Metabolic Effect of Metformin in Obese Insulin Resistant Adolescents With Normal Glucose Tolerance
This study has been completed.
Sponsor:
Yale University
Collaborator:
Information provided by:
Yale University
ClinicalTrials.gov Identifier:
NCT00667498
First received: April 24, 2008
Last updated: February 16, 2009
Last verified: February 2009
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Purpose
The primary objective of this randomized, parallel group, double-blind, placebo-controlled study is to determine whether treatment with metformin enhances insulin sensitivity in a group of ethnically diverse obese insulin-resistant adolescents with normal glucose tolerance.
| Condition | Intervention | Phase |
|---|---|---|
|
Pediatric Obesity Insulin Resistance Hyperinsulinemia |
Drug: Metformin Drug: Placebo |
Phase 4 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator) Primary Purpose: Treatment |
| Official Title: | Metabolic Effect of Metformin in Obese Insulin Resistant Adolescents With Normal Glucose Tolerance |
Resource links provided by NLM:
Further study details as provided by Yale University:
Primary Outcome Measures:
- Assessment of insulin sensitivity: Whole Body Insulin Sensitivity Index (WBISI), Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), and Euglycemic hyperinsulinemic clamp [ Time Frame: Baseline (month 0), post 3-month intervention (month 4), and post 6-month extension (month 10). ] [ Designated as safety issue: Yes ]
Secondary Outcome Measures:
- Body mass index (BMI) [ Time Frame: Baseline (month 0), post 3-month intervention (month 4), and post 6-month extension (month 10). ] [ Designated as safety issue: No ]
- Waist to hip circumference ratio [ Time Frame: Baseline (month 0), post 3-month intervention (month 4), and post 6-month extension (month 10). ] [ Designated as safety issue: No ]
- Muscle lipid content [ Time Frame: Baseline (month 0), post 3-month intervention (month 4), and post 6-month extension (month 10). ] [ Designated as safety issue: No ]
- Total body fat [ Time Frame: Baseline (month 0), post 3-month intervention (month 4), and post 6-month extension (month 10). ] [ Designated as safety issue: No ]
- Abdominal fat mass [ Time Frame: Baseline (month 0), post 3-month intervention (month 4), and post 6-month extension (month 10). ] [ Designated as safety issue: No ]
- Hepatic fat fraction [ Time Frame: Baseline (month 0), post 3-month intervention (month 4), and post 6-month extension (month 10). ] [ Designated as safety issue: No ]
- Hepatic iron concentration [ Time Frame: Baseline (month 0), post 3-month intervention (month 4), and post 6-month extension (month 10). ] [ Designated as safety issue: No ]
- Plasma ghrelin levels [ Time Frame: Baseline (month 0), post 3-month intervention (month 4), and post 6-month extension (month 10). ] [ Designated as safety issue: No ]
- Adiponectin levels [ Time Frame: Baseline (month 0), post 3-month intervention (month 4), and post 6-month extension (month 10). ] [ Designated as safety issue: No ]
- Leptin levels [ Time Frame: Baseline (month 0), post 3-month intervention (month 4), and post 6-month extension (month 10). ] [ Designated as safety issue: No ]
- Blood pressure [ Time Frame: Baseline (month 0), post 3-month intervention (month 4), and post 6-month extension (month 10). ] [ Designated as safety issue: No ]
- Lipid profile [ Time Frame: Baseline (month 0), post 3-month intervention (month 4), and post 6-month extension (month 10). ] [ Designated as safety issue: No ]
- Microalbuminuria [ Time Frame: Baseline (month 0), post 3-month intervention (month 4), and post 6-month extension (month 10). ] [ Designated as safety issue: No ]
- Inflammatory markers (Plasminogen activator inhibitor-1 (PAI-1), C-reactive protein (CRP), homocysteine, tumor necrosis factor (TNF)-α, Interleukin (IL)-6) [ Time Frame: Baseline (month 0), post 3-month intervention (month 4), and post 6-month extension (month 10). ] [ Designated as safety issue: No ]
- Self-paced step test (Heart rate recovery after exercise) [ Time Frame: Baseline (month 0), post 3-month intervention (month 4), and post 6-month extension (month 10). ] [ Designated as safety issue: No ]
- Peripheral Arterial Tonometry (PAT) [ Time Frame: Baseline (month 0), post 3-month intervention (month 4), and post 6-month extension (month 10). ] [ Designated as safety issue: No ]
- Females only: Markers of polycystic ovarian syndrome (PCOS) - Adrenal androgens (17 Hydroxyprogesterone, Dehydroepiandrosterone), sex hormone binding globulin (SHBG), free testosterone, LH/FSH ratio [ Time Frame: Baseline (month 0), post 3-month intervention (month 4), and post 6-month extension (month 10). ] [ Designated as safety issue: No ]
- Females only: Menstrual pattern [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
- Ethnic stratification (Hispanic, African American or Caucasian) [ Time Frame: Baseline (month 0) ] [ Designated as safety issue: No ]
| Enrollment: | 28 |
| Study Start Date: | March 2004 |
| Study Completion Date: | December 2007 |
| Primary Completion Date: | December 2007 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
| Experimental: 1 |
Drug: Metformin
The subject will receive either metformin or placebo drug, given as 500mg tablets (or corresponding placebos) necessary to increase the dose incrementally over a three week period. The time it takes to incrementally increase the dose to the desired dose of 500mg in am and 1000mg in pm will count as intervention time. Both the metformin and placebo group will also be given a multivitamin with vitamin B12 to avoid potential anemia. Other Name: Glucophage, Glucophage XR, Glumetza, Fortamet, Riomet
|
| Placebo Comparator: 2 |
Drug: Placebo
The subject will receive either metformin or placebo drug, given as 500mg tablets (or corresponding placebos) necessary to increase the dose incrementally over a three week period. The time it takes to incrementally increase the dose to the desired dose of 500mg in am and 1000mg in pm will count as intervention time. Both the metformin and placebo group will also be given a multivitamin with vitamin B12 to avoid potential anemia. Other Name: Placebo
|
Show Detailed Description Eligibility| Ages Eligible for Study: | 13 Years to 17 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | Yes |
Criteria
Inclusion Criteria:
- Attending weight management clinic at Yale New Haven Hospital
- Good general health, taking no other medication on a chronic basis
- Age 13 to 17 yrs in puberty (girls: breast Tanner stage II to IV, and boys: testes size > 6 ml)
- The presence of insulin resistance, defined by fasting insulin levels greater than 30 µU/ml, and HOMA insulin resistance index > 6
- Normal glucose tolerance based on a 2-hr plasma glucose (<140 mg/dl) after the OGTT.
- All female subjects must have a negative urine pregnancy test during the study visits and must use an effective method of contraception if they are sexually active. Without their parent(s) present, all potential female subjects will be asked about their sexual activity and the specific form of contraception they are using.
Exclusion Criteria:
- Baseline creatinine > 1.0 mg/dl
- Hepatic disease with elevated liver function test (ALT or AST) ≥ 2 X the upper limits of normal
- Pregnancy
- Presence of other endocrinopathies; except treated hypothyroidism on stable replacement doses of thyroid hormone
- Presence of cardiac, pulmonary or other significant chronic illness
- Adolescents with psychiatric disorder, claustrophobia or with substance abuse
- Recent use (within six months) of anorexic agents
- Presence of anemia (hematocrit < 35)
- Mixed ethnic background (defined as two parents of different ethnicity)
- Adolescents with metal implants (i.e. cardiac pace maker, metal prostheses, bullet remnants)
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00667498
Locations
| United States, Connecticut | |
| Yale Center for Clinical Investigation (YCCI) | |
| New Haven, Connecticut, United States, 06511 | |
Sponsors and Collaborators
Yale University
Investigators
| Principal Investigator: | Tania S Burgert, MD | Yale University Medical School |
More Information
Publications:
| Responsible Party: | Tania S. Burgert, M.D., Yale University |
| ClinicalTrials.gov Identifier: | NCT00667498 History of Changes |
| Other Study ID Numbers: | 0311026134 |
| Study First Received: | April 24, 2008 |
| Last Updated: | February 16, 2009 |
| Health Authority: | United States: Federal Government United States: Institutional Review Board |
Keywords provided by Yale University:
|
Pediatric Obesity Insulin Resistance Hyperinsulinemia Metformin |
Glucose Tolerance Microalbuminuria Adolescents Visceral Fat |
Additional relevant MeSH terms:
|
Hyperinsulinism Insulin Resistance Obesity Glucose Metabolism Disorders Metabolic Diseases Overnutrition Nutrition Disorders Overweight |
Body Weight Signs and Symptoms Insulin Metformin Hypoglycemic Agents Physiological Effects of Drugs Pharmacologic Actions |
ClinicalTrials.gov processed this record on May 19, 2013