Activity and Metformin Intervention in Obese Adolescents

Study Overview
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Brief Summary
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The purpose of this study is to assess the sustainability of a two-year intervention aimed at improving body mass index (BMI) and metabolic and vascular health in obese youth. The study will compare lifestyle changes with diet and exercise alone with changes in lifestyle in combination with metformin medication. An initial intensive exercise program will also be compared with a standard exercise program. Hypothesis: Metformin therapy in combination with intensive lifestyle intervention in obese children and adolescents will be associated with reduced rate of weight gain, improved BMI, body composition, physical activity, physical fitness, insulin sensitivity, blood lipid profiles, adipocytokines and vascular function.

Detailed Description
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This study will assess the sustainability of a two-year intervention and the degree of improvement in body mass index (BMI) and reduction in risk factors for type 2 diabetes and diabetes related cardiovascular disease, as well as evaluating the additive effect of metformin (as GlumetzaTM 500 mg Extended Release Tablets) and comparing an initial intensive exercise program with a standard exercise program. The study will recruit obese youth who are at risk for type 2 diabetes and cardiovascular disease.

Official Title
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Reduction of Adolescent Risk Factors for Type 2 Diabetes and Cardiovascular Disease

Conditions
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Obesity, Type 2 Diabetes

Intervention / Treatment
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* Drug: Metformin and standard exercise
* Drug: Metformin Intensive exercise
* Behavioral: Placebo Standard exercise
* Behavioral: Intensive exercise


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Obese adolescents defined as BMI greater than the 95th percentile for age and gender Metformin naive subjects Exclusion Criteria: Elevated fasting plasma glucose ≥ 6.0 mmol/L 2 hour plasma glucose ≥ 11.1 mmol/L after a standard glucose load A1C > 6.0% Medication other than over the counter drugs, oral contraceptive pill or thyroid hormone replacement Smoking Pregnancy Renal insufficiency (serum creatinine > the upper limit of normal) Hepatic dysfunction (> 1.5 times the upper limit of normal for AST and ALT) Latex Allergy Hypersensitivity to metformin or its ingredients Breast feeding Subjects with a history of lactic acidosis Abnormal creatinine clearance HIV, HBV, and HCV infections Drug and alcohol abuse Severe mental disorders Subjects who are planning radiologic exams involving in i.v. injection of iodinated contract materials Participation in another clinical trial Significant history or presence of cardiovascular, pulmonary, gastrointestinal, immunologic, endocrine, neurologic disorders Malignant diseases Previous exposure to any pharmaceutical antidiabetic agent

Ages Eligible for Study
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Minimum Age: 10 Years
Maximum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Metformin, Standard exercise<br>Lifestyle intervention with metformin and standard exercise program. | Drug: Metformin and standard exercise<br>* Metformin 1500 mg daily for 2 years<br>* Other names: GlumetzaTM 500 mg Extended Release;|
| Placebo Comparator: Placebo, Standard exercise<br>Lifestyle intervention with placebo and standard exercise program | Behavioral: Placebo Standard exercise<br>* Standard exercise<br>|
| Active Comparator: Metformin, Intensive exercise<br>Lifestyle intervention with metformin and intensive exercise | Drug: Metformin Intensive exercise<br>* Metformin 1500 mg daily for 2 years<br>* Other names: GlumetzaTM 500 mg Extended Release;|
| Placebo Comparator: Placebo, Intensive exercise<br>Lifestyle intervention with placebo and intensive exercise program. | Behavioral: Intensive exercise<br>* Placebo Intensive exercise<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction in BMI |  | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement in physical activity |  | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Obesity, Metformin, Physical activity, Cardiovascular health