation (FMD)
Description
The endothelial function will be assessed using the non-invasive ultrasound technique of flow mediated dilatation of the brachial artery. FMD measure is the percentage of dilation of brachial artery in response to a reactive hyperaemia induced by the release of a transient occlusion of the brachial artery in fasted state
Time Frame
Day 42
Title
Brachial artery Flow Mediated Dilation (FMD)
Description
The endothelial function will be assessed using the non-invasive ultrasound technique of flow mediated dilatation of the brachial artery. FMD measure is the percentage of dilation of brachial artery in response to a reactive hyperaemia induced by the release of a transient occlusion of the brachial artery in fasted state
Time Frame
Day 70
Title
Brachial artery Flow Mediated Dilation (FMD)
Description
The endothelial function will be assessed using the non-invasive ultrasound technique of flow mediated dilatation of the brachial artery. FMD measure is the percentage of dilation of brachial artery in response to a reactive hyperaemia induced by the release of a transient occlusion of the brachial artery in fasted state
Time Frame
Day 111
Title
Brachial artery Flow Mediated Dilation (FMD)
Description
The endothelial function will be assessed using the non-invasive ultrasound technique of flow mediated dilatation of the brachial artery. FMD measure is the percentage of dilation of brachial artery in response to a reactive hyperaemia induced by the release of a transient occlusion of the brachial artery in fasted state
Time Frame
Day 139
Title
Brachial artery Flow Mediated Dilation (FMD)
Description
The endothelial function will be assessed using the non-invasive ultrasound technique of flow mediated dilatation of the brachial artery. FMD measure is the percentage of dilation of brachial artery in response to a reactive hyperaemia induced by the release of a transient occlusion of the brachial artery in fasted state
Time Frame
Day 180
Secondary Outcome Measure Information:
Title
Sex
Description
Participant sex (man/women) will be requested.
Time Frame
Day -14
Title
Age
Description
Participant age (years) will be requested.
Time Frame
Day 34
Title
Basal Systolic Blood Pressure
Description
Blood pressure measure (mm Hg) with monitor.
Time Frame
Day -14
Title
Basal Heart Rate
Description
Heart rate measure (beat/min) with monitor.
Time Frame
Day -14
Title
D-3 visit systolic Blood Pressure (BP)
Description
Self-monitored blood pressure (mmHg) at home with tensiometer, at home the morning, 3 days before the visit, in fasted state.
Time Frame
Day 1, Day 42, Day 70, Day 111, Day 139, Day 180
Title
D-3 visit diastolic BP
Description
Self-monitored blood pressure (mmHg) at home with tensiometer, at home the morning, 3 days before the visit, in fasted state.
Time Frame
Day 1, Day 42, Day 70, Day 111, Day 139, Day 180
Title
D-3 visit Heart Rate
Description
Self-monitored heart rate (beat/min) at home with tensiometer,at home the morning, 3 days before the visit, in fasted state.
Time Frame
Day 1, Day 42, Day 70, Day 111, Day 139, Day 180
Title
FMD post prandial endothelial response 3h after a challenge meal
Description
Assessment of the postprandial endothelial response to a challenge meal (900kcal, fresh cream, sucrose and milk proteins) by measuring FMD (percent) using ultrasound technique, 3h after intake of the full daily dose of study products concomitantly with challenge meal.
Time Frame
Day 1, Day 42, Day 70, Day 111, Day 139, Day 180
Title
FMD post prandial endothelial response 6h after a challenge meal
Description
Assessment of the postprandial endothelial response to a challenge meal by measuring FMD (percent) using ultrasound technique, 6h after intake of the full daily dose of study products concomitantly with challenge meal.
Time Frame
Day 1, Day 42, Day 70, Day 111, Day 139, Day 180
Title
Arterial compliance assessment
Description
Noninvasive measure with Sphygmocor (AtCor Medical Pty. Ltd) of pulse transit time between carotid artery and femoral artery. The carotid-femoral Pulse Wave Velocity (PWV) (m/sec) is an established index of arterial stiffness,in fasted state.
Time Frame
Day 1, Day 42, Day 70, Day 111, Day 139, Day 180
Title
Rest flow by Flowmetry Laser Doppler (FLD) in fasted state
Description
Vascular endothelial function in the micro-vascular compartment will be assessed using the measurement of the rest flow using laser-Doppler system at the level of the skin of the hand, in fasted state
Time Frame
Day 1, Day 42, Day 70, Day 111, Day 139, Day 180
Title
Occlusion area by FLD in fasted state
Description
Vascular endothelial function in the micro-vascular compartment will be assessed using the measurement of the occlusion area using laser-Doppler system at the level of the skin of the hand by following the response to a reactive hyperaemia induced by the release of a transient occlusion of the brachial artery (same stimulus as for FMD measurement) in fasted state
Time Frame
Day 1, Day 42, Day 70, Day 111, Day 139, Day 180
Title
Hyperaemia area by FLD in fasted state
Description
Vascular endothelial function in the micro-vascular compartment will be assessed using the measurement of the hyperaemia area using laser-Doppler system at the level of the skin of the hand by following the response to a reactive hyperaemia induced by the release of a transient occlusion of the brachial artery (same stimulus as for FMD measurement) in fasted state
Time Frame
Day 1, Day 42, Day 70, Day 111, Day 139, Day 180
Title
Hyperaemia area / occlusion area ratio by FLD in fasted state
Description
Vascular endothelial function in the micro-vascular compartment will be assessed using the ratio hyperaemia area / occlusion area determined by FLD.
Time Frame
Day 1, Day 42, Day 70, Day 111, Day 139, Day 180
Title
Maximal flow by FLD in fasted state
Description
Vascular endothelial function in the micro-vascular compartment will be assessed using the measurement of the maximal flow using laser-Doppler system at the level of the skin of the hand by following the response to a reactive hyperaemia induced by the release of a transient occlusion of the brachial artery (same stimulus as for FMD measurement), in fasted state
Time Frame
Day 1, Day 42, Day 70, Day 111, Day 139, Day 180
Title
Hyperaemia half time by FLD in fasted state
Description
Vascular endothelial function in the micro-vascular compartment will be assessed using the measurement of the hyperaemia half time using laser-Doppler system at the level of the skin of the hand by following the response to a reactive hyperaemia induced by the release of a transient occlusion of the brachial artery (same stimulus as for FMD measurement), in fasted state
Time Frame
Day 1, Day 42, Day 70, Day 111, Day 139, Day 180
Title
Rest flow by FLD 3h after a challenge meal
Description
Vascular endothelial function in the micro-vascular compartment will be assessed using the measurement of the rest flow using laser-Doppler system at the level of the skin of the hand,3h after intake of the full daily dose of study products concomitantly with challenge meal
Time Frame
Day 1, Day 42, Day 70, Day 111, Day 139, Day 180
Title
Occlusion area by FLD 3h after a challenge meal
Description
Vascular endothelial function in the micro-vascular compartment will be assessed using the measurement of the occlusion area using laser-Doppler system at the level of the skin of the hand by following the response to a reactive hyperaemia induced by the release of a transient occlusion of the brachial artery (same stimulus as for FMD measurement), 3h after intake of the full daily dose of study products concomitantly with challenge meal
Time Frame
Day 1, Day 42, Day 70, Day 111, Day 139, Day 180
Title
Hyperaemia area by FLD 3h after a challenge meal
Description
Vascular endothelial function in the micro-vascular compartment will be assessed using the measurement of the hyperaemia area using laser-Doppler system at the level of the skin of the hand by following the response to a reactive hyperaemia induced by the release of a transient occlusion of the brachial artery (same stimulus as for FMD measurement), 3h after intake of the full daily dose of study products concomitantly with challenge meal
Time Frame
Day 1, Day 42, Day 70, Day 111, Day 139, Day 180
Title
Hyperaemia area / occlusion area ratio by FLD 3h after a challenge meal
Description
Vascular endothelial function in the micro-vascular compartment will be assessed using the measurement of the ratio hyperaemia area/ occlusion area determined by FLD, 3h after intake of the full daily dose of study products concomitantly with challenge meal
Time Frame
Day 1, Day 42, Day 70, Day 111, Day 139, Day 180
Title
Maximal flow by FLD 3h after a challenge meal
Description
Vascular endothelial function in the micro-vascular compartment will be assessed using the measurement of the maximal flow using laser-Doppler system at the level of the skin of the hand by following the response to a reactive hyperaemia induced by the release of a transient occlusion of the brachial artery (same stimulus as for FMD measurement), 3h after intake of the full daily dose of study products concomitantly with challenge meal
Time Frame
Day 1, Day 42, Day 70, Day 111, Day 139, Day 180
Title
Hyperaemia half time by FLD 3h after a challenge meal
Description
Vascular endothelial function in the micro-vascular compartment will be assessed using the measurement of the hyperaemia half time using laser-Doppler system at the level of the skin of the hand by following the response to a reactive hyperaemia induced by the release of a transient occlusion of the brachial artery (same stimulus as for FMD measurement), 3h after intake of the full daily dose of study products concomitantly with challenge meal
Time Frame
Day 1, Day 42, Day 70, Day 111, Day 139, Day 180
Title
Rest flow by FLD 6h after a challenge meal
Description
Vascular endothelial function in the micro-vascular compartment will be assessed using the measurement of the rest flow using laser-Doppler system at the level of the skin of the hand, 6h after intake of the full daily dose of study products concomitantly with challenge meal
Time Frame
Day 1, Day 42, Day 70, Day 111, Day 139, Day 180
Title
Occlusion area by FLD 6h after a challenge meal
Description
Vascular endothelial function in the micro-vascular compartment will be assessed using the measurement of the occlusion area using laser-Doppler system at the level of the skin of the hand by following the response to a reactive hyperaemia induced by the release of a transient occlusion of the brachial artery (same stimulus as for FMD measurement), 6h after intake of the full daily dose of study products concomitantly with challenge meal
Time Frame
Day 1, Day 42, Day 70, Day 111, Day 139, Day 180
Title
Hyperaemia area by FLD 6h after a challenge meal
Description
Vascular endothelial function in the micro-vascular compartment will be assessed using the measurement of the hyperaemia area using laser-Doppler system at the level of the skin of the hand by following the response to a reactive hyperaemia induced by the release of a transient occlusion of the brachial artery (same stimulus as for FMD measurement), 6h after intake of the full daily dose of study products concomitantly with challenge meal
Time Frame
Day 1, Day 42, Day 70, Day 111, Day 139, Day 180
Title
Hyperaemia area / occlusion area ratio by FLD 6h after a challenge meal
Description
Vascular endothelial function in the micro-vascular compartment will be assessed using the measurement of the ratio hyperaemia area / occlusion area ratio determined by FLD, 6h after intake of the full daily dose of study products concomitantly with challenge meal
Time Frame
Day 1, Day 42, Day 70, Day 111, Day 139, Day 180
Title
Maximal flow by FLD 6h after a challenge meal
Description
Vascular endothelial function in the micro-vascular compartment will be assessed using the measurement of the maximal flow using laser-Doppler system at the level of the skin of the hand by following the response to a reactive hyperaemia induced by the release of a transient occlusion of the brachial artery (same stimulus as for FMD measurement), 6h after intake of the full daily dose of study products concomitantly with challenge meal
Time Frame
Day 1, Day 42, Day 70, Day 111, Day 139, Day 180
Title
Hyperaemia half time by FLD 6h after a challenge meal
Description
Vascular endothelial function in the micro-vascular compartment will be assessed using the measurement of the hyperaemia half time using laser-Doppler system at the level of the skin of the hand by following the response to a reactive hyperaemia induced by the release of a transient occlusion of the brachial artery (same stimulus as for FMD measurement), 6h after intake of the full daily dose of study products concomitantly with challenge meal
Time Frame
Day 1, Day 42, Day 70, Day 111, Day 139, Day 180
Title
Hesperetin concentration in 24h urine
Description
Concentration of hesperetin in urine (nM) will be measured.
Time Frame
Day 1, Day 42, Day 70, Day 111, Day 139, Day 180
Title
Hesperetin concentration in plasma on fasted state
Description
Concentration of hesperetin in plasma (nM) will be measured.
Time Frame
Day 1, Day 42, Day 70, Day 111, Day 139, Day 180
Title
Hesperetin catabolites concentration in plasma on fasted state
Description
Concentration of hesperetin microbial catabolites in plasma (nM) will be measured, on fasted state
Time Frame
Day 1, Day 42, Day 70, Day 111, Day 139, Day 180
Title
Hesperetin concentration in plasma on 3h post prandial test
Description
Concentration of hesperetin in plasma (mM) will be measured, in post prandial state 3h after the concomitant consumption of the study drink and challenge meal.
Time Frame
Day 1, Day 42, Day 70, Day 111, Day 139, Day 180
Title
Hesperetin catabolites concentration in plasma on 3h post prandial test
Description
Concentration of hesperetin microbial catabolites in plasma (mM) will be measured, in post prandial state 3h after the concomitant consumption of the study drink and challenge meal.
Time Frame
Day 1, Day 42, Day 70, Day 111, Day 139, Day 180
Title
Hesperetin concentration in plasma on 6h post prandial test
Description
Concentration of hesperetin in plasma (mM) will be measured, in post prandial state 6h after the concomitant consumption of the study drink and challenge meal.
Time Frame
Day 1, Day 42, Day 70, Day 111, Day 139, Day 180
Title
Hesperetin catabolites concentration in plasma on 6h post prandial test
Description
Concentration of hesperetin microbial catabolites in plasma (mM) will be measured, in post prandial state 6h after the concomitant consumption of the study drink and challenge meal.
Time Frame
Day 1, Day 42, Day 70, Day 111, Day 139, Day 180
Title
Naringenin concentration in 24h urine
Description
Concentration of naringenin in urine (nM) will be measured.
Time Frame
Day 1, Day 42, Day 70, Day 111, Day 139, Day 180
Title
Naringenin catabolites concentration in 24h urine
Description
Concentration of naringenin microbial catabolites in urine (nM) will be measured.
Time Frame
Day 1, Day 42, Day 70, Day 111, Day 139, Day 180
Title
Naringenin concentration in plasma on fasted state
Description
Concentration of naringenin in plasma (nM) will be measured, on fasted state
Time Frame
Day 1, Day 42, Day 70, Day 111, Day 139, Day 180
Title
Naringenin catabolites concentration in plasma on fasted state
Description
Concentration of naringenin microbial catabolites in plasma (nM) will be measured, on fasted state
Time Frame
Day 1, Day 42, Day 70, Day 111, Day 139, Day 180
Title
Naringenin concentration in plasma on 3h post prandial test
Description
Concentration of naringenin in plasma (mM) will be measured, in post prandial state 3h after the concomitant consumption of the study drink and challenge meal.
Time Frame
Day 1, Day 42, Day 70, Day 111, Day 139, Day 180
Title
Naringenin catabolites concentration in plasma on 3h post prandial test
Description
Concentration of naringenin microbial catabolites in plasma (mM) will be measured, in post prandial state 3h after the concomitant consumption of the study drink and challenge meal.
Time Frame
Day 1, Day 42, Day 70, Day 111, Day 139, Day 180
Title
Naringenin concentration in plasma on 6h post prandial test
Description
Concentration of naringenin in plasma (mM) will be measure, in post prandial state 6h after the concomitant consumption of the study drink and challenge meal.
Time Frame
Day 1, Day 42, Day 70, Day 111, Day 139, Day 180
Title
Naringenin catabolites concentration in plasma on 6h post prandial test
Description
Concentration of naringenin microbial catabolites in plasma (mM) will be measured, in post prandial state 6h after the concomitant consumption of the study drink and challenge meal.
Time Frame
Day 1, Day 42, Day 70, Day 111, Day 139, Day 180
Title
Flavanone concentration in 24h urine
Description
Concentration of flavanone in urine (nM) will be measured.
Time Frame
Day 1, Day 42, Day 70, Day 111, Day 139, Day 180
Title
Flavanone catabolites concentration in 24h urine
Description
Concentration of flavanone microbial catabolites in urine (nM) will be measured.
Time Frame
Day 1, Day 42, Day 70, Day 111, Day 139, Day 180
Title
Flavanone concentration in plasma on fasted state
Description
Concentration of flavanone in plasma (nM) will be measured, on fasted state.
Time Frame
Day 1, Day 42, Day 70, Day 111, Day 139, Day 180
Title
Flavanone catabolites concentration in plasma on fasted state
Description
Concentration of flavanone microbial catabolites in plasma (nM) will be measured, on fasted state
Time Frame
Day 1, Day 42, Day 70, Day 111, Day 139, Day 180
Title
Flavanone concentration in plasma on 3h post prandial test
Description
Concentration of flavanone in plasma (mM) will be measured, in post prandial state 3h after the concomitant consumption of the study drink and challenge meal.
Time Frame
Day 1, Day 42, Day 70, Day 111, Day 139, Day 180
Title
Flavanone catabolites concentration in plasma on 3h post prandial test
Description
Concentration of flavanone microbial catabolites in plasma (mM) will be measured,in post prandial state 3h after the concomitant consumption of the study drink and challenge meal.
Time Frame
Day 1, Day 42, Day 70, Day 111, Day 139, Day 180
Title
Flavanone concentration in plasma on 6h post prandial test
Description
Concentration of flavanone in urine (nM) will be measured, in post prandial state 6h after the concomitant consumption of the study drink and challenge meal.
Time Frame
Day 1, Day 42, Day 70, Day 111, Day 139, Day 180
Title
Flavanone catabolites concentration in plasma on 6h post prandial test
Description
Concentration of flavanone microbial catabolites in plasma (mM) will be measured, in post prandial state 6h after the concomitant consumption of the study drink and challenge meal.
Time Frame
Day 1, Day 42, Day 70, Day 111, Day 139, Day 180
Title
Plasma nitrites dosage
Description
Determination of nitrite plasma concentration (nM) (a biomarker of endothelial activation), on fasted state
Time Frame
Day 1, Day 42, Day 70, Day 111, Day 139, Day 180
Title
Plasma nitroso-thiols dosage
Description
Determination of nitroso-thiols plasma concentration (nM) (a biomarker of endothelial activation), on fasted state
Time Frame
Day 1, Day 42, Day 70, Day 111, Day 139, Day 180
Title
Plasma Inter-Cellular Adhesion Molecules (ICAM) dosage on fasted state
Description
Determination of ICAM plasma concentration (ng/ml) (a biomarker of endothelial activation), on fasted state
Time Frame
Day 1, Day 42, Day 70, Day 111, Day 139, Day 180
Title
Plasma ICAM dosage on 6h post prandial state
Description
Determination of ICAM plasma concentration (ng/ml) (a biomarker of endothelial activation), on 6h post prandial state
Time Frame
Day 1, Day 42, Day 70, Day 111, Day 139, Day 180
Title
Plasma Vascular-CAM (VCAM) dosage on fasted state
Description
Determination of VCAM plasma concentration (ng/ml) (a biomarker of endothelial activation), on fasted state
Time Frame
Day 1, Day 42, Day 70, Day 111, Day 139, Day 180
Title
Plasma VCAM dosage on 6h post prandial state
Description
Determination of VCAM plasma concentration (ng/ml) (a biomarker of endothelial activation), on 6h post prandial state
Time Frame
Day 1, Day 42, Day 70, Day 111, Day 139, Day 180
Title
Plasma e-selectin dosage on fasted state
Description
Determination of e-selectin plasma concentration (ng/ml) (a biomarker of endothelial activation), on fasted state
Time Frame
Day 1, Day 42, Day 70, Day 111, Day 139, Day 180
Title
Plasma e-selectin dosage on 6h post prandial state
Description
Determination of e-selectin plasma concentration (ng/ml) (a biomarker of endothelial activation), on 6h post prandial state
Time Frame
Day 1, Day 42, Day 70, Day 111, Day 139, Day 180
Title
Plasma Extracellular Vesicles analyses (EVs) on fasted state
Description
EVs (a biomarker of endothelial activation) will be isolated from platelet-poor plasma samples and analyzed, on fasted state
Time Frame
Day 42, Day 111, Day 180
Title
EVs analyses on 3h post prandial state
Description
EVs (a biomarker of endothelial activation) will be isolated from platelet-poor plasma samples and analyzed, on post prandial state 3h after the concomitant consumption of the study drink and challenge meal.
Time Frame
Day 42, Day 111, Day 180
Title
Plasma oxylipins identification on fasted state
Description
Determination of oxylipins present in plasma (a biomarker of inflammation and oxidative stress) using a method of profiling, on fasted state
Time Frame
Day 1, Day 42, Day 70, Day 111, Day 139, Day 180
Title
Plasma oxylipin concentration on fasted state
Description
Determination of oxylipin plasma concentration (a biomarker of inflammation and oxidative stress), on fasted state
Time Frame
Day 1, Day 42, Day 70, Day 111, Day 139, Day 180
Title
Plasma oxylipins identification on 6h post prandial state
Description
Determination of oxylipins present in plasma (a biomarker of inflammation and oxidative stress) using a method of profiling, on post-prandial state 6h after the concomitant consumption of the study drink and challenge meal.
Time Frame
Day 42, Day 111, Day 180
Title
Plasma oxylipin concentration on 6h post prandial state
Description
Determination of oxylipin plasma concentration (a biomarker of inflammation and oxidative stress), on post-prandial state 6h after the concomitant consumption of the study drink and challenge meal.
Time Frame
Day 42, Day 111, Day 180
Title
Plasma Interleukin 6 (IL-6) dosage
Description
Determination of IL-6 plasma concentration (pg/ml) (a biomarker of inflammation and oxidative stress), on fasted state
Time Frame
Day 1, Day 42, Day 70, Day 111, Day 139, Day 180
Title
Plasma Tumor Necrosis Factor α (TNFα) dosage
Description
Determination of TNFα plasma concentration (pg/ml) (a biomarker of inflammation and oxidative stress), on fasted state
Time Frame
Day 1, Day 42, Day 70, Day 111, Day 139, Day 180
Title
Plasma high-sensitivity C-reactive protein (hs-CRP) dosage
Description
Determination of hs-CRP plasma concentration (mg/L) (a biomarker of inflammation and oxidative stress), on fasted state
Time Frame
Day -14, Day 1, Day 42, Day 70, Day 111, Day 139, Day 180
Title
Plasma glucose dosage on fasted state
Description
Determination of glucose plasma concentration (mM) (a metabolic parameter), on fasted state
Time Frame
Day -14, Day 1, Day 42, Day 70, Day 111, Day 139, Day 180
Title
Plasma glucose dosage on 3h post prandial state
Description
Determination of glucose plasma concentration (mM) (a metabolic parameter), on post-prandial state 3h after the concomitant consumption of the study drink and challenge meal.
Time Frame
Day 1, Day 42, Day 70, Day 111, Day 139, Day 180
Title
Plasma glucose dosage on 6h post prandial state
Description
Determination of glucose plasma concentration (mM) (a metabolic parameter), on post-prandial state 6h after the concomitant consumption of the study drink and challenge meal.
Time Frame
Day 1, Day 42, Day 70, Day 111, Day 139, Day 180
Title
-Plasma Triacylglycerol (TAG) dosage on fasted state
Description
Determination of TAG plasma concentration (g/L) (a metabolic parameter), on fasted state
Time Frame
Day -14, Day 1, Day 42, Day 70, Day 111, Day 139, Day 180
Title
Plasma TAG dosage on 3h post prandial state
Description
Determination of TAG plasma concentration (g/L) (a metabolic parameter), on post-prandial state 3h after the concomitant consumption of the study drink and challenge meal, on post-prandial state 3h after the concomitant consumption of the study drink and challenge meal.
Time Frame
Day 1, Day 42, Day 70, Day 111, Day 139, Day 180
Title
Plasma TAG dosage on 6h post prandial state
Description
Determination of TAG plasma concentration (g/L) (a metabolic parameter), on post-prandial state 6h after the concomitant consumption of the study drink and challenge meal.
Time Frame
Day 1, Day 42, Day 70, Day 111, Day 139, Day 180
Title
Plasma uric acid dosage on fasted state
Description
Determination of uric acid plasma concentration (mM) (a metabolic parameter) method, on fasted state
Time Frame
Day 1, Day 42, Day 70, Day 111, Day 139, Day 180
Title
Plasma uric acid on 3h post prandial state
Description
Determination of uric acid plasma concentration (mM) (metabolic parameter), on post-prandial state 3h after the concomitant consumption of the study drink and challenge meal.
Time Frame
Day 1, Day 42, Day 70, Day 111, Day 139, Day 180
Title
Plasma uric acid on 6h post prandial state
Description
Determination of uric acid plasma concentration (mM) (metabolic parameter) will be determined, on post-prandial state 6h after the concomitant consumption of the study drink and challenge meal.
Time Frame
Day 1, Day 42, Day 70, Day 111, Day 139, Day 180
Title
Plasma total cholesterol dosage
Description
Determination of total cholesterol plasma concentration (mM) (a metabolic parameter), on fasted state
Time Frame
Day -14, Day 1, Day 42, Day 70, Day 111, Day 139, Day 180
Title
Plasma High Density Lipoprotein cholesterol (HDL-chol) dosage
Description
Determination of HDL-chol plasma concentration (mM) (a metabolic parameter), on fasted state
Time Frame
Day -14, Day 1, Day 42, Day 70, Day 111, Day 139, Day 180
Title
Plasma High Density Lipoprotein cholesterol (LDL-chol) calculation
Description
Determination of LDL-chol plasma concentration (mM) (metabolic parameter), on fasted state
Time Frame
Day -14, Day 1, Day 42, Day 70, Day 111, Day 139, Day 180
Title
Plasma Total Fatty Acids (FA) dosage
Description
Determination of total FA plasma concentration (mM) (a metabolic parameter), on fasted state
Time Frame
Day 1, Day 42, Day 70, Day 111, Day 139, Day 180
Title
Serum Insulin dosage
Description
Determination of insulin serum concentration (mU/L or pM) (a metabolic parameter), on fasted state
Time Frame
Day -14, Day 1, Day 42, Day 70, Day 111, Day 139, Day 180
Title
Weight measure
Description
the body weight (kg) will be recorded with a bathroom scale, on fasted state
Time Frame
Day -14, Day 1, Day 42, Day 70, Day 111, Day 139, Day 180
Title
Height measure
Description
the body height (cm) will be measured with a stadiometer.
Time Frame
Day -14
Title
Body Mass Index (BMI) calculation
Description
the BMI (kg/m²) will be calculated, on fasted state
Time Frame
Day -14, Day 1, Day 42, Day 70, Day 111, Day 139, Day 180
Title
Waist circumference measure
Description
the waist circumference (cm) will be recorded with a measuring tape, on fasted state
Time Frame
Day -14, Day 1, Day 42, Day 70, Day 111, Day 139, Day 180
Title
Fat mass ratio determination
Description
The percentage of fat mass (percent) (body composition) will be determined on each participant using a multi-frequency bioelectrical Impedance Analyzer, on fasted state
Time Frame
Day 1, Day 42, Day 70, Day 111, Day 139, Day 180
Title
Lean mass ratio determination
Description
The percentage of lean mass (percent) (body composition) will be determined on each participant using a multi-frequency bioelectrical Impedance Analyzer, on fasted state
Time Frame
Day 1, Day 42, Day 70, Day 111, Day 139, Day 180
Title
Water mass ratio determination
Description
The percentage of water (percent) (body composition) will be determined using a multi-frequency bioelectrical Impedance Analyzer, on fasted state
Time Frame
Day 1, Day 42, Day 70, Day 111, Day 139, Day 180
Title
RNA profiling on fasted state
Description
Nutrigenomic analysis will be performed from total Ribo Nucleic Acid (RNA) isolated blood collected in PAXgene Blood RNA Tube. The isolated RNA will be used to perform microarray analyses that allow identification of expression of all genes of the genome, on fasted state
Time Frame
Day 42, Day 111, Day 180
Title
RNA profiling on 6h post prandial state
Description
Analysis will be performed from total RNA isolated blood collected in PAXgene Blood RNA Tube. The isolated RNA will be used to perform microarray analyses that allow identification of expression of all genes of the genome, on post-prandial state 6h after the concomitant consumption of the study drink and challenge meal.
Time Frame
Day 42, Day 111, Day 180
Title
Gut microbiota profiling
Description
Identification of the microbiota composition of feces samples (collected by subjects) by performing a genetic sequencing analysis of bacterial DNA.
Time Frame
Day 1, Day 42, Day 70, Day 111, Day 139, Day 180
Title
Plasma carotenoids dosage
Description
Carotenoids will be quantitated from plasma (nM), on fasted state
Time Frame
Day 1, Day 42, Day 70, Day 111, Day 139, Day 180
Title
Plasma vitamine C dosage
Description
Vitamin C status will be quantified in deproteinized plasma (mg/L), on fasted state
Time Frame
Day 1, Day 42, Day 70, Day 111, Day 139, Day 180
Title
Treatment compliance
Description
Treatment compliance (percent) will be determined using counting of empty orange drinks brought back by volunteers after the consumption periods
Time Frame
Day 42, Day 111, Day 180
Title
Polyphenol intake
Description
Polyphenol intake (ml/day) in basal and during treatment consumption periods will be determined by a dietician using food report completed by volunteers.
Time Frame
Day 1, Day 42, Day 111, Day 180
Title
Low-polyphenol diet compliance
Description
Respect (y/n) of a low-polyphenol diet in basal (between Visit 1 - Visit 2) and during treatment consumption periods (between Visit 2 - Visit 3, Visit 4 - Visit 5, Visit 6 - Visit 7) will be determined by a dietician using 3 days food reports completed by volunteers.
Time Frame
Day 1, Day 42, Day 111, Day 180
Title
Calorie intake
Description
Calorie (kcal/day) intake in basal and during treatment consumption periods will be determined by a dietician using food report completed by volunteers.
Time Frame
Day 1, Day 42, Day 111, Day 180
Title
Protein intake
Description
Protein (g/day) intake in basal and during treatment consumption periods will be determined by a dietician using food report completed by volunteers.
Time Frame
Day 1, Day 42, Day 111, Day 180
Title
Lipid intake
Description
Lipid intake (g/day) in basal and during treatment consumption periods will be determined by a dietician using food report completed by volunteers.
Time Frame
Day 1, Day 42, Day 111, Day 180
Title
Carbohydrate intake
Description
Carbohydrate intake (g/day) in basal and during treatment consumption periods will be determined by a dietician using food report completed by volunteers.
Time Frame
Day 1, Day 42, Day 111, Day 180
Title
Diet division of protein/lipid/carbohydrate intakes
Description
The overall distribution of the protein/lipid/carbohydrate food intakes (%) will be determined by a dietician using food report completed by volunteers.
Time Frame
Day 1, Day 42, Day 111, Day 180
Title
Diet stability
Description
Diet stability (y/n) in terms of polyphenols, calories, proteins, carbohydrates and lipids intakes during the whole study will be determined by a dietician using the 4 food reports completed by volunteers.
Time Frame
Day 180
Title
Biobank for food metabolome
Description
Urine samples will be stored for further assessment of food metabolome to potentially identify new bioactive compounds present in the juice that could contribute to the biological response after orange juice/HESP intake.
Time Frame
Day -14, Day 1, Day 42, Day 70, Day 111, Day 139, Day 180
10. Eligibility
Sex
All
Minimum Age & Unit of Time
40 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Man or post-menopausal woman ;
40-65 years old (inclusive) ;
Body Mass Index (BMI)≤ 30 ;
Waist circumference ≥80 cm for women, and ≥94 cm for men ;
Weight > 46 kg
Normal biological balance sheet or considered normal by the investigator
No aversion or intolerance to citrus foods ;
Accept to limit their total intake of flavonoid rich beverages (tea, coffee, cocoa, wine, fruit juice) to 250 mL/day ;
Ability to give informed consent to participate in research ;
Willingness to accept randomization and undergo the testing and intervention procedures and deliver stool, blood and urine samples for testing ;
Affiliation to Social Security.
Exclusion Criteria:
Treated pre-diabetic or diabetic ;
Treated for hypertension ;
Use of statins or other medications for lowering cholesterol ;
Treated with antibiotics, antifungals, probiotics or prebiotics in the 3 months before the enrolment ;
Menopausal hormone replacement therapy ;
Diagnosed gastrointestinal illness in the judgement of the investigator ;
Any serious medical condition that precludes safe participation in the study, such as coronary artery disease, peripheral vascular disease, stroke, congestive heart failure, chronic obstructive pulmonary disease, insulin-dependent diabetes, psychiatric disease, renal disease, liver disease, active cancer and anemia ;
History of eating disorders such as bulimia nervosa, anorexia nervosa and severe binge eating disorder in the last 5 years ;
Digestive disorders with diarrhea during the 3 months preceding the beginning of the study ;
Self-declared vegetarian, vegetalian, vegan ;
History of substance abuse or alcohol abuse ;
Involvement in a weight loss intervention program (including anti-obesity medication) within the past 3 months or who have had bariatric surgery ;
Current smokers (within the last 30 days) ;
Use of dietary supplements (vitamins, antioxidants) currently or in the past one month ;
Strenuous exercise greater than 6 hours per week ;
Anyone who in the opinion of the investigator is unlikely to be able to comply with the protocol ;
Subjects involved in another clinical trial or being in the exclusion period of another study or having received a total compensation greater than 4,500 euros over the 12 months preceding the start of the trial ;
Subject benefiting from a legal protection measure (curatorship, guardianship, safeguard of justice) ;
Refusal to participate.
Facility Information:
Facility Name
University Hospital, Clermont Ferrand
City
Clermont-Ferrand
State/Province
Aura
ZIP/Postal Code
63000
Country
France
12. IPD Sharing Statement
Citations:
PubMed Identifier
34848522
Citation
Verny MA, Milenkovic D, Macian N, Pereira B, Evrard R, Gilcher C, Steingass CB, Mosoni P, Gladine C, Monfoulet LE, Schweiggert R, Pickering G, Morand C. Evaluating the role of orange juice, HESPERidin in vascular HEALTH benefits (HESPER-HEALTH study): protocol for a randomised controlled trial. BMJ Open. 2021 Nov 30;11(11):e053321. doi: 10.1136/bmjopen-2021-053321.
Results Reference
derived
Learn more about this trial
Orange Juice, Hesperidin and Their Role in Vascular Health Benefit
We'll reach out to this number within 24 hrs