Metabolic Effect of Metformin in Obese Insulin Resistant Adolescents With Normal Glucose Tolerance - Full Text View

Sponsor:	Yale University
Collaborator:	National Institutes of Health (NIH)
Information provided by:	Yale University
ClinicalTrials.gov Identifier:	NCT00667498

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 IV

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:

MedlinePlus related topics: Diabetes Medicines Obesity

Drug Information available for: Insulin Insulin beef Dextrose Metformin Metformin hydrochloride

U.S. FDA Resources

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

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

National Institutes of Health (NIH)

Investigators

Principal Investigator:

Tania S Burgert, MD

Yale University Medical School

More Information

Publications:

Burgert TS, Duran EJ, Goldberg-Gell R, Dziura J, Yeckel CW, Katz S, Tamborlane WV, Caprio S. Short-term metabolic and cardiovascular effects of metformin in markedly obese adolescents with normal glucose tolerance. Pediatr Diabetes. 2008 Dec;9(6):567-76. Epub 2008 Aug 27.

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 February 13, 2012