Metformin in Obese Children and Adolescents

NCT01487993 | Completed Phase 3 DMC

• 2 other identifiers: Metformin 2011-62010-023980-17
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 2

Brief Summary

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

Conditions

Obesity; Insulin Resistance

Keywords

Obesity; Children; Adolescents; Metformin; Insulin resistance

Outcome Measures

Primary Outcomes (2)

• Change in BMI from baseline

  Change in BMI after part 1 (double blind) and part 2 ( follow-up)

  18 months and 36 months

• 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 Outcomes (13)

• Renal and hepatic function

  3; 6; 9; 12; 15; 18; 24; 30 and 36 months

• Tolerability

  3; 6; 9; 12; 15; 18; 24; 30 and 36 months

• Pharmacokinetics (PK)-parameters: clearance (ml/min)

  9 months

• Body fat percentage

  0, 9, 18 and 36 months

• Physical fitness

  0, 9, 18 and 36 months

Study Arms (2)

Metformin

ACTIVE COMPARATOR

Metformin with lifestyle intervention during 18 months

Drug: Metformin; Behavioral: Lifestyle intervention

Placebo

PLACEBO COMPARATOR

Placebo and lifestyle intervention during 18 months

Behavioral: Lifestyle intervention

Interventions

Metformin DRUG

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.

Also known as: Glucophage

Metformin

Lifestyle intervention BEHAVIORAL

Lifestyle intervention: 18 months physical therapy and dietary advice

Metformin; Placebo

Eligibility Criteria

• Age: 10 Years - 16 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• St. Antonius Hospital: lead
• Jeroen Bosch Ziekenhuis: collaborator

Study Sites (2)

Jeroen Bosch Hospital

's-Hertogenbosch, Netherlands

Location

St. Antonius Hospital

Nieuwegein, 3430EM, Netherlands

Location

Related Publications (3)

• van Rongen A, van der Aa MP, Matic M, van Schaik RHN, Deneer VHM, van der Vorst MM, Knibbe CAJ. Increased Metformin Clearance in Overweight and Obese Adolescents: A Pharmacokinetic Substudy of a Randomized Controlled Trial. Paediatr Drugs. 2018 Aug;20(4):365-374. doi: 10.1007/s40272-018-0293-1.

  PMID: 29748932 DERIVED

• van der Aa MP, Hoving V, van de Garde EM, de Boer A, Knibbe CA, van der Vorst MM. The Effect of Eighteen-Month Metformin Treatment in Obese Adolescents: Comparison of Results Obtained in Daily Practice with Results from a Clinical Trial. J Obes. 2016;2016:7852648. doi: 10.1155/2016/7852648. Epub 2016 Dec 22.

  PMID: 28101379 DERIVED

• van der Aa MP, Elst MA, van Mil EG, Knibbe CA, van der Vorst MM. METFORMIN: an efficacy, safety and pharmacokinetic study on the short-term and long-term use in obese children and adolescents - study protocol of a randomized controlled study. Trials. 2014 Jun 5;15:207. doi: 10.1186/1745-6215-15-207.

  PMID: 24899137 DERIVED

MeSH Terms

Conditions

Obesity; Insulin Resistance

Interventions

Metformin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• Marja MJ van der Vorst, MD, PhD

  St. Antonius Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Mrs. M.M.J. van der Vorst, paediatrician-clinical pharmacologist

Study Record Dates

• First Submitted: October 20, 2011
• First Posted: December 8, 2011
• Study Start: August 1, 2011
• Primary Completion: August 1, 2015
• Study Completion: February 28, 2017
• Last Updated: April 27, 2017

Record last verified: 2017-04

Locations

NL (2)