Medication + Lifestyle Changes for Adolescent Severe Obesity

(SMART Trial)

Overseen By Claudia Fox, MD, MPH

Age: < 18

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Minnesota

Must not be taking: Weight loss drugs, ADHD stimulants

Disqualifiers: Diabetes, Cardiac disease, Schizophrenia, others

Stay on Your Current Meds You can continue your current medications while participating

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 tests a combination of medication and lifestyle changes to assist adolescents with severe obesity who haven't achieved sufficient weight loss through lifestyle changes alone. It examines the timing and sequence of adding medications like phentermine and topiramate to determine if they enhance weight loss when lifestyle changes fall short. The trial targets teens aged 12-17 who have struggled with severe obesity, defined as a weight significantly higher than average for their age and height. Researchers will monitor participants to assess how different treatments impact their weight over time. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to significant findings.

Will I have to stop taking my current medications?

The trial requires that you stop using weight loss medications if you've used them in the last 6 months and weight-altering medications unless the dose has been stable for the past 6 months. If you're taking ADHD stimulants or have recently changed your dose of anti-hypertensive or lipid medications, you may also need to stop or stabilize these before joining.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies have shown promising safety results for using phentermine and topiramate to treat obesity in teenagers. Phentermine, often combined with lifestyle changes, has been reported to help reduce body weight over time. Monitoring heart rate is important when taking phentermine, as it may affect it.

Topiramate also appears safe when used with lifestyle changes. Research indicates that topiramate can effectively aid in weight reduction while remaining safe. The combination of phentermine and topiramate is generally well-tolerated in teenagers, with most experiencing positive weight management results.

Both medications have been safely tested in teenagers for up to 12 weeks. Although both treatments are generally safe, regular check-ups are crucial to ensure participants respond well. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of phentermine and topiramate with lifestyle changes for adolescent severe obesity because it offers a multi-faceted approach that could enhance weight loss outcomes. Phentermine is a well-known appetite suppressant, and topiramate is believed to impact weight by affecting certain brain pathways. This combination, alongside lifestyle and behavioral changes, targets both physiological and behavioral factors contributing to obesity. Unlike treatments that focus solely on lifestyle modifications or medication, this approach could offer a more comprehensive solution, potentially leading to more significant and sustained weight loss in adolescents.

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

Studies have shown that phentermine, one of the medications tested in this trial, can help lower body mass index (BMI) in teenagers with obesity. For example, real-world evidence indicates that phentermine decreased BMI for most patients over 3 to 12 months. Research also shows that topiramate, another medication under study, combined with lifestyle changes, resulted in a significant BMI reduction of about 4–6% in teenagers. Additionally, using both phentermine and topiramate together has demonstrated significant weight loss benefits, with some studies in adults reporting a 9.8% to 11.0% weight loss over a year. These findings suggest that both medications can effectively support weight loss in teenagers dealing with severe obesity. ^{1 2 3 4 5}

Who Is on the Research Team?

Claudia Fox, MD

Principal Investigator

University of Minnesota

Are You a Good Fit for This Trial?

This trial is for teens aged 12-17 with severe obesity who haven't improved with lifestyle changes alone. They must be willing to use effective contraception if sexually active, and commit to the study's duration. Exclusions include diabetes, heart conditions, certain mental health issues, untreated thyroid disorders, previous weight loss surgery or medication use.

Inclusion Criteria

My BMI is at or above the lower of 1.2 times the 95th percentile or 35 Kg/m2.

Provision of signed and dated informed assent form

I am between 12 and 17 years old.

Exclusion Criteria

I have a thyroid condition that hasn't been treated.

You smoke or use tobacco products.

I have a seizure disorder, not just childhood febrile seizures.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lifestyle Modification Therapy (LSMT)

Participants start with a lifestyle modification program to assess initial weight loss response

12-24 weeks

Regular visits for weight assessment

Pharmacotherapy Addition

Participants who do not achieve a 5% BMI reduction add phentermine to LSMT

12 weeks

Regular visits for weight assessment and medication adjustment

Advanced Pharmacotherapy

Participants who do not achieve a 5% BMI reduction with phentermine are randomized to additional medication regimens

12-24 weeks

Regular visits for weight assessment and medication adjustment

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Phentermine Pill
• Topiramate Pill

Trial Overview The study tests how well adding obesity drugs Phentermine and Topiramate works after lifestyle modification therapy in adolescents. It looks at the best timing and sequence for introducing these medications when lifestyle changes aren't enough.

How Is the Trial Designed?

Group I: LSMT x 24 weeks Experimental Treatment 3 Interventions

Participants in this arm will start LSMT at baseline and have a weight loss response assessment at T=24 weeks: if body mass index (BMI) is down 5% at T=24 weeks, the participant will continue with LSMT for the remainder of the study (i.e. for another 24 weeks); if BMI is not down 5% at T=24 weeks, the participant will add phentermine to LSMT (phentermine+LSMT) and undergo a second weight loss response assessment after 12 weeks of phentermine+LSMT; i.e. at T=36 weeks. At T=36 weeks, if BMI is down 5% with phentermine+LSMT, the participant will continue with phentermine+LSMT for the the remainder of study (i.e. for another 12 weeks); if BMI is not down by 5% at T=36 weeks, the participant will be randomized to topiramate+phentermine+LSMT or topiramate+placebo+LSMT for the remainder of the study (i.e. for another 12 weeks).

Group II: LSMT x 12 weeks Experimental Treatment 3 Interventions

Participants in this arm will start LSMT at baseline and have a weight loss response assessment at T=12 weeks: if body mass index (BMI) is down 5% at T=12 weeks, the participant will continue with LSMT for the remainder of the study (i.e. for another 36 weeks); if BMI is not down 5% at T=12 weeks, the participant will add phentermine to LSMT (phentermine+LSMT) and undergo a second weight loss response assessment after 12 weeks of phentermine+LSMT; i.e. at T=24 weeks. At T=24 weeks, if BMI is down 5% with phentermine+LSMT, the participant will continue with phentermine+LSMT for the the remainder of study (i.e. for another 24 weeks); if BMI is not down by 5% at T=24 weeks, the participant will be randomized to topiramate+phentermine+LSMT or topiramate+placebo+LSMT for the remainder of the study (i.e. for another 24 weeks).

Who Is Running the Clinical Trial?

University of Minnesota

Lead Sponsor

Trials

1,459

Recruited

1,623,000+

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Collaborator

Trials

2,513

Recruited

4,366,000+

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40600300/

Real-World Use of Phentermine and Topiramate for ... Conclusions: Phentermine and/or topiramate resulted in BMI reduction in most patients exposed for 3-12 months. Safety data support ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10698794/

Real-World Experience of the Efficacy and Safety of ... Data gathered from the Lorber trials established safe to use in children and adolescents, from 3 to 15 years old, for 12 weeks. Our data further support its ...

3. cdc.gov cdc.gov/mmwr/volumes/74/wr/mm7420a1.htm

Prescriptions for Obesity Medications Among Adolescents ... This report describes the proportion of adolescents with obesity who were prescribed an obesity medication during 2018–2023.

4. liebertpub.com liebertpub.com/doi/full/10.1089/chi.2025.0007?doi=10.1089/chi.2025.0007

Real-World Use of Phentermine and Topiramate for ... Conclusions: Phentermine and/or topiramate resulted in BMI reduction in most patients exposed for 3–12 months. Safety data support ...

5. evidence.nejm.org evidence.nejm.org/doi/full/10.1056/EVIDoa2200014

Phentermine/Topiramate for the Treatment of Adolescent ... A mean placebo-subtracted weight loss of 9.8% to 11.0% was achieved after 1 year of treatment in adults with obesity randomly assigned to top- ...