Metformin in Obese Children and Adolescents (MetVoorMin)

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2013 by St. Antonius Hospital
Sponsor:
Collaborator:
Jeroen Bosch Ziekenhuis
Information provided by (Responsible Party):
Van der Vorst, St. Antonius Hospital
ClinicalTrials.gov Identifier:
NCT01487993
First received: October 20, 2011
Last updated: August 21, 2013
Last verified: August 2013
  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:


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 Homeostasis Model Assessment for Insulin Resistance (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 ]
    creatinine 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.

  • Pharmacokinetics (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: February 2017
Estimated Primary Completion Date: August 2015 (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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Contacts
Contact: Marieke MAJ Elst, MD +31306093775 m.elst@antoniusziekenhuis.nl
Contact: Marja MJ van der Vorst, MD, PhD +31306096325 m.van.der.vorst@antoniusziekenhuis.nl

Locations
Netherlands
Jeroen Bosch Hospital Recruiting
's Hertogenbosch, Netherlands
Contact: Marieke AJ Elst, MD    +31 30 609 3775    m.elst@antoniusziekenhuis.nl   
Contact: Edgar GAH van Mil, MD, PhD    +31 73 553 2304    e.g.vanmil@jbz.nl   
Principal Investigator: Edgar GAH van Mil, MD, PhD         
Sub-Investigator: Marieke AJ Elst, MD         
St. Antonius Hospital Recruiting
Nieuwegein, Netherlands, 3430EM
Contact: Marieke AJ Elst, MD    +31306093775    m.elst@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         
Sub-Investigator: Marieke AJ Elst, MD         
Sponsors and Collaborators
St. Antonius Hospital
Jeroen Bosch Ziekenhuis
Investigators
Principal Investigator: Marja MJ van der Vorst, MD, PhD St. Antonius Hospital
  More Information

No publications provided by St. Antonius Hospital

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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 2011-6, 2010-023980-17
Study First Received: October 20, 2011
Last Updated: August 21, 2013
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 August 20, 2014