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

Official title

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

Overview

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.

Detailed description

The Joule MARS (Metabolic Adaptation to weight loss in Response to a behavioural lifestyle program with or without Semaglutide in adolescents with obesity) study is a single-center, randomized controlled trial designed to investigate the effects of a behaviour lifestyle program and the medication semaglutide on resting energy expenditure (REE), work efficiency during standard exercise on a cycle ergometer and related metabolic outcomes in adolescents with obesity. The study will involve two intervention groups:

Group A will participate in a behavioral lifestyle program (BLP) alone for 6 months followed by a combination of semaglutide treatment and a BLP for an additional 6 months.

Group B will receive semaglutide and a BLP for the first 6 months and then terminate the study.

The study objectives are to determine if, in youth aged 12-17 years with obesity and enrolled in a weight management program:

1. the implementation of a BLP and semaglutide, compared to the implementation of a BLP alone leads to less adaptive thermogenesis (AT) at 6 months; 2. the implementation of a BLP and semaglutide, compared to the implementation of a BLP alone for 6-month, leads to:

Less increase in energy work efficiency during standardized exercise

Differences in BAT activity

Differences in health-related quality of life (HRQoL) 3. BLP and semaglutide, compared to BLP alone, lead to improvements in metabolic health measures (including lipids, glycemia, liver enzymes, hepatic fat and hepatic stiffness) after 6 months. 4. A longer time enrolled in BLP prior to addition of 6 months of semaglutide alters health outcome response to semaglutide.

A comprehensive assessment will be conducted throughout the study. Using whole-room indirect calorimetry, REE and muscle work efficiency, evaluated during standardized physical activity on a cycle ergometer, will be measured. Body composition (Dual energy x-ray absorptiometry and bioelectric impedance analysis), anthropometry (height, weight, waist circumference, BMI, BMI z score (WHO)), metabolic health, health related quality of life, hepatic fat and cold induced brown adipose tissue activity (MRI) will be assessed. Randomization will be managed via the REDCap EDC system.

Interventions

• Drug Semaglutide Pen Injector
  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.
• Behavioral Behavioural Lifestyle Program (BLP)
  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 compr

Primary outcome measures

• Measurement of Adaptive thermogenesis [Time frame: 6, 12 months]

Secondary outcome measures (10)

• Changes in energy work efficiency from baseline during standardized exercise [Time frame: Baseline, 6, 12 months]
• Brown Adipose Tissue (BAT) activity [Time frame: From enrollment to 6 months and to 12 months]
• Health-related quality of life (HRQoL) [Time frame: Baseline to 6 months and to 12 months]
• Total body mass, fat mass and lean mass [Time frame: Baseline, 6, 12 months]
• Hepatic fat content [Time frame: Baseline, 6, 12 months]
• Hepatic stiffness [Time frame: Baseline, 6 and 12 months]
• Fasting lipid profile [Time frame: Baseline, 6, 12 months]
• Fasting insulin [Time frame: Baseline, 6, 12 months]
• Hemoglobin A1C [Time frame: Baseline, 6 and 12 months]
• Alanine aminotransferase [Time frame: Baseline, 3, 6, 9 and 12 months]

Eligibility criteria

Inclusion criteria

• 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).

Exclusion criteria

• 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.

Participant who does not have a peak power value obtained in the GHWM pediatric clinic

Female who is pregnant, breast-feeding or intends to become pregnant.

Female who refuses to use a means of contraception if sexually active.

Participation in any interventional clinical study within 90 days before screening.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Canada · 1 center

• McMaster University — Hamilton

Identifiers

NCT: NCT06852391 · 18026

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗