This trial will test the hypothesis that among obese adolescents, treatment with extended-release metformin (Glucophage® XR), coupled with a lifestyle intervention, will result in decreased obesity (as measured by body mass index [BMI]) as compared to subjects who receive treatment with placebo and the same lifestyle intervention.

Condition	Intervention	Phase
Obesity	Drug: Metformin	Phase III

Further Study Details: 

Primary Outcomes: Change in BMI; Body mass index (BMI)
Secondary Outcomes: Change in insulin sensitivity; Fasting insulin concentrations; Characterization of insulin dynamics and insulin sensitivity; Characterization of fat distribution and fatty infiltration of the liver; Use of CT to characterize abdominal fat distribution; Use of CT and ALT levels to assess fatty infiltration of the liver; Characterization of body composition; Characterization of dietary amino acids; Characterization of the insulin/glucagon ratio; Characterization of the impact of gender on response to metformin XR; Characterization of the impact of race/ethnicity on response to metformin XR; Characterization of health-related quality of life
Expected Total Enrollment:  22

Ages Eligible for Study:  13 Years   -   17 Years,  Genders Eligible for Study:  Both

Accepts Healthy Volunteers

Criteria

Inclusion Criteria:

• Subjects must be between the ages of 13.00 and 17.99 at week 0 (Baseline)
• Subjects must have a BMI > 95th percentile for age and gender using the CDC data, and must weigh less than 300 pounds (< 136 kilograms) at week 0 (Baseline)
• Completion of informed consent/assent process

Exclusion Criteria:

Subjects will be excluded from the study for any of the following:

• Known diabetes as defined by the American Diabetes Association criteria.
• Prior drug therapy to treat diabetes or insulin insensitivity
• Has ever used a medication to aid in weight loss
• Subject is currently taking the following medications at the time of the Screening visit: cimetidine, amiloride, digoxin, furosemide, morphine, nifedipine, procainamide, ranitidine, triamterene, trimethoprim, vancomycin and quinidine, as these medications may increase metformin levels.
• Recent glucocorticoid therapy
• History of any syndrome or medical disorder associated with significant obesity
• Recent history of involvement in a formal weight loss program
• Alcohol use
• Elevated creatinine (> 1.2 mg/dl)
• Untreated disorders of thyroid function
• Elevated liver enzymes (Alanine Aminotransferase [ALT] or Aspartate Aminotransferase [AST]) > 80 (approximately 2 times upper limit of normal). An AST or ALT of > 2 times upper limit of normal was chosen based on data which show that approximately 5% of obese adolescents have liver enzymes greater than 2 times the upper limit of normal in the clinical setting.
• Mobility impairment that prevents full participation in recommended physical activity
• Other serious medical condition that the Principal Investigator or Lead Site Investigator determines may put the patient at undue risk if enrolled in the study
• Unable to comply with the protocol in the opinion of the Principal Investigator or the Lead Site Investigator
• Subjects with child-bearing potential who are unwilling to remain abstinent or use an effective method of birth control. Females who have had at least one menstrual cycle must either be abstinent or must consistently be using an effective method of birth control (e.g., intrauterine contraceptive device, oral contraceptive or medroxyprogesterone acetate or barrier method [diaphragm or condom] plus contraceptive jelly, cream, or foam) during the study. This will be documented at each visit. Additionally, all females who have begun menstruating must have a negative result on the urine pregnancy test administered at every visit in order to remain on study drug and undergo radiologic procedures.
• Previous pregnancy

Please refer to this study by ClinicalTrials.gov identifier  NCT00120146

Carol Sweeney, BS, BSN      617-355-2323    carol.sweeney@childrens.harvard.edu

Massachusetts
      Children''''s Hospital, Boston, Boston,  Massachusetts,  02115,  United States; Recruiting

Study chairs or principal investigators

Carine Lenders, MD,  Principal Investigator,  Children''''s Hospital Boston   

Study ID Numbers:  02-10-132
Record last reviewed:  September 2004
Last Updated:  July 18, 2005
Record first received:  July 15, 2005
ClinicalTrials.gov Identifier:  NCT00120146
Health Authority: United States: Institutional Review Board
ClinicalTrials.gov processed this record on 2005-07-26