Back to resultsResveratrol for the Treatment of Non Alcoholic Fatty Liver Disease and Insulin Resistance in Overweight Adolescents
Primary Purpose
NAFLD, TYPE 2 DIABETES, METABOLIC SYNDROME
Status
Completed
Phase
Phase 2
Locations
Canada
Study Type
Interventional
Intervention
Resveratrol
Placebo
Sponsored by
About this trial
This is an interventional prevention trial for NAFLD focused on measuring Pediatrics, Adolescents, NAFLD, Spectroscopy, Type 2 diabetes
Eligibility Criteria
Inclusion Criteria:
- 13 to <18 years of age
- BMI considered overweight (BMI > 25 kg/m2 ) or obese (BMI > 30 kg/m2 )
- Confirmed 1H-MRS defined hepatic steatosis (>5.5% fat/water)
- Parent/Guardian willing and able to provide written, signed informed consent, and subjects willing to co-sign parental consent
- Sexually active subjects must be willing to use an acceptable method of contraception
- Females of child bearing potential must have a negative pregnancy test at screening.
Exclusion Criteria:
- The use of any chronic medications with the exception of oral birth control and natural health products with the exception of multivitamins.
- Adolescents with altered insulin sensitivity or tissue lipid content unrelated to obesity and the metabolic syndrome, including:
type 2 diabetes; present or previous malignancy renal disease, hypertension (anyone who has BPs over the 99th percentile for age and gender) or liver disease;
- significant weight loss (10% in last six months) or enrolled in weight loss program in the six months prior to the study;
- self-reported history of alcohol consumption of greater than two drinks per day and/or drinking alcohol more than once weekly;
- report using non-prescription recreational drugs;
- allergies or sensitivities to any of the ingredients in the investigational product or placebo;
- females breastfeeding at screening or planning on becoming pregnant at any time during the study;
Sites / Locations
- Children's Hospital Research Institute of Manitoba/University of Manitoba
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Resveratrol
Placebo
Arm Description
Intervention: Resveratrol Oral supplementation of resveratrol (ResVida) 75 mg twice daily (with breakfast and dinner) for a total daily dose of 150 mg for the duration of 30 days.
Intervention: Placebo Control Oral supplementation of placebo twice daily (with breakfast and dinner) for a total duration of 30 days.
Outcomes
Primary Outcome Measures
Safety/ Adverse Event Outcome
Primary Side effect profile determined by participant interview and serum biochemistry. Side effect profile determined by serum biochemistry: AST, ALT, total and conjugated bilirubin, Creatinine, sodium, potassium, calcium, magnesium, chloride and TC02, haemoglobin, haematocrit, white blood cell and platelet counts, erythrocytes, and fasting lipid levels (total cholesterol, HDL-cholesterol, LDL-cholesterol and triglycerides). Fasting glucose and insulin levels. PT/INR and PTT levels.
Vital signs
Safety/ Adverse Event Outcome
Primary Side effect profile determined by participant interview. Side effect profile determined by serum biochemistry: AST, ALT, total and conjugated bilirubin, Creatinine, sodium, potassium, calcium, magnesium, chloride and TC02, haemoglobin, haematocrit, white blood cell and platelet counts, erythrocytes, and fasting lipid levels (total cholesterol, HDL-cholesterol, LDL-cholesterol and triglycerides). Fasting glucose and insulin levels. PT/INR and PTT levels.
Vital signs
Safety/ Adverse Event Outcome
Primary Side effect profile determined by participant interview. Side effect profile determined by serum biochemistry: AST, ALT, total and conjugated bilirubin, Creatinine, sodium, potassium, calcium, magnesium, chloride and TC02, haemoglobin, haematocrit, white blood cell and platelet counts, erythrocytes, and fasting lipid levels (total cholesterol, HDL-cholesterol, LDL-cholesterol and triglycerides). Fasting glucose and insulin levels. PT/INR and PTT levels.
Vital signs
Safety/ Adverse Event Outcome
Primary Side effect profile determined by participant interview. Side effect profile determined by serum biochemistry: AST, ALT, total and conjugated bilirubin, Creatinine, sodium, potassium, calcium, magnesium, chloride and TC02, haemoglobin, haematocrit, white blood cell and platelet counts, erythrocytes, and fasting lipid levels (total cholesterol, HDL-cholesterol, LDL-cholesterol and triglycerides). Fasting glucose and insulin levels. PT/INR and PTT levels.
Vital signs
Safety/ Adverse Event Outcome
Primary Side effect profile determined by participant interview. Side effect profile determined by serum biochemistry: AST, ALT, total and conjugated bilirubin, Creatinine, sodium, potassium, calcium, magnesium, chloride and TC02, haemoglobin, haematocrit, white blood cell and platelet counts, erythrocytes, and fasting lipid levels (total cholesterol, HDL-cholesterol, LDL-cholesterol and triglycerides). Fasting glucose and insulin levels. PT/INR and PTT levels.
Vital signs
Efficacy Outcome
To determine efficacy of resveratrol to reduce hepatic and cardiac triglyceride content in adolescents with NAFL MR spectroscopy will be performed using a 3.0-Tesla whole-body magnet. Sixty-four spectra will be acquired and averaged for the determination of intracellular water and lipid content. LCModel software will be used to isolate and quantify lipid and water peaks. Hepatic steatosis will be defined as hepatic triglyceride content of >.5% fat/water.
Secondary Outcome Measures
Efficacy Outcome
To determine efficacy of resveratrol to reduce whole body insulin resistance in overweight and obese adolescents with NAFL. The 3-hr frequently sampled oral glucose tolerance test (OGTT) using a standard 75-gram-glucose-load will be performed at the baseline visit and after completion of supplementation (day 30; visit 3). Blood samples will be collected at 20, 30, 60, 90, 120 and 180 minutes after ingestion of glucose will be used for the determination of insulin sensitivity using the Matsuda index
Efficacy Outcome
To determine the effects of resveratrol on cardiac function and morphology in the study population. Cardiac function and morphology will be measured using a cardiac ultrasound at baseline (day 0) and at completion of supplementation (day 30; visit 3).
Efficacy Outcome
To determine the effect of resveratrol supplementation on serum markers of inflammation. Inflammatory markers will be assessed by measurements of circulating adiponectin, leptin, CRP, ESR, TNFalpha, IL-1beta, IL-6, and IL-10, using commercially available ELISA assays.
Efficacy Outcome
To determine the effect of resveratrol supplementation on serum markers of inflammation. Inflammatory markers will be assessed by measurements of circulating adiponectin, leptin, CRP, ESR, TNFalpha, IL-1beta, IL-6, and IL-10, using commercially available ELISA assays.
Efficacy Outcome
To determine the effect of resveratrol supplementation on serum markers of inflammation. Inflammatory markers will be assessed by measurements of circulating adiponectin, leptin, CRP, ESR, TNFalpha, IL-1beta, IL-6, and IL-10, using commercially available ELISA assays
Efficacy Outcome
To determine the effect of resveratrol supplementation on serum markers of inflammation. Inflammatory markers will be assessed by measurements of circulating adiponectin, leptin, CRP, ESR, TNFalpha, IL-1beta, IL-6, and IL-10, using commercially available ELISA assays
Full Information
NCT ID
NCT02216552
First Posted
August 12, 2014
Last Updated
May 2, 2017
Sponsor
University of Manitoba
Collaborators
DSM Nutritional Products, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT02216552
Brief Title
Resveratrol for the Treatment of Non Alcoholic Fatty Liver Disease and Insulin Resistance in Overweight Adolescents
Official Title
Safety and Efficacy of Resveratrol for the Treatment of Non-Alcoholic Fatty Liver Disease and Associated Insulin Resistance in Overweight and Obese Adolescents
Study Type
Interventional
2. Study Status
Record Verification Date
May 2017
Overall Recruitment Status
Completed
Study Start Date
August 2015 (undefined)
Primary Completion Date
January 1, 2017 (Actual)
Study Completion Date
March 20, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Manitoba
Collaborators
DSM Nutritional Products, Inc.
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The current project is designed as a 30-day pilot trial to demonstrate the safety and tolerability of resveratrol therapy in overweight adolescents to decrease liver fat, and improve insulin sensitivity to prevent type 2 diabetes.
Detailed Description
Pilot study of 10 overweight or obese children with MRS determined fatty liver randomized to resveratrol or placebo. Primary outcome measures include change in liver triglyceride content as determined by MRS and improvement in insulin resistance as determined by the area under the curve of glucose excursion during a 75 gram oral glucose tolerance test.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
NAFLD, TYPE 2 DIABETES, METABOLIC SYNDROME
Keywords
Pediatrics, Adolescents, NAFLD, Spectroscopy, Type 2 diabetes
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Model Description
Resveratrol as ResVida (TM) compared to a placebo
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
10 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Resveratrol
Arm Type
Experimental
Arm Description
Intervention: Resveratrol Oral supplementation of resveratrol (ResVida) 75 mg twice daily (with breakfast and dinner) for a total daily dose of 150 mg for the duration of 30 days.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Intervention: Placebo Control Oral supplementation of placebo twice daily (with breakfast and dinner) for a total duration of 30 days.
Intervention Type
Dietary Supplement
Intervention Name(s)
Resveratrol
Other Intervention Name(s)
ResVida (Registered Trademark of DSM)
Intervention Description
All adolescents will receive standardized lifestyle counselling at enrolment designed and disseminated by a registered dietitian as well as a licensed physiotherapist who both have experience working with overweight adolescents. The lifestyle component will be goal-based and tailored to each participant. The overall content and messaging will be consistent for all participants with nutritional recommendations based on Canada Food Guide and physical activity counselling aligning with the Healthy Active Living Recommendations of the Canadian Pediatric Society and Health Canada's Physical Activity Guidelines.
Intervention Type
Dietary Supplement
Intervention Name(s)
Placebo
Intervention Description
All adolescents will receive standardized lifestyle counselling at enrolment designed and disseminated by a registered dietitian as well as a licensed physiotherapist who both have experience working with overweight adolescents. The lifestyle component will be goal-based and tailored to each participant. The overall content and messaging will be consistent for all participants with nutritional recommendations based on Canada Food Guide and physical activity counselling aligning with the Healthy Active Living Recommendations of the Canadian Pediatric Society and Health Canada's Physical Activity Guidelines.
Primary Outcome Measure Information:
Title
Safety/ Adverse Event Outcome
Description
Primary Side effect profile determined by participant interview and serum biochemistry. Side effect profile determined by serum biochemistry: AST, ALT, total and conjugated bilirubin, Creatinine, sodium, potassium, calcium, magnesium, chloride and TC02, haemoglobin, haematocrit, white blood cell and platelet counts, erythrocytes, and fasting lipid levels (total cholesterol, HDL-cholesterol, LDL-cholesterol and triglycerides). Fasting glucose and insulin levels. PT/INR and PTT levels.
Vital signs
Time Frame
One week
Title
Safety/ Adverse Event Outcome
Description
Primary Side effect profile determined by participant interview. Side effect profile determined by serum biochemistry: AST, ALT, total and conjugated bilirubin, Creatinine, sodium, potassium, calcium, magnesium, chloride and TC02, haemoglobin, haematocrit, white blood cell and platelet counts, erythrocytes, and fasting lipid levels (total cholesterol, HDL-cholesterol, LDL-cholesterol and triglycerides). Fasting glucose and insulin levels. PT/INR and PTT levels.
Vital signs
Time Frame
Week 2
Title
Safety/ Adverse Event Outcome
Description
Primary Side effect profile determined by participant interview. Side effect profile determined by serum biochemistry: AST, ALT, total and conjugated bilirubin, Creatinine, sodium, potassium, calcium, magnesium, chloride and TC02, haemoglobin, haematocrit, white blood cell and platelet counts, erythrocytes, and fasting lipid levels (total cholesterol, HDL-cholesterol, LDL-cholesterol and triglycerides). Fasting glucose and insulin levels. PT/INR and PTT levels.
Vital signs
Time Frame
Week 3
Title
Safety/ Adverse Event Outcome
Description
Primary Side effect profile determined by participant interview. Side effect profile determined by serum biochemistry: AST, ALT, total and conjugated bilirubin, Creatinine, sodium, potassium, calcium, magnesium, chloride and TC02, haemoglobin, haematocrit, white blood cell and platelet counts, erythrocytes, and fasting lipid levels (total cholesterol, HDL-cholesterol, LDL-cholesterol and triglycerides). Fasting glucose and insulin levels. PT/INR and PTT levels.
Vital signs
Time Frame
Week 4
Title
Safety/ Adverse Event Outcome
Description
Primary Side effect profile determined by participant interview. Side effect profile determined by serum biochemistry: AST, ALT, total and conjugated bilirubin, Creatinine, sodium, potassium, calcium, magnesium, chloride and TC02, haemoglobin, haematocrit, white blood cell and platelet counts, erythrocytes, and fasting lipid levels (total cholesterol, HDL-cholesterol, LDL-cholesterol and triglycerides). Fasting glucose and insulin levels. PT/INR and PTT levels.
Vital signs
Time Frame
Week 8
Title
Efficacy Outcome
Description
To determine efficacy of resveratrol to reduce hepatic and cardiac triglyceride content in adolescents with NAFL MR spectroscopy will be performed using a 3.0-Tesla whole-body magnet. Sixty-four spectra will be acquired and averaged for the determination of intracellular water and lipid content. LCModel software will be used to isolate and quantify lipid and water peaks. Hepatic steatosis will be defined as hepatic triglyceride content of >.5% fat/water.
Time Frame
Week 4
Secondary Outcome Measure Information:
Title
Efficacy Outcome
Description
To determine efficacy of resveratrol to reduce whole body insulin resistance in overweight and obese adolescents with NAFL. The 3-hr frequently sampled oral glucose tolerance test (OGTT) using a standard 75-gram-glucose-load will be performed at the baseline visit and after completion of supplementation (day 30; visit 3). Blood samples will be collected at 20, 30, 60, 90, 120 and 180 minutes after ingestion of glucose will be used for the determination of insulin sensitivity using the Matsuda index
Time Frame
Week 4
Title
Efficacy Outcome
Description
To determine the effects of resveratrol on cardiac function and morphology in the study population. Cardiac function and morphology will be measured using a cardiac ultrasound at baseline (day 0) and at completion of supplementation (day 30; visit 3).
Time Frame
Week 4
Title
Efficacy Outcome
Description
To determine the effect of resveratrol supplementation on serum markers of inflammation. Inflammatory markers will be assessed by measurements of circulating adiponectin, leptin, CRP, ESR, TNFalpha, IL-1beta, IL-6, and IL-10, using commercially available ELISA assays.
Time Frame
Week 1
Title
Efficacy Outcome
Description
To determine the effect of resveratrol supplementation on serum markers of inflammation. Inflammatory markers will be assessed by measurements of circulating adiponectin, leptin, CRP, ESR, TNFalpha, IL-1beta, IL-6, and IL-10, using commercially available ELISA assays.
Time Frame
Week 2
Title
Efficacy Outcome
Description
To determine the effect of resveratrol supplementation on serum markers of inflammation. Inflammatory markers will be assessed by measurements of circulating adiponectin, leptin, CRP, ESR, TNFalpha, IL-1beta, IL-6, and IL-10, using commercially available ELISA assays
Time Frame
Week 3
Title
Efficacy Outcome
Description
To determine the effect of resveratrol supplementation on serum markers of inflammation. Inflammatory markers will be assessed by measurements of circulating adiponectin, leptin, CRP, ESR, TNFalpha, IL-1beta, IL-6, and IL-10, using commercially available ELISA assays
Time Frame
Week 4
10. Eligibility
Sex
All
Minimum Age & Unit of Time
13 Years
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
13 to <18 years of age
BMI considered overweight (BMI > 25 kg/m2 ) or obese (BMI > 30 kg/m2 )
Confirmed 1H-MRS defined hepatic steatosis (>5.5% fat/water)
Parent/Guardian willing and able to provide written, signed informed consent, and subjects willing to co-sign parental consent
Sexually active subjects must be willing to use an acceptable method of contraception
Females of child bearing potential must have a negative pregnancy test at screening.
Exclusion Criteria:
The use of any chronic medications with the exception of oral birth control and natural health products with the exception of multivitamins.
Adolescents with altered insulin sensitivity or tissue lipid content unrelated to obesity and the metabolic syndrome, including:
type 2 diabetes; present or previous malignancy renal disease, hypertension (anyone who has BPs over the 99th percentile for age and gender) or liver disease;
significant weight loss (10% in last six months) or enrolled in weight loss program in the six months prior to the study;
self-reported history of alcohol consumption of greater than two drinks per day and/or drinking alcohol more than once weekly;
report using non-prescription recreational drugs;
allergies or sensitivities to any of the ingredients in the investigational product or placebo;
females breastfeeding at screening or planning on becoming pregnant at any time during the study;
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Brandy A Wicklow, MD, MSc
Organizational Affiliation
University of Manitoba
Official's Role
Principal Investigator
Facility Information:
Facility Name
Children's Hospital Research Institute of Manitoba/University of Manitoba
City
Winnipeg
State/Province
Manitoba
ZIP/Postal Code
R3E 3P4
Country
Canada
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Resveratrol for the Treatment of Non Alcoholic Fatty Liver Disease and Insulin Resistance in Overweight Adolescents
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