obese children and adolescents of Caucasian descent with insulin resistance in the age of = 10 and = 16 years at study entry.
Conditions
Interventions
Trade Name: Metformin
Product Name: Metformin
Product Code: A10BA02
Pharmaceutical Form: Tablet
Pharmaceutical form of the placebo: Coated tablet
Route of administration of the placebo: Oral use
Sponsors
St. Antonius Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: The inclusion criteria are subject’s age = 10 and = 16 years at study entry, from Caucasian descent, with obesity defined as BMI-SDS > 2.3 and with insulin resistance defined as HOMA-IR = 3.4. In addition an obtained informed consent from subjects and parents/caregivers. Are the trial subjects under 18? yes Number of subjects for this age range: 144 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: The exclusion criteria are presence of T2DM (American Diabetes Association criteria); presence of endocrine disorders with steroid therapy; suspicion of polycystic ovarium syndrome; height 150% of normal value for age); use of ritonavir; use of ACE inhibitors; insufficient knowledge of the Dutch language.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the METFORMIN study is to determine the efficacy of metformin in combination with lifestyle-intervention in obese children and adolescents with insulin resistance versus placebo with lifestyle-intervention. ;Secondary Objective: The secondary objective of the METFORMIN study is to determine the safety and tolerability of metformin in combination with lifestyle-intervention in obese children and adolescents with insulin resistance versus placebo with lifestyle-intervention. The tertiary objective of the METFORMIN study is to study the population pharmacokinetics (PK) of metformin in obese children and adolescents. The quaternary objective of the METFORMIN study is to determine the long-term efficacy and long-term safety and tolerability of metformin in obese children and adolescents with insulin resistance. Other objectives are to compare values of body fat measured using bio-impedance with values of body fat measured using dual energy X-ray absorptiometry (DEXA scan), and to compare insulin sensitivity measured by the whole body insulin sensitivity index (WBISI) with insulin sensitivity calculated by Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) in obese children and adolescents. ;Primary end point(s): Primary study endpoint for efficacy is the reduction in BMI, which is calculated from the anthropometric measurements. Other primary endpoints for efficacy are insulin resistance, calculated by the HOMA-IR, percentage of body fat measured by bio-impedance, HbA1C, ß-cell function, calculated by HOMA-ß%, oral disposition index, insulin secretion calculated by the insulinogenic index, physical fitness measured by validated fitness tests and quality of life measured by validated quality of life questionnaire. ;Timepoint(s) of evaluation of this end point: Evaluation of primary study point will be performed at t=18 months and t=36 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary outcome parameters for safety of metformin treatment are hepatic and renal function tests, and for tolerability the number of adverse effects (in relation to the achieved dose level). Tertiary outcome parameters are the PK parameters of metformin in obese children and adolescents. These parameters are estimated using population PK-PD modelling techniques in which a comprehensive covariate analysis will be performed allowing to account for variability in PK parameters on the basis of individual characteristics such as age, bodyweight, BMI, percentage of body fat, gender, Tanner stage and genetic constitution. Quaternary outcome parameters for long-term efficacy and long-term safety and tolerability of metformin are BMI, insulin resistance calculated by the HOMA-IR, percentage of body fat measured by bio-impedance, HbA1C, ß-cell function, calculated by HOMA-ß%, oral disposition index, insulin secretion calculated by the insulinogenic index, physical fitness measured by validated fitness tests, quality of life measured by validated quality of life questionnaire, hepatic and renal function tests and number of side effects. In addition, the percentage of patients that has developed impaired fasted glucose, impaired glucose tolerance (2-hrs plasma glucose during an OGTT), T2DM and the development of micro-vascular complications detected by micro-albuminuria and macro-vascular complications detected by using pulse wave velocity (PWV) and augmentation index (AIx) is evaluated. ;Timepoint(s) of evaluation of this end point: Evaluation of secondary endpoint parameters will be performed at t=18 months and t=36 months Evaluation of teriary endpoint parameters will be performed at t=18 months Evaluation of quaternary endpoint parameters will be performed at t=36 months | — |
Countries
Netherlands
Contacts
Public ContactDhr. Drs. A.J. Meinders
St. Antonius hospital
Outcome results
None listed