Young Adults With Early-onset Obesity Treated With Semaglutide

NCT05574439 | Completed Phase 4 DMC

• 2 other identifiers: U1111-1215-86062019-002274-31
• Study Type: interventional
• Target: 246
• Locations: 1 country
• Sites: 2

Brief Summary

Introduction: The increasing prevalence of obesity is particularly pronounced among adolescents. Currently available treatment options consist of structured lifestyle interventions. However, 25 % of adolescents do not respond to lifestyle treatment, why new effective treatment strategies are needed. Therefore, the aim of this study is to investigate the effect of lifestyle interventions combined with the GLP-1 receptor agonist semaglutide to young adults with otherwise treatment resistant obesity. Methods and analysis: This is an investigator-initiated, randomized, placebo-controlled trial. 180-270 young adults (age 18-28) will be recruited from The Childrens Obesity Clinic (TCOC), Department of Pediatrics, Holbæk Hospital. Based on their previous response to the TCOC protocol the participants will be divided in four groups: Group A: Non-responders: 55-85 young adults with obesity (BMI≥30 kg/m2) who have not reduced adiposity, defined as BMI SDS reduction \<0.1, during the structured lifestyle counselling as children. Group B: Insufficient responders: 55-85 young adults who have reduced adiposity, defined as BMI SDS reduction \>0.25, during the structured lifestyle counselling as children but still have obesity as young adults (BMI≥30 kg/m2) Group C: Excellent responders: 35-50 young adults, who have reduced adiposity, defined as BMI SDS reduction \>0.5, during the structured lifestyle counselling as children and no longer have obesity as young adults (BMI\<30 kg/m2) Group D: Population-based reference group (normal weight development): 35-50 young adults, who have participated in The Holbaek Study as children. Group A and B are randomized 2:1 to either semaglutide or placebo for 68 weeks. Group C and D will attend baseline examinations only and not undergo intervention. The primary endpoint is change in BMI from randomization to end-of-treatment. Ethics and dissemination: The trial has been approved by the Danish Medicines Agency (EudraCT 2019-002274-31) and by the ethical committee of the Capital Region of Denmark (H-20039422). The trial will be conducted in agreement with the Declaration of Helsinki and monitored to follow the guidelines for good clinical practice. Results will be submitted for publication in international peer-reviewed scientific journals.

Conditions

Obesity, Adolescent

Keywords

GLP-1 RA; Semaglutide; Weight loss; Treatment resistant

Outcome Measures

Primary Outcomes (1)

• Change in BMI (weight in kg/height in m^2)

  Weight will be measured to the nearest 0.1 kg. The same set of scales should ideally be used throughout the trial. Weight should be measured in a fasting state without shoes and wearing light indoor clothes. Height will be measured to the nearest 0.1 cm.

  Change from baseline to end-of-treatment (68 weeks)

Secondary Outcomes (9)

• Change in body composition (fat mass)

  Change from baseline to end-of-treatment (68 weeks)

• Change in body composition (fat percentage)

  Change from baseline to end-of-treatment (68 weeks)

• Change in body composition (fat free mass)

  Change from baseline to end-of-treatment (68 weeks)

• Change in visceral fat and liver fat

  Change from baseline to end-of-treatment (68 weeks)

• Change in metabolic syndrome

  Change from baseline to end-of-treatment (68 weeks)

Other Outcomes (44)

• HOMA-IR

  Baseline comparison and change from baseline to end-of-treatment (68 weeks)

• Matsuda Index

  Baseline comparison and change from baseline to end-of-treatment (68 weeks)

• Plasma Glucose

  Baseline comparison and change from baseline to end-of-treatment (68 weeks)

Study Arms (5)

Non-responders: TCOC+ semaglutide

ACTIVE COMPARATOR

Semaglutide: 2.4 mg/week SC, concentration: 3.0 mg/ml) in combination with TCOC treatment (i.e. diet/weight consultations).

Behavioral: TCOC treatment; Drug: Semaglutide 3 mg/ml

Non-responders: TCOC+ placebo

PLACEBO COMPARATOR

Placebo: 2.4 mg/week SC in combination with TCOC treatment (i.e. diet/weight consultations).

Behavioral: TCOC treatment; Drug: Placebo (Semaglutide 3 mg/ml)

Insufficient responders: TCOC+ semaglutide

ACTIVE COMPARATOR

Semaglutide: 2.4 mg/week SC, concentration: 3.0 mg/ml) in combination with TCOC treatment (i.e. diet/weight consultations).

Behavioral: TCOC treatment; Drug: Semaglutide 3 mg/ml

Insufficient responders: TCOC+ placebo

PLACEBO COMPARATOR

Placebo: 2.4mg/week SC in combination with TCOC treatment (i.e. diet/weight consultations).

Behavioral: TCOC treatment; Drug: Placebo (Semaglutide 3 mg/ml)

Excellent Responders and Population-based reference group

NO INTERVENTION

No intervention.

Interventions

TCOC treatment BEHAVIORAL

The TCOC protocol is a chronic care, family-based and multidisciplinary childhood obesity treatment program involving behavior-changing techniques, based on current guidelines for best-practice and authoritative recommendations involving a multidisciplinary tertiary team of health care professionals.

Insufficient responders: TCOC+ placebo; Insufficient responders: TCOC+ semaglutide; Non-responders: TCOC+ placebo; Non-responders: TCOC+ semaglutide

Semaglutide 3 mg/ml DRUG

Participants will be instructed to initiate at 0.24 mg SC once weekly for 4 weeks, and in 4 week intervals, increase the dose until a dose of 2.4 mg is reached. In case of prolonged side effects the dose may be adjusted to lower than 2.4mg/week.

Insufficient responders: TCOC+ semaglutide; Non-responders: TCOC+ semaglutide

Placebo (Semaglutide 3 mg/ml) DRUG

Participants will be instructed to initiate at 0.24 mg SC once weekly for 4 weeks, and in 4 week intervals, increase the dose until a dose of 2.4 mg is reached. In case of prolonged side effects the dose may be adjusted to lower than 2.4mg/week.

Insufficient responders: TCOC+ placebo; Non-responders: TCOC+ placebo

Eligibility Criteria

• Age: 18 Years - 28 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.
• Group D: Young adults who have participated in The Holbaek Study and have had normal weight development during childhood

You may not qualify if:

• Participants 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
• Use of medications causing 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.

Sponsors & Collaborators

• Signe Torekov: lead
• University of Leeds: collaborator
• Karolinska Institutet: collaborator
• Holbaek Sygehus: collaborator
• Rigshospitalet, Denmark: collaborator

Study Sites (2)

Holbæk University Hospital

Holbæk, Region Zeeland, 4300, Denmark

Location

University of Copenhagen, Department of Biomedical Sciences

Copenhagen, 2200, Denmark

Location

Related Publications (23)

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MeSH Terms

Conditions

Pediatric Obesity; Weight Loss

Interventions

semaglutide

Condition Hierarchy (Ancestors)

Obesity; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Body Weight Changes

Study Officials

• Signe S Torekov, Prof, PhD

  University of Copenhagen

  STUDY DIRECTOR

• Jens-Christian Holm, Ass. Prof, PhD

  Holbæk University Hospital

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The above-mentioned are masked in terms of semaglutide/placebo. Statistical analysis of primary outcome will be blinded to the assessor.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Model Details: Four groups will be identified based on their previous response to structured lifestyle interventions. Non-responders (group A) and insufficient responders (group B) are randomized 2:1 to either Semaglutide 2.4 mg/ week sc or placebo for 68 weeks. Group C (excellent responders) and Group D (population-based reference group with normal weight development) will attend baseline examinations only and not undergo intervention.

Study Record Dates

• First Submitted: October 6, 2022
• First Posted: October 10, 2022
• Study Start: June 1, 2022
• Primary Completion: April 1, 2026
• Study Completion: April 1, 2026
• Last Updated: May 4, 2026

Record last verified: 2026-04

Locations

DK (2)