Metformin in Obese Children and Adolescents - Full Text View

Purpose

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

Condition	Intervention	Phase
Obesity Insulin Resistance	Drug: Metformin Behavioral: Lifestyle intervention	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator) Primary Purpose: Treatment
Official Title:	An Efficacy, Safety and Pharmacokinetic Study on the Short-term and Long-term Use of Metformin in Obese Children and Adolescents

Resource links provided by NLM:

MedlinePlus related topics: Diabetes Medicines Obesity

Drug Information available for: Metformin Metformin hydrochloride

U.S. FDA Resources

Further study details as provided by St. Antonius Hospital:

Primary Outcome Measures:

Change in BMI from baseline [ Time Frame: 18 months and 36 months ] [ Designated as safety issue: No ]
Change in BMI after part 1 (double blind) and part 2 ( follow-up)
Change in Insulin resistance from baseline [ Time Frame: 3; 6; 9; 12; 15; 18; 24; 30 and 36 months ] [ Designated as safety issue: No ]
calculated by the HOMA-IR.

Secondary Outcome Measures:

Renal and hepatic function [ Time Frame: 3; 6; 9; 12; 15; 18; 24; 30 and 36 months ] [ Designated as safety issue: Yes ]
Kreatinin and alat
Tolerability [ Time Frame: 3; 6; 9; 12; 15; 18; 24; 30 and 36 months ] [ Designated as safety issue: No ]
The amount of reported adverse effects, in relation to the achieved dose level.
PK-parameters: clearance (ml/min) [ Time Frame: 9 months ] [ Designated as safety issue: No ]
Clearance where applicable expressed per body weight, age category, Tanner Stage and gender, clearance will be determined with a two-compartment pharmacokinetic model using non linear mixed effect modelling.
Body fat percentage [ Time Frame: 0, 9, 18 and 36 months ] [ Designated as safety issue: No ]
Physical fitness [ Time Frame: 0, 9, 18 and 36 months ] [ Designated as safety issue: No ]
Quality of life [ Time Frame: 0, 9, 18 and 36 months ] [ Designated as safety issue: No ]
Long term efficacy [ Time Frame: 36 months ] [ Designated as safety issue: No ]
Based on BMI and HOMA-IR values
Long-term safety [ Time Frame: 36 months ] [ Designated as safety issue: Yes ]
Renal and hepatic function after 36 months of metformin use
Long-term tolerability [ Time Frame: 36 months ] [ Designated as safety issue: No ]
The amount of adverse effects after 36 months
Microvascular complications [ Time Frame: 36 months ] [ Designated as safety issue: No ]
Measured as micro-albuminuria
Macrovascular complications [ Time Frame: 36 monthts ] [ Designated as safety issue: No ]
Measured with Pulse Wave Velocity and Augmentation Index.
Development of T2DM [ Time Frame: 36 months ] [ Designated as safety issue: No ]
PK-parameters: volume of distribution (liters) [ Time Frame: 9 months ] [ Designated as safety issue: No ]
Volume of distribution, where applicable expressed per body weight, age category, Tanner Stage and gender, volume of distribution will be determined with a two-compartment pharmacokinetic model using non linear mixed effect modelling.

Estimated Enrollment:	144
Study Start Date:	August 2011
Estimated Study Completion Date:	January 2016
Estimated Primary Completion Date:	July 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Metformin Metformin with lifestyle intervention during 18 months	Drug: Metformin 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. Other Name: Glucophage Behavioral: Lifestyle intervention Lifestyle intervention: 18 months physical therapy and dietary advice
Placebo Comparator: Placebo Placebo and lifestyle intervention during 18 months	Behavioral: Lifestyle intervention Lifestyle intervention: 18 months physical therapy and dietary advice

Detailed 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.

Eligibility

Ages Eligible for Study:	10 Years to 16 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01487993

Contacts

Contact: Marloes P van der Aa, MD	+31306093775	m.van.der.aa@antoniusziekenhuis.nl
Contact: Marja MJ van der Vorst, MD, PhD	+31306096325	m.van.der.vorst@antoniusziekenhuis.nl

Locations

Netherlands
St. Antonius Hospital	Recruiting
Nieuwegein, Netherlands, 3430EM
Contact: Marloes P van der Aa, MD +31306093775 m.van.der.aa@antoniusziekenhuis.nl
Contact: Marja MJ van der Vorst, MD, PhD +31306096325 m.van.der.vorst@antoniusziekenhuis.nl
Principal Investigator: Marja MJ van der Vorst, MD, PhD
Sub-Investigator: Marloes P van der Aa, MD

Sponsors and Collaborators

St. Antonius Hospital

HagaZiekenhuis

Jeroen Bosch Ziekenhuis

Investigators

Principal Investigator:

Marja MJ van der Vorst, MD, PhD

St. Antonius Hospital

More Information

No publications provided

Responsible Party:	Van der Vorst, Mrs. M.M.J. van der Vorst, paediatrician-clinical pharmacologist, St. Antonius Hospital
ClinicalTrials.gov Identifier:	NCT01487993 History of Changes
Other Study ID Numbers:	Metformin 2011-3, 2010-023980-17
Study First Received:	October 20, 2011
Last Updated:	December 6, 2011
Health Authority:	Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by St. Antonius Hospital:

Obesity
Children
Adolescents
Metformin
Insulin resistance

Additional relevant MeSH terms:

Insulin Resistance
Obesity
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Overnutrition
Nutrition Disorders

Overweight
Body Weight
Signs and Symptoms
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on June 18, 2013

Metformin in Obese Children and Adolescents (MetVoorMin)