Metformin Intervention in children and adolescents with obesity. A parallel, three arms, randomized, 6 months, multi-center study with metformin extended release (XR) plus lifestyle or metformin immediate release (IR) plus lifestyle or lifestyle alone.

Phase 2

Completed

• Conditions: Children and Adolscents with obesity.

• Registration Number: 2024-517787-29-00
• Lead Sponsor: Region Uppsala

Brief Summary

To compare the effect between metformin extended release (XR) plus

lifestyle, and lifestyle alone on the BMI-SDS change, from baseline to the

6 months visit at end of treatment.

Detailed Description

Not available

Study Timeline

• Study First Posted: 2024-10-08
• Last Update Posted: 2024-10-08

Recruitment & Eligibility

• Status: Ended
• Sex: Not specified
• Target Recruitment: 90

Inclusion Criteria

Signed informed consent prior to any study-specific procedures.

Males or females of age 6 to less than 17 years and 3 months at the time of signing informed consent.

Body weight ≥ 40 kg.

Obesity (BMI-SDS >2.0) according to WHO.

Stable body weight during previous 90 days before screening visit 1 (< 5kg measured or self-reported weight change).

If female of childbearing potential: Not sexually active or usage of adequate anticonception and having negative pregnancy tests. Methods that can achieve a failure rate of less than 1% per year (Pearl index <1), when used consistently and correctly, are considered as highly effective birth control methods. Such methods include: •Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation: oral, intravaginal, transdermal. •Progestogen-only hormonal contraception associated with inhibition of ovulation: oral, injectable, implantable. •Intrauterine device (IUD). • Intrauterine hormone-releasing system (IUS). • Bilateral tubal occlusion. • Vasectomised partner. • Sexual abstinence (if refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. The reliability of sexual abstinence needs to be evaluated in relation to the preferred and usual lifestyle).

Exclusion Criteria

Known syndromal obesity (e.g. Prader-Willi syndrome, Bardet-Biedl syndrome or Laurence-Moon syndrome).

Severe sleep apnea, as judged by investigator.

Chronic disease, as judged by investigator.

Any concomitant medication influencing blood glucose (e.g. metformin and acarbose), influencing other parameters of metabolic syndrome (e.g. orlistat) or interfering with the investigational medicinal product from 3 months prior to screening until the end of the treatment period at visit 11.

Steroid treatment (oral or injected).

Antidepressants that can lead to weight gain, as judged by investigator.

Unstable treatment for neuropsychiatric disorders such as ADHD/ADD, and/or treatment started within 3 months prior to screening visit.

Known hypersensitivity to metformin or any of the excipients.

Language difficulties, impaired mental ability or not willing to understand or comply with the study procedures.

Participation in another clinical study involving an Investigational Medicinal Product (IMP) within three months prior to screening.

Subject from the same household participating in this trial.

Pregnancy or lactation.

Indigestion-causing diseases.

Severe gastrointestinal disease, as judged by investigator.

Total or partial gastric or small intestine resection.

Type 1 diabetes mellitus.

Kidney disease or renal dysfunction, acute or chronic (eGFR <60ml/min/1,73m2 ).

Hypo-/hyperthyroidism, unless stable treatment.

Severe depression, severe anxiety or other psychiatric disorder referred to or undergoing special treatment, as judged by investigator.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
BMI-SDS (according to WHO).		BMI-SDS (according to WHO).

Secondary Outcome Measures

Name	Time	Method
1 and 3: BMI-SDS (according to WHO).		1 and 3: BMI-SDS (according to WHO).
2. Adverse Events, vital signs (systolic and diastolic blood pressure (SBP and DBP) and heart rate), physical examination, fP-glucose, ALAT, creatinine, lactate, cobalamin, clinical chemistry, haematology and urine analysis and plasma metformin concentration.		2. Adverse Events, vital signs (systolic and diastolic blood pressure (SBP and DBP) and heart rate), physical examination, fP-glucose, ALAT, creatinine, lactate, cobalamin, clinical chemistry, haematology and urine analysis and plasma metformin concentration.
4. Plasma and urine concentration of metformin (PK), area under the curve (AUC), BMI-SDS (according to WHO).		4. Plasma and urine concentration of metformin (PK), area under the curve (AUC), BMI-SDS (according to WHO).
5. Demographics, tanner stage, anthropometrics and growth chart. Plasma and urine concentration of metformin (PK), area under the curve (AUC) and BMI-SDS (according to WHO).		5. Demographics, tanner stage, anthropometrics and growth chart. Plasma and urine concentration of metformin (PK), area under the curve (AUC) and BMI-SDS (according to WHO).
6. Glucose and insulin at fasting and during OGTT. Insulin secretion and sensitivity derived from OGTT. HbA1c.		6. Glucose and insulin at fasting and during OGTT. Insulin secretion and sensitivity derived from OGTT. HbA1c.
7. Triglycerides, Total cholesterol, High-Density Lipoprotein (HDL), Low-Density Lipoprotein (LDL), SBP and DBP.		7. Triglycerides, Total cholesterol, High-Density Lipoprotein (HDL), Low-Density Lipoprotein (LDL), SBP and DBP.
8. Creatinine, Cystatin C/GFR, Alanine Aminotransferase (ALAT), Gamma Glutamyl Transpeptidase (GGT), Lactate Dehydrogenase (LD) and Bilirubin.		8. Creatinine, Cystatin C/GFR, Alanine Aminotransferase (ALAT), Gamma Glutamyl Transpeptidase (GGT), Lactate Dehydrogenase (LD) and Bilirubin.
9. Hs-CRP.		9. Hs-CRP.
10. IGF-1, SHBG, FSH, LH, Testosterone and Estrogen.		10. IGF-1, SHBG, FSH, LH, Testosterone and Estrogen.
11. Anthropometrics, waist- and hip circumference (including ratio), and sagittal abdominal diameter (SAD). Bioimpedance, indirect calorimetry and skin fold measurement will be performed at selected sites		11. Anthropometrics, waist- and hip circumference (including ratio), and sagittal abdominal diameter (SAD). Bioimpedance, indirect calorimetry and skin fold measurement will be performed at selected sites
12. Questionnaires: Food Frequency (FFQ), Regular meals, Portion Size, Physical Activity, Medipal®.		12. Questionnaires: Food Frequency (FFQ), Regular meals, Portion Size, Physical Activity, Medipal®.
13. PedsQL™.		13. PedsQL™.

Trial Locations

Locations (2)

Region Dalarna; 🇸🇪 Falun, Sweden

Uppsala University Hospital; 🇸🇪 Uppsala, Sweden

Region Dalarna

🇸🇪Falun, Sweden

Björn Persson

Site contact

+4623490000

bjorn.persson@regiondalarna.se