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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how a behavioral lifestyle program combined with semaglutide (a medication for weight management) affects weight management in adolescents with obesity. Researchers aim to determine if adding semaglutide to a lifestyle program yields better results than the lifestyle program alone. Participants will be divided into two groups: one will begin with the lifestyle program and add semaglutide later, while the other will use both from the start. Teens aged 12-17 diagnosed with obesity and enrolled in a weight management program may be suitable for this trial. As a Phase 4 trial, this study involves an FDA-approved treatment and seeks to understand how it can benefit more patients.

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 is the safety track record for these treatments?

Research has shown that semaglutide, a treatment under study for weight management, has undergone thorough testing in adults with obesity. In one study involving over 2,000 adults, 16.6% stopped using semaglutide due to side effects, compared to 8.2% who stopped when given a placebo (a substance with no active drug). These side effects led some participants to discontinue the treatment.

Semaglutide is already approved for weight management, indicating it is generally well-tolerated, though individual reactions can vary. Common side effects include nausea and vomiting, which are important to consider. It is essential to consult a healthcare provider about potential risks and benefits before starting a new treatment. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Unlike the standard obesity treatments, which typically focus on lifestyle changes alone, the combination of a Behavioral Lifestyle Program (BLP) with semaglutide offers a dual approach that targets weight loss more effectively. Semaglutide, a GLP-1 receptor agonist, is exciting because it works by mimicking a hormone that helps regulate appetite and food intake, potentially leading to significant weight loss. Researchers are particularly enthusiastic about its ability to be titrated to a maximum dose, allowing for personalized treatment that could enhance its effectiveness. This combination approach could offer a more comprehensive solution for obesity compared to lifestyle changes or medications alone.

What evidence suggests that this trial's treatments could be effective for obesity?

Research has shown that semaglutide, combined with lifestyle changes, can lead to significant weight loss. In this trial, participants in one arm will engage in a Behavioral Lifestyle Program (BLP) alone for the first six months, then receive both BLP and semaglutide for the last six months. Another arm will receive both BLP and semaglutide throughout the study. Previous studies have indicated that about 30% of adults taking semaglutide lost 20% or more of their body weight. One study found that a weekly dose of 2.4 mg helped patients maintain meaningful weight loss. The treatment also reduced major heart-related health issues, offering benefits beyond just weight loss. Overall, these findings provide strong evidence that semaglutide can effectively manage obesity. ^{6 7 8 9 10}

Who Is on the Research Team?

Katherine M Morrison, MD FRCPC

Principal Investigator

McMaster University

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40768192/

Real-World Weight Loss Among Patients Initiating ... The proportions of patients achieving ≥ 20% weight loss were 13.1%, 43.3%, 52.5%, and 50.5% at 6, 12, 18, and 24 months, respectively. Similar ...

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa2032183

Once-Weekly Semaglutide in Adults with Overweight or ... 2.4 mg of semaglutide once weekly plus lifestyle intervention was associated with sustained, clinically relevant reduction in body weight.

3. nature.com nature.com/articles/s41591-024-02996-7

Long-term weight loss effects of semaglutide in obesity ... In the SELECT cardiovascular outcomes trial, semaglutide showed a 20% reduction in major adverse cardiovascular events in 17,604 adults with ...

4. novomedlink.com novomedlink.com/obesity/products/treatments/wegovy/efficacy-safety/chronic-weight-management.html

Chronic Weight Management Trial Results | Wegovy ... Weight loss in pounds (lb) calculated as 5%, 10%, 15%, and 20% of mean baseline body weight of Wegovy® and placebo patients. Observed data include only ...

5. wegovy.com wegovy.com/about-wegovy/managing-weight-with-wegovy.html

Managing Weight with Wegovy 30% of adults (about 1 in 3) taking Wegovy® lost 20% or more weight compared with 2% of adults on placebo. This result was not the primary goal of the study and ...

6. novomedlink.com novomedlink.com/obesity/products/treatments/wegovy/efficacy-safety/safety-profile.html

Wegovy® Safety Profile A well-studied safety profile1. Safety data from three phase 3 weight-management clinical trials ... Once-weekly semaglutide in adults with overweight or obesity.

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2024/215256s011lbl.pdf

Wegovy (semaglutide) injection - accessdata.fda.gov WEGOVY 2.4 mg Subcutaneous Weekly Dosage WEGOVY was evaluated for safety in 3 randomized, double-blind, placebo-controlled trials that included 2,116 adult ...

8. nejm.org nejm.org/doi/full/10.1056/NEJMoa2307563

Semaglutide and Cardiovascular Outcomes in Obesity ... Adverse events leading to permanent discontinuation of the trial product occurred in 1461 patients (16.6%) in the semaglutide group and 718 patients (8.2%) in ...

9. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39948761/

Safety profile of semaglutide versus placebo in the ... The objective of this study was to assess safety of once-weekly subcutaneous semaglutide 2.4 mg versus placebo, beyond reduction in major adverse ...

10. nature.com nature.com/articles/s41591-022-02026-4

Two-year effects of semaglutide in adults with overweight ... In the 68-week trials, reductions in weight, waist circumference, blood pressure and HbA1c appeared to plateau around week 60 with semaglutide.