Semaglutide + Lifestyle Program for Obesity

(JOULE-MARS Trial)

Overseen By Athena Flores Miranda, BSc Health Sciences

Age: < 18

Sex: Any

Trial Phase: Phase 4

Sponsor: McMaster University

Must not be taking: Antidepressants, Antipsychotics, Beta-blockers, others

Disqualifiers: Diabetes, Mental health, Liver, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

74 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

Yes, you will need to stop taking certain medications. The trial excludes participants using specific medication classes, such as anti-psychotics, beta-blockers, and anti-hyperglycemic drugs, among others.

What data supports the effectiveness of the drug Semaglutide for obesity?

Research shows that Semaglutide, when combined with a lifestyle program, leads to significant weight loss in people with obesity. In clinical trials, participants lost an average of 14.9% to 17.4% of their body weight over 68 weeks, which is much more than those who did not receive the drug. ^{1 2 3 4 5}

Is semaglutide safe for weight management in humans?

Semaglutide is generally considered safe for weight management, with the most common side effects being mild-to-moderate stomach issues that usually go away on their own. Long-term studies have not raised new safety concerns, and it is well-tolerated compared to other similar treatments. ^{1 5 6 7 8}

How does the drug semaglutide combined with a lifestyle program differ from other obesity treatments?

Semaglutide, when combined with a lifestyle program, offers a unique approach to obesity treatment by using a once-weekly injection that significantly reduces body weight more effectively than other anti-obesity medications. It works by mimicking a hormone that regulates appetite and insulin, leading to greater weight loss and improved glucose metabolism, especially in individuals with prediabetes. ^{1 2 7 9 10}

What is the purpose of this trial?

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.

Research Team

Katherine M Morrison, MD FRCPC

Principal Investigator

McMaster University

Eligibility Criteria

The JOULE trial is for adolescents aged 12-17 with obesity, looking to manage their weight. Participants will join a behavioral lifestyle program and may also receive semaglutide injections. Those interested must be committed to the full duration of the study.

Inclusion Criteria

I am between 12 and 17 years old.

Diagnosed with obesity (BMI ≥2 standard deviations above WHO Reference median)

Enrolled in first six months of GHWM pediatric clinic (i.e. have at least one year of the program remaining)

Exclusion Criteria

Participation in any interventional clinical study within 90 days before screening

I have had bariatric surgery or a liver transplant.

I am currently taking medication for heart, diabetes, HIV, mental health, thyroid issues, nausea, or cough.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Behavioral Lifestyle Program (BLP) Alone

Group A participates in a behavioral lifestyle program alone for 6 months

6 months

Monthly visits (in-person)

BLP with Semaglutide

Group A continues with BLP and starts semaglutide treatment for an additional 6 months; Group B receives BLP and semaglutide from baseline for 6 months

6 months

Monthly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Treatment Details

Interventions

• Behavioural Lifestyle Program (BLP)
• Semaglutide

Trial Overview This study tests if adding semaglutide injections to a behavioral lifestyle program (BLP) affects metabolic adaptation during weight loss differently than BLP alone in obese adolescents over a period of up to 6 months.

Participant Groups

Group I: BLP and semaglutide Experimental Treatment 2 Interventions

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 .

Group II: BLP, then BLP+semaglutide Active Control 2 Interventions

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.

Who Is Running the Clinical Trial?

McMaster University

Lead Sponsor

Trials

936

Recruited

2,630,000+

Diabetes Canada

Collaborator

Trials

13

Recruited

1,200+

Canadian Institutes of Health Research (CIHR)

Collaborator

Trials

1,417

Recruited

26,550,000+

Findings from Research

In the STEP clinical trial program, participants with obesity who received once-weekly semaglutide 2.4 mg experienced significant weight loss, averaging between 14.9% and 17.4% over 68 weeks, with 69%-79% achieving at least 10% weight loss compared to only 12%-27% with placebo.

Semaglutide 2.4 mg also led to improvements in cardiometabolic risk factors and had a consistent safety profile, primarily involving gastrointestinal side effects, indicating its potential as an effective treatment for obesity and related health issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Semaglutide for the treatment of overweight and obesity: A review. Bergmann, NC., Davies, MJ., Lingvay, I., et al.[2023]

Semaglutide, a GLP-1 receptor agonist, has been shown to produce significant and sustained weight loss in adults with obesity, along with improvements in cardiometabolic risk factors, as demonstrated in the phase 3 STEP trials involving various participants.

The treatment is generally well tolerated, with the most common side effects being mild-to-moderate gastrointestinal issues that are usually temporary and do not require stopping the medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of semaglutide for weight management: evidence from the STEP program. Amaro, A., Sugimoto, D., Wharton, S.[2023]

Long-acting GLP-1 receptor agonists, such as liraglutide and semaglutide, are effective anti-obesity medications that can lead to significant weight loss, with semaglutide showing an average weight loss of 11.6% after one year, compared to 5.5% with liraglutide.

Both medications are generally well tolerated, with similar safety profiles, though they can cause transient gastrointestinal issues; ongoing long-term studies are needed to further evaluate their efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Benefit-Risk Assessment of Obesity Drugs: Focus on Glucagon-like Peptide-1 Receptor Agonists. Christensen, RM., Juhl, CR., Torekov, SS.[2020]

In a meta-analysis of six randomized controlled trials involving 3962 overweight or obese individuals, subcutaneous semaglutide 2.4 mg administered weekly resulted in significant and sustainable weight loss, with an average reduction of 11.8% in body weight compared to placebo.

Semaglutide was well tolerated, with the most common side effects being mild to moderate gastrointestinal issues, indicating a favorable safety profile for non-diabetic overweight or obese individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of semaglutide 2.4 mg for weight loss in overweight or obese adults without diabetes: An updated systematic review and meta-analysis including the 2-year STEP 5 trial. Qin, W., Yang, J., Deng, C., et al.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

Semaglutide 2.4-mg injection as a novel approach for chronic weight management. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Changes in Glucose Metabolism and Glycemic Status With Once-Weekly Subcutaneous Semaglutide 2.4 mg Among Participants With Prediabetes in the STEP Program. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Effect of semaglutide 2.4 mg once weekly on 10-year type 2 diabetes risk in adults with overweight or obesity. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Semaglutide for the treatment of overweight and obesity: A review. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Two-year effects of semaglutide in adults with overweight or obesity: the STEP 5 trial. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of semaglutide for weight management: evidence from the STEP program. [2023]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Benefit-Risk Assessment of Obesity Drugs: Focus on Glucagon-like Peptide-1 Receptor Agonists. [2020]

8. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of semaglutide 2.4 mg for weight loss in overweight or obese adults without diabetes: An updated systematic review and meta-analysis including the 2-year STEP 5 trial. [2023]

9. Switzerland pubmed.ncbi.nlm.nih.gov

The Impact Once-Weekly Semaglutide 2.4 mg Will Have on Clinical Practice: A Focus on the STEP Trials. [2022]

10. China pubmed.ncbi.nlm.nih.gov

New practice in semaglutide on type-2 diabetes and obesity: clinical evidence and expectation. [2022]