Back to resultsEffects of L-citrulline Supplementation on Vascular Function in Metabolic Syndrome
Primary Purpose
Metabolic Syndrome, Menopause
Status
Recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
L-Citrulline supplementation
Placebo
Sponsored by
About this trial
This is an interventional basic science trial for Metabolic Syndrome focused on measuring Endothelial function, Aortic Hemodynamics, Blood pressure, Obesity, Hypertension
Eligibility Criteria
Inclusion Criteria: Must present at least 3 of the following 5 cardiometabolic risk factors Waist circumference ≥88 cm Fasting glucose between 100-125 mg/dL or HbA1c between 5.7-6.4%. Blood pressure ≥130 mm Hg Triglyceride ≥ 150 mg/dL HDL <50 mg/dL The following are also inclusion criteria's: Women aged 45-79 years old Body mass index ≤ 39.9 kg/m2 Sedentary (defined as < 120 min/week of exercise) Abstain from any dietary supplements with vascular effects for one month prior to the beginning of the study and until participation in study has terminated. Exclusion Criteria: < 45 and > 79 years of age Use of medications and/or any supplements that may affect outcome variables (such as arginine-containing supplements, nitroglycerin, statin drugs, biguanides, insulin, beta blockers, statins, verapamil) Systolic blood pressure ≥ 160 mmHg BMI > 40 kg/m2 Recent changes in medication (3 months) Current smoking any tobacco use Cardiovascular disease, diabetes (Type 1 or 2), and other metabolic or chronic diseases More than 7 alcoholic drinks/week of consumption
Sites / Locations
- TTU Kinesiology and Sport Management BuildingRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
L-citrulline
Placebo
Arm Description
L-citrulline: 10 grams/day
Microcrystalline Cellulose
Outcomes
Primary Outcome Measures
Macrovascular Endothelial function in the fasted condition
Endothelial function will be measured via brachial artery flow mediated dilation (ultrasonography) during reactive hyperemia at baseline and after 4 weeks of supplementation.
Microvascular endothelial function in the fasted condition
Endothelial function will be measured using forearm muscle oxygenation (near-infrared spectroscopy) will assessed during reactive hyperemia at baseline and after 4 weeks of supplementation.
Microvascular digital endothelial function in the fasted condition
Endothelial function will be measured using peripheral (finger) arterial tonometry (EndoPAT device) during reactive hyperemia at baseline and after 4 weeks of supplementation.
Macrovascular Endothelial function during acute hyperglycemia
Endothelial function will be measured via brachial artery flow mediated dilation (ultrasonography) during reactive hyperemia at 30, 60, and 90 minutes after oral glucose ingestion at baseline and after 4 weeks of supplementation.
Microvascular forearm endothelial function during acute hyperglycemia
Endothelial function will be measured using forearm muscle oxygenation (near-infrared spectroscopy) during reactive hyperemia at 30, 60, and 90 minutes after oral glucose ingestion at baseline and after 4 weeks of supplementation.
Central and peripheral arterial stiffness in the fasted condition
Arterial stiffness will be measured using central (carotid-femoral) and peripheral (femoral-ankle) PWV at baseline and after 4 weeks of supplementation.
Central arterial stiffness during acute hyperglycemia
Arterial stiffness will be measured using central (carotid-femoral) PWV at 30, 60, and 90 minutes after oral glucose ingestion at baseline and after 4 weeks of supplementation.
Blood pressure in the fasted condition
Brachial and aortic blood pressures will be assessed using an automated sphygmomanometry arm cuff (SphygmoCor XCEL). Beat-to-beat blood pressure will be measured using an automated photoplethysmography finger cuff (Fineometer). Blood pressure will be measured at baseline and after 4 weeks of supplementation.
Blood pressure during acute hyperglycemia
Brachial and aortic blood pressures (systolic and diastolic) will be assessed using an automated sphygmomanometry arm cuff (SphygmoCor XCEL). Beat-to-beat blood pressure will be measured using an automated photoplethysmography finger cuff (Fineometer). Blood pressure will be measured after an oral glucose ingestion at 30, 60, and 90 minutes at baseline and after 4 weeks of supplementation.
Total peripheral resistance in the fasted condition.
Total peripheral resistance will be measured using an automated photoplethysmography finger cuff (Finometer) at baseline and after 4 weeks of supplementation.
Total peripheral resistance during acute hyperglycemia
Total peripheral resistance will be measured using an automated photoplethysmography finger cuff (Finometer) at 30, 60, and 90 minutes after oral glucose ingestion at baseline and after 4 weeks of supplementation.
Stroke volume in the fasted condition
Stroke volume will be measured using an automated photoplethysmography finger cuff (Finometer) at baseline and after 4 weeks of supplementation.
Stroke volume during acute hyperglycemia
Stroke volume will be measured using an automated photoplethysmography finger cuff (Finometer) at 30, 60, and 90 minutes after oral glucose ingestion at baseline and after 4 weeks of supplementation.
24-hour ambulatory blood pressure monitoring
An ambulatory blood pressure cuff, measuring blood pressure for 24-hours will be obtained on two separate days at baseline and after 4 weeks of supplementation.
Secondary Outcome Measures
Serum glucose and insulin levels.
Serum glucose and insulin levels will be tested at baseline and after 4 weeks of supplementation.
Serum arginine levels
Serum L-Arginine levels will be tested at baseline and after 4 weeks of supplementation.
Serum arginase levels
Serum arginase levels will be tested at baseline and after 4 weeks of supplementation.
Serum Nitric Oxide levels
Serum nitric oxide levels will be tested at baseline and after 4 weeks of supplementation.
Serum Endothelin-1 levels
Serum endothelin-1 levels will be tested at baseline and after 4 weeks of supplementation.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT06025357
Brief Title
Effects of L-citrulline Supplementation on Vascular Function in Metabolic Syndrome
Official Title
Effects of L-Citrulline Supplementation on Vascular Function During Fasted and Acute Hyperglycemia in Middle-aged and Older Women With Metabolic Syndrome
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
January 1, 2023 (Actual)
Primary Completion Date
May 1, 2024 (Anticipated)
Study Completion Date
August 1, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Texas Tech University
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
The objective of this project is to provide evidence that L-Citrulline (CIT) supplementation can improve vascular function in the fasted and acute hyperglycemia conditions in middle-aged and older women with metabolic syndrome.
Detailed Description
Using a double-blind, randomized, placebo-controlled, and parallel design, middle-aged and older women with metabolic syndrome will be randomized into receiving either CIT supplementation (10g/day) or placebo (Microcrystalline Cellulose) for 4 weeks.
The first visit will be approximately 1hr and 30 minutes. The 2nd and 3rd visits will each be approximately 2hrs and 30 minutes, separated by 4 weeks in between each visit. During visits 2 and 3, vascular measurements will be assessed in the fasted state and 30, 60, and 90 minutes after acute glucose ingestion (75g).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metabolic Syndrome, Menopause
Keywords
Endothelial function, Aortic Hemodynamics, Blood pressure, Obesity, Hypertension
7. Study Design
Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
Parallel Assignment Double (Participant, Investigator) Randomized, double-blind, placebo-controlled, parallel study design
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
24 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
L-citrulline
Arm Type
Experimental
Arm Description
L-citrulline: 10 grams/day
Arm Title
Placebo
Arm Type
Experimental
Arm Description
Microcrystalline Cellulose
Intervention Type
Dietary Supplement
Intervention Name(s)
L-Citrulline supplementation
Intervention Description
4 weeks of L-Citrulline supplementation (10 grams/day).
Intervention Type
Dietary Supplement
Intervention Name(s)
Placebo
Intervention Description
4 weeks of microcrystalline Cellulose supplementation.
Primary Outcome Measure Information:
Title
Macrovascular Endothelial function in the fasted condition
Description
Endothelial function will be measured via brachial artery flow mediated dilation (ultrasonography) during reactive hyperemia at baseline and after 4 weeks of supplementation.
Time Frame
4 weeks
Title
Microvascular endothelial function in the fasted condition
Description
Endothelial function will be measured using forearm muscle oxygenation (near-infrared spectroscopy) will assessed during reactive hyperemia at baseline and after 4 weeks of supplementation.
Time Frame
4 weeks
Title
Microvascular digital endothelial function in the fasted condition
Description
Endothelial function will be measured using peripheral (finger) arterial tonometry (EndoPAT device) during reactive hyperemia at baseline and after 4 weeks of supplementation.
Time Frame
4 weeks
Title
Macrovascular Endothelial function during acute hyperglycemia
Description
Endothelial function will be measured via brachial artery flow mediated dilation (ultrasonography) during reactive hyperemia at 30, 60, and 90 minutes after oral glucose ingestion at baseline and after 4 weeks of supplementation.
Time Frame
4 weeks
Title
Microvascular forearm endothelial function during acute hyperglycemia
Description
Endothelial function will be measured using forearm muscle oxygenation (near-infrared spectroscopy) during reactive hyperemia at 30, 60, and 90 minutes after oral glucose ingestion at baseline and after 4 weeks of supplementation.
Time Frame
4 weeks
Title
Central and peripheral arterial stiffness in the fasted condition
Description
Arterial stiffness will be measured using central (carotid-femoral) and peripheral (femoral-ankle) PWV at baseline and after 4 weeks of supplementation.
Time Frame
4 weeks
Title
Central arterial stiffness during acute hyperglycemia
Description
Arterial stiffness will be measured using central (carotid-femoral) PWV at 30, 60, and 90 minutes after oral glucose ingestion at baseline and after 4 weeks of supplementation.
Time Frame
4 weeks
Title
Blood pressure in the fasted condition
Description
Brachial and aortic blood pressures will be assessed using an automated sphygmomanometry arm cuff (SphygmoCor XCEL). Beat-to-beat blood pressure will be measured using an automated photoplethysmography finger cuff (Fineometer). Blood pressure will be measured at baseline and after 4 weeks of supplementation.
Time Frame
4 weeks
Title
Blood pressure during acute hyperglycemia
Description
Brachial and aortic blood pressures (systolic and diastolic) will be assessed using an automated sphygmomanometry arm cuff (SphygmoCor XCEL). Beat-to-beat blood pressure will be measured using an automated photoplethysmography finger cuff (Fineometer). Blood pressure will be measured after an oral glucose ingestion at 30, 60, and 90 minutes at baseline and after 4 weeks of supplementation.
Time Frame
4 weeks
Title
Total peripheral resistance in the fasted condition.
Description
Total peripheral resistance will be measured using an automated photoplethysmography finger cuff (Finometer) at baseline and after 4 weeks of supplementation.
Time Frame
4 weeks
Title
Total peripheral resistance during acute hyperglycemia
Description
Total peripheral resistance will be measured using an automated photoplethysmography finger cuff (Finometer) at 30, 60, and 90 minutes after oral glucose ingestion at baseline and after 4 weeks of supplementation.
Time Frame
4 weeks
Title
Stroke volume in the fasted condition
Description
Stroke volume will be measured using an automated photoplethysmography finger cuff (Finometer) at baseline and after 4 weeks of supplementation.
Time Frame
4 weeks
Title
Stroke volume during acute hyperglycemia
Description
Stroke volume will be measured using an automated photoplethysmography finger cuff (Finometer) at 30, 60, and 90 minutes after oral glucose ingestion at baseline and after 4 weeks of supplementation.
Time Frame
4 weeks
Title
24-hour ambulatory blood pressure monitoring
Description
An ambulatory blood pressure cuff, measuring blood pressure for 24-hours will be obtained on two separate days at baseline and after 4 weeks of supplementation.
Time Frame
4 weeks
Secondary Outcome Measure Information:
Title
Serum glucose and insulin levels.
Description
Serum glucose and insulin levels will be tested at baseline and after 4 weeks of supplementation.
Time Frame
4 weeks
Title
Serum arginine levels
Description
Serum L-Arginine levels will be tested at baseline and after 4 weeks of supplementation.
Time Frame
4 weeks
Title
Serum arginase levels
Description
Serum arginase levels will be tested at baseline and after 4 weeks of supplementation.
Time Frame
4 weeks
Title
Serum Nitric Oxide levels
Description
Serum nitric oxide levels will be tested at baseline and after 4 weeks of supplementation.
Time Frame
4 weeks
Title
Serum Endothelin-1 levels
Description
Serum endothelin-1 levels will be tested at baseline and after 4 weeks of supplementation.
Time Frame
4 weeks
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
45 Years
Maximum Age & Unit of Time
79 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Must present at least 3 of the following 5 cardiometabolic risk factors
Waist circumference ≥88 cm
Fasting glucose between 100-125 mg/dL or HbA1c between 5.7-6.4%.
Blood pressure ≥130 mm Hg
Triglyceride ≥ 150 mg/dL
HDL <50 mg/dL
The following are also inclusion criteria's:
Women aged 45-79 years old
Body mass index ≤ 39.9 kg/m2
Sedentary (defined as < 120 min/week of exercise)
Abstain from any dietary supplements with vascular effects for one month prior to the beginning of the study and until participation in study has terminated.
Exclusion Criteria:
< 45 and > 79 years of age
Use of medications and/or any supplements that may affect outcome variables (such as arginine-containing supplements, nitroglycerin, statin drugs, biguanides, insulin, beta blockers, statins, verapamil)
Systolic blood pressure ≥ 160 mmHg
BMI > 40 kg/m2
Recent changes in medication (3 months)
Current smoking any tobacco use
Cardiovascular disease, diabetes (Type 1 or 2), and other metabolic or chronic diseases
More than 7 alcoholic drinks/week of consumption
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Arturo Figueroa, Ph.D,MD
Phone
806-834-5587
Email
arturo.figueroa@ttu.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Arturo Figueroa
Organizational Affiliation
Texas Tech University
Official's Role
Principal Investigator
Facility Information:
Facility Name
TTU Kinesiology and Sport Management Building
City
Lubbock
State/Province
Texas
ZIP/Postal Code
79409
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Arturo Figueroa, M.D., Ph.D.
Phone
806-834-5587
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
37049398
Citation
Figueroa A, Maharaj A, Kang Y, Dillon KN, Martinez MA, Morita M, Nogimura D, Fischer SM. Combined Citrulline and Glutathione Supplementation Improves Endothelial Function and Blood Pressure Reactivity in Postmenopausal Women. Nutrients. 2023 Mar 23;15(7):1557. doi: 10.3390/nu15071557.
Results Reference
background
PubMed Identifier
34974502
Citation
Maharaj A, Fischer SM, Dillon KN, Kang Y, Martinez MA, Figueroa A. Acute Citrulline Blunts Aortic Systolic Pressure during Exercise and Sympathoactivation in Hypertensive Postmenopausal Women. Med Sci Sports Exerc. 2022 May 1;54(5):761-768. doi: 10.1249/MSS.0000000000002848. Epub 2022 Jan 3.
Results Reference
background
PubMed Identifier
30412905
Citation
McDonald JD, Mah E, Chitchumroonchokchai C, Dey P, Labyk AN, Villamena FA, Volek JS, Bruno RS. Dairy milk proteins attenuate hyperglycemia-induced impairments in vascular endothelial function in adults with prediabetes by limiting increases in glycemia and oxidative stress that reduce nitric oxide bioavailability. J Nutr Biochem. 2019 Jan;63:165-176. doi: 10.1016/j.jnutbio.2018.09.018. Epub 2018 Sep 25.
Results Reference
background
PubMed Identifier
25636814
Citation
Figueroa A, Alvarez-Alvarado S, Ormsbee MJ, Madzima TA, Campbell JC, Wong A. Impact of L-citrulline supplementation and whole-body vibration training on arterial stiffness and leg muscle function in obese postmenopausal women with high blood pressure. Exp Gerontol. 2015 Mar;63:35-40. doi: 10.1016/j.exger.2015.01.046. Epub 2015 Jan 28.
Results Reference
background
PubMed Identifier
36297080
Citation
Maharaj A, Fischer SM, Dillon KN, Kang Y, Martinez MA, Figueroa A. Effects of L-Citrulline Supplementation on Endothelial Function and Blood Pressure in Hypertensive Postmenopausal Women. Nutrients. 2022 Oct 20;14(20):4396. doi: 10.3390/nu14204396.
Results Reference
result
Learn more about this trial
Effects of L-citrulline Supplementation on Vascular Function in Metabolic Syndrome
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