Metformin in Obese Children and Adolescents

Obesity Clinical Trial

— MetVoorMin  

Official title:

An Efficacy, Safety and Pharmacokinetic Study on the Short-term and Long-term Use of Metformin in Obese Children and Adolescents

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01487993
• Other study ID #: Metformin 2011-6
• Secondary ID: 2010-023980-17
• Status: Completed
• Phase: Phase 3
• First received: October 20, 2011
• Last updated: April 26, 2017
• Start date: August 2011
• Est. completion date: February 28, 2017

Study information

• Verified date: April 2017
• Source: St. Antonius Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 62
• Est. completion date: February 28, 2017
• Est. primary completion date: August 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 10 Years to 16 Years

Eligibility

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.

Related Conditions & MeSH terms

• Insulin Resistance
• Obesity

Intervention

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.

Behavioral:
• Lifestyle intervention
Lifestyle intervention: 18 months physical therapy and dietary advice

Locations

Country	Name	City	State
Netherlands	Jeroen Bosch Hospital	's Hertogenbosch
Netherlands	St. Antonius Hospital	Nieuwegein

Sponsors (2)

Lead Sponsor	Collaborator
St. Antonius Hospital	Jeroen Bosch Ziekenhuis

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in BMI from baseline	Change in BMI after part 1 (double blind) and part 2 ( follow-up)	18 months and 36 months
Primary	Change in Insulin resistance from baseline	calculated by the Homeostasis Model Assessment for Insulin Resistance (HOMA-IR).	3; 6; 9; 12; 15; 18; 24; 30 and 36 months
Secondary	Renal and hepatic function	creatinine and alat	3; 6; 9; 12; 15; 18; 24; 30 and 36 months
Secondary	Tolerability	The amount of reported adverse effects, in relation to the achieved dose level.	3; 6; 9; 12; 15; 18; 24; 30 and 36 months
Secondary	Pharmacokinetics (PK)-parameters: clearance (ml/min)	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.	9 months
Secondary	Body fat percentage		0, 9, 18 and 36 months
Secondary	Physical fitness		0, 9, 18 and 36 months
Secondary	Quality of life		0, 9, 18 and 36 months
Secondary	Long term efficacy	Based on BMI and HOMA-IR values	36 months
Secondary	Long-term safety	Renal and hepatic function after 36 months of metformin use	36 months
Secondary	Long-term tolerability	The amount of adverse effects after 36 months	36 months
Secondary	Microvascular complications	Measured as micro-albuminuria	36 months
Secondary	Macrovascular complications	Measured with Pulse Wave Velocity and Augmentation Index.	36 monthts
Secondary	Development of T2DM		36 months
Secondary	PK-parameters: volume of distribution (liters)	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.	9 months