E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10029885 |
E.1.2 | Term | Obesity, unspecified |
E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
A) To treat young adults with childhood-onset obesity, who have been resistant to structured lifestyle intervention (TCOC protocol), with the GLP-1 RA semaglutide (Wegovy®). B) To treat young adults with childhood-onset obesity, who have responded to the structured lifestyle intervention (TCOC protocol) and still have obesity, with the same GLP-1 RA, semaglutide (Wegovy®). C) To identify underlying mechanisms of lifestyle-untreatable versus treatable childhood-onset obesity. D) Assess the efficacy of an exercise-based strategy to discontinue obesity medication while sustaining a healthy body composition in youth with childhood-onset obesity
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E.2.2 | Secondary objectives of the trial |
Determine the effect of a GLP-1 receptor agonist on body composition and metabolic health in young adults with obesity |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Age 18-28 years • Group A: BMI≥30. Non-responders: No BMI SDS reduction (<0.1 BMI SDS) during TCOC protocol for more than one year and still have obesity. • Group B: BMI≥30. Insufficient responders: BMI SDS reduction >0.25 BMI SDS during TCOC protocol for more than one year, but still have obesity. • Group C: BMI<30. Excellent responders: BMI SDS reduction >0.5 BMI SDS during TCOC protocol for more than one year and no longer have obesity (BMI<30). • Group D : Young adults who have participated in The Holbaek Study and have had normal weight development during childhood. • The period from the initial treatment with TCOC protocol until inclusion in the study must be within 15 years.
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E.4 | Principal exclusion criteria |
• Patients diagnosed with known serious chronic illness including type 1 or 2 diabetes (or a randomly measured fasting plasma glucose > 7 mmol/l) • Angina pectoris, coronary heart disease, congestive heart failure (NYHA III-IV) • Severe renal impairment (creatinine clearance (GFR) <30 mL/min) • Severe hepatic impairment • Inflammatory bowel disease • Diabetic gastroparesis • Cancer • Chronic obstructive lung disease • Severe psychiatric disease, a history of major depressive or other severe psychiatric disorders • The use of medications that cause clinically significant weight gain or loss • Previous bariatric surgery • A history of idiopathic acute pancreatitis • A family or personal history of multiple endocrine neoplasia type 2 or familial medullary thyroid carcinoma • Pregnancy, expecting pregnancy or breastfeeding. If a study participant is in doubt whether she could be pregnant, a urine pregnancy test is performed. Women with reproductive potential who are not using adequate contraceptive methods (combined oral contraceptive pill, progestin-only contraceptive pill, condoms, intrauterine device, injection, implant, or sterilization). Adequate contraception must be used throughout the study period and at least 2 months after discontinuation of trial medication (semaglutide will be present in the circulation for 5-7 weeks after the last dose). • Allergy to any of the ingredients/excipients of the study medication: semaglutide, disodium phosphate dihydrate, propylene glycol, phenol, hydrochloric acid, sodium hydroxide. • Exclusion criteria for MRI : Pacemaker, claustrophobia, metal splinters or any other magnetic devices that cannot be removed prior to the scan (Participants can join the trial without MR scan). |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in BMI from before to after GLP-1 RA treatment compared to placebo |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1) Body composition 2) Body weight 3) Metabolic health (glucose tolerance and lipid status, waist circumference, blood pressure, Composite Metabolic syndrome Z-score) 4) liver fat 5) weight loss induced bone loss 6) appetite regulation 7) systemic markers of immuno-metabolism 8) immuno-metabolic profile of adipose tissue 9) circulating inflammatory cells (PBMCs) 10) food preferences and appetite sensation 11) genetic risk scores 12) microbiota 13) metabolomics |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |