JOULE - Metabolic Adaptation to Weight Loss in Response to a Behavioural Lifestyle Program With or Without Semaglutide in Adolescents With Obesity

NCT06852391 | Recruiting Phase 4

• 1 other identifier: 18026
• Study Type: interventional
• Target: 74
• Locations: 1 country
• Sites: 1

Brief Summary

The Joule MARS study is a single center, randomized, open label clinical trial aiming to explore the metabolic adaptations that occur in response to weight management in adolescents with obesity. Behavioural lifestyle intervention with and without a pharmacological intervention - semaglutide- will be studied. Study participants will be randomized to one of two groups. Group A will follow a behavioral lifestyle program (BLP) alone for 6 months, followed by BLP and treatment with semaglutide for six months. Group B will be enrolled in BLP and semaglutide from baseline to 6 months. The primary research question will assess, in youth aged 12-17 years diagnosed with obesity and enrolled in a weight management program, if the implementation of a BLP together with semaglutide, compared to the implementation of BLP alone for 6 months leads to less adaptive thermogenesis.

Conditions

Obesity (Disorder)

Keywords

Adaptive Thermogenesis; obesity; semaglutide; GLP-1 agonist; weight loss; Energy expenditure; Whole room calorimetry; MRI; MR elastography; Cold exposure; Liver stiffness; Brown adipose tissue; Pediatric; Quality of life

Outcome Measures

Primary Outcomes (1)

• Measurement of Adaptive thermogenesis

  Adaptive thermogenesis will be calculated as the difference between measured and predicted REE after the intervention. Measured REE will be assessed with the participant awake, but at rest, in a whole room indirect calorimeter. Predicted REE will be calculated based on an equation derived using baseline data from this study population as is currently recommended. Variables that will be considered in deriving the equation include fat-free mass, fat mass, age and sex. We will compare adaptive thermogenesis (primary outcome) and work efficiency between the two treatments utilizing linear regression analysis. Separate analyses for males and females will ensure relevance of study findings to both sexes.

  6, 12 months

Secondary Outcomes (10)

• Changes in energy work efficiency from baseline during standardized exercise

  Baseline, 6, 12 months

• Brown Adipose Tissue (BAT) activity

  From enrollment to 6 months and to 12 months

• Health-related quality of life (HRQoL)

  Baseline to 6 months and to 12 months

• Total body mass, fat mass and lean mass

  Baseline, 6, 12 months

• Hepatic fat content

  Baseline, 6, 12 months

Study Arms (2)

BLP, then BLP+semaglutide

ACTIVE COMPARATOR

Group A will engage in a BLP alone for the first six months of the study, then receive BLP and semaglutide (Wegovy®) for the last six months of the study, beginning with 0.25 mg subcutaneously weekly and being titrated every four weeks up to a maximum of 2.4 mg in approved doses 0.25 mg, 0.5 mg, 1 mg, 1.7 mg, 2.4 mg.

Drug: Semaglutide Pen Injector; Behavioral: Behavioural Lifestyle Program (BLP)

BLP and semaglutide

EXPERIMENTAL

In addition to BLP, Group B will receive semaglutide (Wegovy®) titrated to maximal dose tolerated, in approved doses of 0.25 mg, 0.5 mg, 1 mg, 1.7 mg, 2.4 mg subcutaneously weekly for 6 months .

Drug: Semaglutide Pen Injector; Behavioral: Behavioural Lifestyle Program (BLP)

Interventions

Semaglutide Pen Injector DRUG

Semaglutide will be delivered by a subcutaneous injection using an injectable pen once weekly. Semaglutide is formulated with 5 approved doses (0.25 mg, 0.5 mg, 1 mg, 1.7 mg, 2.4 mg). Treatment will commence with the lowest dose and will be increased every 4 weeks to the maximum tolerable dose where they will remain for the remainder of the treatment. Participants who are taking the drug will have monthly visits to assess any adverse events, dose titration and drug adherence.

Also known as: Wegovy®

BLP and semaglutide; BLP, then BLP+semaglutide

Behavioural Lifestyle Program (BLP) BEHAVIORAL

The BLP will be delivered by the Growing Healthy Weight Management (GHWM) pediatric program at McMaster Children's Hospital. GHWM is a family-based program addressing health behaviours (nutritional pattern and eating behaviours, physical activity, sedentary time and sleep) and physical and mental health issues. In Year 1, the program typically includes 2 group sessions and monthly individualized sessions with the participant and their family. The interdisciplinary weight management team is comprised of a registered dietician, exercise physiologist, kinesiologist, social worker and/or psychologist, general pediatrician and pediatric endocrinologists.

BLP and semaglutide; BLP, then BLP+semaglutide

Eligibility Criteria

• Age: 12 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Youth aged 12-17 years
• Diagnosed with obesity (BMI ≥2 standard deviations above WHO Reference median)
• Enrolled in Growing Health Weight Management or Next Step pediatric clinics (ie. have at least one year of the program remaining).

You may not qualify if:

• Any contraindications for MRI (i.e. claustrophobia, implanted metal, metallic injuries recent tattoo or weight \>300lb. Ineligible for imaging visit only.
• Use of atypical anti-psychotics.
• Use of the following medication classes: (i.e. Beta-blocker medications, Steatogenic medications, Anti-hyperglycemic medications, HIV drugs, Antidepressants, anxiolytic drugs, anti-psychotic drugs, Thyroid drugs, Antiemetic or amphetamine, dextromethorphan and metoclopramide.)
• Elevated alanine aminotransferase (ALT) \> 5 x upper range of normal at screening.
• Use of glucose lowering or any anti-obesity medication in the previous 3 months.
• Known monogenic, syndromic or hypothalamic causes of obesity.
• Diagnosis of type 1 or 2 diabetes mellitus.
• Prior bariatric surgery or liver transplantation.
• Alcohol intake exceeding 3 drinks per week or reported cannabis use.
• Recent history of cigarette smoking (previous 3 months) - ineligible for imaging only.
• History or family history of multiple endocrine neoplasia 2 or medullary thyroid cancer.
• History of pancreatitis.
• Presence of untreated endocrine disorder.
• History of an eating disorder and / or history of suicidal ideation
• History of a cardiac condition that precludes exercise testing or unable to have exercise testing done in the GHWM pediatric clinic, inability to use a cycle ergometer.

Sponsors & Collaborators

• McMaster University: lead
• Diabetes Canada: collaborator
• Canadian Institutes of Health Research (CIHR): collaborator

Study Sites (1)

McMaster University

Hamilton, Ontario, L8S 4L8, Canada

RECRUITING

MeSH Terms

Conditions

Obesity; Weight Loss

Interventions

semaglutide

Condition Hierarchy (Ancestors)

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

Study Officials

• Katherine M Morrison, MD FRCPC

  McMaster University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Athena Flores Miranda

CONTACT

905-525-9140; joulemrs@mcmaster.ca

Aaron Thomas, PhD

CONTACT

905-525-9140; joulemrs@mcmaster.ca

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 6, 2025
• First Posted: February 28, 2025
• Study Start: June 18, 2025
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: January 14, 2026

Record last verified: 2026-01

Locations

CA (1)