Clinical trial NCT01487993: Metformin in Obese Children and Adolescents
Official title: An Efficacy, Safety and Pharmacokinetic Study on the Short-term and Long-term Use of Metformin in Obese Children and Adolescents
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Obesity
Insulin Resistance
Keywords: Obesity
Children
Adolescents
Metformin
Insulin resistance
Lead sponsor: St. Antonius Hospital
Sponsor class: OTHER
Collaborators: name: Jeroen Bosch Ziekenhuis
First posted: 2011-12-08
Enrollment: 62
Sex: ALL
Minimum age (years): 10
Maximum age (years): 16
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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 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.

Primary outcomes:
measure: Change in BMI from baseline
timeFrame: 18 months and 36 months
measure: Change in Insulin resistance from baseline
timeFrame: 3; 6; 9; 12; 15; 18; 24; 30 and 36 months
Secondary outcomes:
measure: Renal and hepatic function
timeFrame: 3; 6; 9; 12; 15; 18; 24; 30 and 36 months
measure: Tolerability
timeFrame: 3; 6; 9; 12; 15; 18; 24; 30 and 36 months
measure: Pharmacokinetics (PK)-parameters: clearance (ml/min)
timeFrame: 9 months
measure: Body fat percentage
timeFrame: 0, 9, 18 and 36 months
measure: Physical fitness
timeFrame: 0, 9, 18 and 36 months
measure: Quality of life
timeFrame: 0, 9, 18 and 36 months
measure: Long term efficacy
timeFrame: 36 months
measure: Long-term safety
timeFrame: 36 months
measure: Long-term tolerability
timeFrame: 36 months
measure: Microvascular complications
timeFrame: 36 months
measure: Macrovascular complications
timeFrame: 36 monthts
measure: Development of T2DM
timeFrame: 36 months
measure: PK-parameters: volume of distribution (liters)
timeFrame: 9 months
Other outcomes:
Locations:
city: 's Hertogenbosch
country: Netherlands
facility: Jeroen Bosch Hospital
city: Nieuwegein
country: Netherlands
facility: St. Antonius Hospital
Study officials:
affiliation: St. Antonius Hospital
name: Marja MJ van der Vorst, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.