Metabolic Effect of Metformin in Obese Insulin Resistant Adolescents With Normal Glucose Tolerance

NCT00667498 | Completed Phase 4

• 1 other identifier: 0311026134
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Pediatric Obesity; Insulin Resistance; Hyperinsulinemia

Keywords

Pediatric Obesity; Insulin Resistance; Hyperinsulinemia; Metformin; Glucose Tolerance; Microalbuminuria; Adolescents; Visceral Fat

Outcome Measures

Primary Outcomes (1)

• Assessment of insulin sensitivity: Whole Body Insulin Sensitivity Index (WBISI), Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), and Euglycemic hyperinsulinemic clamp

  Baseline (month 0), post 3-month intervention (month 4), and post 6-month extension (month 10).

Secondary Outcomes (19)

• Body mass index (BMI)

  Baseline (month 0), post 3-month intervention (month 4), and post 6-month extension (month 10).

• Waist to hip circumference ratio

  Baseline (month 0), post 3-month intervention (month 4), and post 6-month extension (month 10).

• Muscle lipid content

  Baseline (month 0), post 3-month intervention (month 4), and post 6-month extension (month 10).

• Total body fat

  Baseline (month 0), post 3-month intervention (month 4), and post 6-month extension (month 10).

• Abdominal fat mass

  Baseline (month 0), post 3-month intervention (month 4), and post 6-month extension (month 10).

Study Arms (2)

1

EXPERIMENTAL

Drug: Metformin

2

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Metformin DRUG

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.

Also known as: Glucophage, Glucophage XR, Glumetza, Fortamet, Riomet

1

Placebo DRUG

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.

2

Eligibility Criteria

• Age: 13 Years - 17 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• Yale University: lead
• National Institutes of Health (NIH): collaborator

Study Sites (1)

Yale Center for Clinical Investigation (YCCI)

New Haven, Connecticut, 06511, United States

Location

Related Publications (1)

• 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. doi: 10.1111/j.1399-5448.2008.00434.x. Epub 2008 Aug 27.

  PMID: 18761646 RESULT

MeSH Terms

Conditions

Pediatric Obesity; Insulin Resistance; Hyperinsulinism

Interventions

Metformin

Condition Hierarchy (Ancestors)

Obesity; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Glucose Metabolism Disorders; Metabolic Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• Tania S Burgert, MD

  Yale University Medical School

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: April 24, 2008
• First Posted: April 28, 2008
• Study Start: March 1, 2004
• Primary Completion: December 1, 2007
• Study Completion: December 1, 2007
• Last Updated: February 18, 2009

Record last verified: 2009-02

Locations

US (1)