Overview

This trial is active, not recruiting.

Conditions obesity, insulin resistance
Treatments metformin, lifestyle intervention
Phase phase 3
Sponsor St. Antonius Hospital
Collaborator Jeroen Bosch Ziekenhuis
Start date August 2011
End date August 2015
Trial size 144 participants
Trial identifier NCT01487993, 2010-023980-17, Metformin 2011-6

Summary

The purpose of this study is to determine whether metformin is effective in reducing BMI and insulin resistance in obese children and adolescents.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator)
Primary purpose treatment
Arm
(Active Comparator)
Metformin with lifestyle intervention during 18 months
metformin Glucophage
Oral administration, 500 mg daily at week 1. Every week metformin dosage increases with 500 mg, to a maximum dose of 1000 mg bid. This maximum dose will be administered till the end of the study.
lifestyle intervention
Lifestyle intervention: 18 months physical therapy and dietary advice
(Placebo Comparator)
Placebo and lifestyle intervention during 18 months
lifestyle intervention
Lifestyle intervention: 18 months physical therapy and dietary advice

Primary Outcomes

Measure
Change in BMI from baseline
time frame: 18 months and 36 months
Change in Insulin resistance from baseline
time frame: 3; 6; 9; 12; 15; 18; 24; 30 and 36 months

Secondary Outcomes

Measure
Renal and hepatic function
time frame: 3; 6; 9; 12; 15; 18; 24; 30 and 36 months
Tolerability
time frame: 3; 6; 9; 12; 15; 18; 24; 30 and 36 months
Pharmacokinetics (PK)-parameters: clearance (ml/min)
time frame: 9 months
Body fat percentage
time frame: 0, 9, 18 and 36 months
Physical fitness
time frame: 0, 9, 18 and 36 months
Quality of life
time frame: 0, 9, 18 and 36 months
Long term efficacy
time frame: 36 months
Long-term safety
time frame: 36 months
Long-term tolerability
time frame: 36 months
Microvascular complications
time frame: 36 months
Macrovascular complications
time frame: 36 monthts
Development of T2DM
time frame: 36 months
PK-parameters: volume of distribution (liters)
time frame: 9 months

Eligibility Criteria

Male or female participants from 10 years up to 16 years old.

Inclusion Criteria: - Age ≥ 10 and ≤ 16 years at study entry - Caucasian descent - Obesity defined as BMI-SDS > 2.3 - Insulin resistance defined as HOMA-IR ≥ 3.4. - An obtained informed consent from subjects and parents/caregivers. Exclusion Criteria: - Presence of T2DM (American Diabetes Association criteria) - Presence of endocrine disorders with steroid therapy - Suspicion of polycystic ovarium syndrome; - Height < -1.3 SD of target height; - Syndrome disorders with or without mental retardation; - Use of anti-hyperglycaemic drugs; - Pregnancy (pregnancy test will be performed, if applicable); - (History of) alcohol abuse; - Impaired renal and/or hepatic function (defined as GFR < 80 ml/min. GFR=40 x length (cm) / serumcreatinin (μmol/l and ALAT >150% of normal value for age); - Use of ritonavir; use of ACE inhibitors; - Insufficient knowledge of the Dutch language.

Additional Information

Official title An Efficacy, Safety and Pharmacokinetic Study on the Short-term and Long-term Use of Metformin in Obese Children and Adolescents
Principal investigator Marja MJ van der Vorst, MD, PhD
Description The prevalence of obesity in children and adolescents is increasing rapidly and is associated with significant medical and psychosocial consequences persisting into adulthood. Obesity may lead to metabolic complications, such as insulin resistance, which can progress via impaired fasted glucose and impaired glucose tolerance to type 2 diabetes mellitus (T2DM) and to the development of micro- and macro-vascular complications. Metformin, an oral anti-diabetic licensed for T2DM for adults and children from 10 years onwards, is already used off label in obese children and adolescents with insulin resistance, even though the specific effects of metformin in these obese children and adolescents have not been elucidated, particularly upon long-term use. The rationale for this study is based on the hypothesis that metformin may reduce body mass index (BMI), insulin resistance and percentage of body-fat in obese children and adolescents with insulin resistance. Further more it is anticipated that metformin may delay the progression to T2DM and thereby micro- and macro-vascular complications in obese children and adolescents with insulin resistance.
Trial information was received from ClinicalTrials.gov and was last updated in September 2015.
Information provided to ClinicalTrials.gov by St. Antonius Hospital.