title: Proposed trial: safety and efficacy of resveratrol for the treatment of non-alcoholic fatty liver disease (NAFLD) and associated insulin resistance in adolescents who are overweight or obese adolescents - rationale and protocol.
abstract: Non-alcoholic fatty liver (NAFL) disease (NAFLD) affects 30% of overweight adolescents and increases the risk of type 2 diabetes mellitus (T2D). Resveratrol is a naturally occurring compound with potential to reverse NAFL and its associated insulin resistance in adults. The use of resveratrol to reduce risk for T2D through its effect on NAFL has not been examined to date in youth. This paper provides a literature review and protocol for a 30 day proof of principle trial of resveratrol in a population of adolescents at risk for T2D. This randomized double-blind controlled trial is designed with the primary objective of evaluating a twice daily supplementation of 75 mg of resveratrol for safety and tolerability in overweight and obese adolescent subjects (13 to <18 years of age) with NAFL. Secondary objectives are to determine the effect size of the intervention on hepatic steatosis and whole body insulin sensitivity. Adolescents in the intervention arm (n = 10) will receive oral supplementation of resveratrol 75 mg twice daily (with breakfast and dinner) for a total daily dose of 150 mg for the duration of 30 days. The comparison group (n = 10) will receive a placebo twice daily for 30 days. Both cases and controls will receive a standardized lifestyle intervention program. Subjects in both groups will be followed for an additional 30 days post intervention for total study duration of approximately 60 days. Primary outcome measures include a primary side effect profile determined by participant interview, a side effect profile determined by serum biochemistry and vital signs. Secondary outcome measures include an oral glucose tolerance test, liver and cardiac fat content measured by magnetic resonance spectroscopy, anthropometric measures of overweight/obesity, inflammatory markers, and cardiac function and morphology measured with ultrasonography. Additional outcome measures include serum concentrations of resveratrol, compliance to protocol, physical activity, and nutritional assessment. This study will determine the safety and tolerability of resveratrol in an overweight adolescent population and inform the design of a larger randomized controlled trial.
authors: a Pediatrics and Child Health, University of Manitoba, MB, Canada.|b The Manitoba Institute of Child Health: Diabetes Research Envisioned and Accomplished in Manitoba (DREAM) Theme, MB, Canada.
authors: Brandy
authors: B
authors: Wicklow
authors: a Pediatrics and Child Health, University of Manitoba, MB, Canada.|b The Manitoba Institute of Child Health: Diabetes Research Envisioned and Accomplished in Manitoba (DREAM) Theme, MB, Canada.|c Center for Health Care Innovation, MB, Canada.|d Winnipeg Regional Health Authority, MB, Canada.
authors: Kristy
authors: K
authors: Wittmeier
authors: a Pediatrics and Child Health, University of Manitoba, MB, Canada.|b The Manitoba Institute of Child Health: Diabetes Research Envisioned and Accomplished in Manitoba (DREAM) Theme, MB, Canada.|e Department of Pharmacology and Therapeutics, University of Manitoba, MB, Canada.|f Division of Clinical Pharmacology, Department of Internal Medicine, University of Manitoba, MB, Canada.
authors: Geert W
authors: GW
authors: T' Jong
authors: a Pediatrics and Child Health, University of Manitoba, MB, Canada.|b The Manitoba Institute of Child Health: Diabetes Research Envisioned and Accomplished in Manitoba (DREAM) Theme, MB, Canada.
authors: Jonathon
authors: J
authors: McGavock
authors: d Winnipeg Regional Health Authority, MB, Canada.
authors: Marni
authors: M
authors: Robert
authors: b The Manitoba Institute of Child Health: Diabetes Research Envisioned and Accomplished in Manitoba (DREAM) Theme, MB, Canada.|g Health, Leisure and Human Performance Research Institute, Kinesiology and Recreational Management, University of Manitoba, MB, Canada.|h Institute of Cardiovascular Sciences, St. Boniface Hospital, MB, Canada.
authors: Todd
authors: T
authors: Duhamel
authors: b The Manitoba Institute of Child Health: Diabetes Research Envisioned and Accomplished in Manitoba (DREAM) Theme, MB, Canada.|e Department of Pharmacology and Therapeutics, University of Manitoba, MB, Canada.
authors: Vernon W
authors: VW
authors: Dolinsky
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D019587:Dietary Supplements; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007333:Insulin Resistance; D008297:Male; D065626:Non-alcoholic Fatty Liver Disease / Q000188:drug therapy*; D050177:Overweight / Q000188:drug therapy*; D063766:Pediatric Obesity / Q000188:drug therapy*; D000077185:Resveratrol; D013267:Stilbenes / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*
chemical_list: D013267:Stilbenes; D000077185:Resveratrol
keywords: adolescents; diabète de type 2; non-alcoholic fatty liver disease; obesity; obésité; steatosis; stéatose; stéatose hépatique non alcoolique; type 2 diabetes