Metformin to Treat Obesity in Children With Insulin Resistance
This study will examine the safety and effectiveness of the medicine metformin to help overweight children control their food intake, weight, insulin, cholesterol, and triglyceride (blood fat) levels. Obesity and high insulin levels can lead to high blood pressure, diabetes, high cholesterol and triglyceride levels and heart disease. Metformin-approved by the Food and Drug Administration to treat adults with type 2 diabetes mellitus-helps lower insulin levels and may control weight gain in adults.
Overweight children 6 to 11 years old who are in general good health may be eligible for this study. Children will be studied at the National Institutes of Health in Bethesda, Maryland. Candidates will have a medical history and physical examination and fasting blood test, and will provide a 7-day record of their food intake as part of the screening process. Those enrolled will be randomly assigned to receive either metformin or placebo (a look-alike tablet with no active medicine) twice a day for a six month period. After the 6 month study period, all children will be offered the opportunity to take metformin for another 6 months.
Participants will be hospitalized for 2-3 days for the following procedures: history and physical examination; fasting blood test; several urine collections; X-ray studies to determine bone age and amount of body fat and muscle; magnetic resonance imaging (MRI) scan to measure body fat; "hyperglycemic clamp study" to evaluate insulin resistance; food intake testing; nutrition consultation; resting metabolic rate; and a "doubly labeled water" test.
For the hyperglycemic clamp study, a catheter (thin flexible tube) is inserted into a vein in each arm. A sugar solution is given through one tube and blood samples are drawn every 5 minutes through the other to measure insulin. For the food intake testing, the child is asked about his or her hunger level, then given various foods he or she may choose to eat, then questioned again at various intervals both during and after finishing eating about his or her hunger level. The doubly labeled water study involves drinking "heavy water" (water which is enriched to have special kinds of hydrogen and oxygen). Urine specimens are collected 2, 3 and 4 hours after drinking the water. The child also drinks a special milk shake called a Scandishake and repeats the calorie intake and hunger study. (Two food intake studies are done on separate days.) One week after the heavy water test, additional urine samples are collected one week later.
After completing the tests, the child will begin treatment with metformin or placebo, plus a daily vitamin tablet. Participants will be followed once a month with a brief history and physical examination, including a blood test. After 6 months, all of the tests described above will be repeated. All children who complete the second round of tests-both those who took metformin and those who took placebo-will be offered metformin for an additional 6 months and will be seen once a month for follow-up evaluations. Parents will not be told which children received metformin and which received placebo until all children in the study complete the first 6 months of the trial.
The prevalence of overweight and obesity in children and adolescents in the United States has doubled during the past 20 years. Obesity is closely linked with development of insulin resistance and other mediators of unfavorable cardiovascular risk, such as hypertension and dyslipidemia. These obesity-related risk factors often first appear during childhood. Since obese children tend to become obese adults, such children are at increased risk for persistence of these abnormalities into adulthood and for the early occurrence of obesity-related morbidity and mortality. Obesity-related insulin resistance is also largely responsible for the recently documented rise in the incidence of Type 2 diabetes in youth. To date, there is no FDA-approved pharmacotherapy for children with obesity and insulin resistance. Metformin is a medication approved for use in adults with Type 2 diabetes that is unique in that it promotes weight loss and improves features of the insulin resistance syndrome. Preliminary studies suggest that metformin may promote weight loss in obese non-diabetic children. However, the mechanism of metformin-induced weight loss has not been elucidated. We propose to evaluate the safety, tolerability, efficacy and mechanism of metformin-induced weight loss in obese, hyperinsulinemic children aged 6-12.99 years. We will conduct a six-month randomized, double blind placebo-controlled trial of metformin. All study participants will receive nutritional consultation and advice on appropriate diet. We will study the effects of metformin on weight, food intake, energy expenditure, insulin sensitivity, and lipids. At the end of the six-month placebo-controlled trial, all subjects will be offered metformin in an open label phase for an additional six months.
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Metformin HCL, Placebo
National Institutes of Health Clinical Center, 9000 Rockville Pike
Active, not recruiting
National Institutes of Health Clinical Center (CC)
Results (where available)
- Source: http://clinicaltrials.gov/show/NCT00005669
- Information obtained from ClinicalTrials.gov on July 15, 2010
Acanthosis Nigricans is skin disease that associated with hyperinsulinemia. Clinical is velvety hyperpigmented plaques on neck, axilla, groin. If hyperinsulinemia is improved by treated wi...
This trial is conducted in Europe, Oceania, Africa, Asia and South America. This trial is designed to show the effect of treatment with liraglutide when adding to existing metformin therap...
The purpose of this study was to study the effect of different combinations of fenofibrate and metformin on the cluster of metabolic syndrome (MetS) biochemical abnormalities, and to deter...
Study to Evaluate 24 Hour Blood Sugar Control in Subjects That Are Taking Saxagliptin 5 mg Added Onto Metformin XR 1500 XR mg Compared to Subjects Taking Metformin XR 1500 mg Uptitrated to Metformin XR 2000 mg
The purpose of this study is to compare reduction in A1C for subjects taking Saxagliptin and Metformin XR versus uptitrated Metformin XR.
A more recent prospective nonrandomized placebo-controlled double-blind clinical study demonstrated that metformin exerts a slight but significant deleterious effect on serum homocysteine ...
Antidiabetic drug metformin that improves insulin sensitivity and used in the treatment of nonalcoholic fatty liver disease (NAFLD), may affect the bone health. Our study was designed to investigate a...
To compare weight loss in the first 6 weeks postpartum among women with gestational diabetes (GDM) treated with metformin or placebo, a promising therapy to reduce later risk of progression to DM.
BACKGROUND Evidence indicates that insulin resistance results in poor sustained viral response (SVR) in patients with chronic hepatitis C (CHC). Metformin is an oral hypoglycemic agent which improves ...
The Effect of Lifestyle Intervention and Metformin on Preventing or Delaying Diabetes Among Women With and Without Gestational Diabetes: The Diabetes Prevention Program Outcomes Study 10-Year Follow-Up.
Context: Gestational diabetes (GDM) confers a high risk of type 2 diabetes. In the Diabetes Prevention Program (DPP), intensive lifestyle (ILS) and metformin prevented or delayed diabetes in women wit...
To compare efficacy and safety of dulaglutide, a once weekly glucagon-like peptide1 receptor agonist, to placebo and exenatide in type 2 diabetes patients. Primary objective was superiority of dulaglu...
Medical and Biotech [MESH] Definitions
A biguanide hypoglycemic agent used in the treatment of non-insulin-dependent diabetes mellitus not responding to dietary modification. Metformin improves glycemic control by improving insulin sensitivity and decreasing intestinal absorption of glucose. (From Martindale, The Extra Pharmacopoeia, 30th ed, p289)
A form of nontransient HYPOGLYCEMIA, unique to infancy, due to autosomal recessive mutations of the sulfonylurea receptor gene on CHROMOSOME 11. Defects in the sulfonylurea receptors (ATP-BINDING CASSETTE TRANSPORTERS) on the PANCREATIC BETA CELLS prevent negative feedback of GLUCOSE-regulated INSULIN release thus resulting in HYPERINSULINEMIA. Clinical phenotype includes SEIZURES; COMA; and often large BIRTH WEIGHT for GESTATIONAL AGE.
Misunderstanding among individuals, frequently research subjects, of scientific methods such as randomization and placebo controls.
A biguanide hypoglycemic agent with actions and uses similar to those of METFORMIN. Although it is generally considered to be associated with an unacceptably high incidence of lactic acidosis, often fatal, it is still available in some countries. (From Martindale, The Extra Pharmacopoeia, 30th ed, p290)
An effect usually, but not necessarily, beneficial that is attributable to an expectation that the regimen will have an effect, i.e., the effect is due to the power of suggestion.