Metformin in Obese Children and Adolescents | RxWiki

Metformin in Obese Children and Adolescents

Overview[ - collapse ][ - ]

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	Obesity Insulin Resistance
Intervention	Drug: Metformin Behavioral: Lifestyle intervention
Phase	Phase 3
Sponsor	St. Antonius Hospital
Responsible Party	St. Antonius Hospital
ClinicalTrials.gov Identifier	NCT01487993
First Received	October 20, 2011
Last Updated	August 21, 2013
Last verified	August 2013

Tracking Information[ + expand ][ + ]

First Received Date	October 20, 2011
Last Updated Date	August 21, 2013
Start Date	August 2011
Estimated Primary Completion Date	February 2017
Current 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).
Current 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.

Descriptive Information[ + expand ][ + ]

Brief Title	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
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.
Study Type	Interventional
Study Phase	Phase 3
Study Design	Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment
Condition	Obesity Insulin Resistance
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. Other Names: GlucophageBehavioral: Lifestyle intervention Lifestyle intervention: 18 months physical therapy and dietary advice
Study Arm (s)	Active Comparator: Metformin Metformin with lifestyle intervention during 18 months Placebo Comparator: Placebo Placebo and lifestyle intervention during 18 months

Recruitment Information[ + expand ][ + ]

Recruitment Status	Recruiting
Estimated Enrollment	144
Estimated Completion Date	February 2017
Estimated Primary Completion Date	August 2015
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.
Gender	Both
Ages	10 Years
Accepts Healthy Volunteers	No
Contacts	Contact: Marieke MAJ Elst, MD +31306093775 m.elst@antoniusziekenhuis.nl
Location Countries	Netherlands

Administrative Information[ + expand ][ + ]

NCT Number	NCT01487993
Other Study ID Numbers	Metformin 2011-6
Has Data Monitoring Committee	Yes
Information Provided By	St. Antonius Hospital
Study Sponsor	St. Antonius Hospital
Collaborators	Jeroen Bosch Ziekenhuis
Investigators	Principal Investigator: Marja MJ van der Vorst, MD, PhD St. Antonius Hospital
Verification Date	August 2013

Locations[ + expand ][ + ]

Jeroen Bosch Hospital	's Hertogenbosch, Netherlands Contact: Marieke AJ Elst, MD \| +31 30 609 3775 \| m.elst@antoniusziekenhuis.nl Principal Investigator: Edgar GAH van Mil, MD, PhD Recruiting
St. Antonius Hospital	Nieuwegein, Netherlands, 3430EM Contact: Marieke AJ Elst, MD \| +31306093775 \| m.elst@antoniusziekenhuis.nl Principal Investigator: Marja MJ van der Vorst, MD, PhD Recruiting