SMART Use of Medication for the Treatment of Adolescent Severe Obesity

NCT04007393 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: PEDS-2019-265121R01DK119456
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

This study will examine the timing and sequence of using adjunct obesity pharmacotherapy for adolescents with severe obesity who do not respond to lifestyle modification therapy alone.

Conditions

Adolescent Obesity

Outcome Measures

Primary Outcomes (1)

• Percent Change in Body Mass Index (BMI)

  The outcome values represent percent change in BMI from baseline to week 48.

  Baseline to Week 48

Study Arms (2)

LSMT 12

OTHER

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

Behavioral: Lifestyle Modification Therapy (LSMT); Drug: Phentermine Pill; Drug: Topiramate Pill; Drug: Placebo

LSMT 24

OTHER

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

Behavioral: Lifestyle Modification Therapy (LSMT); Drug: Phentermine Pill; Drug: Topiramate Pill; Drug: Placebo

Interventions

Lifestyle Modification Therapy (LSMT) BEHAVIORAL

LSMT will consist of both in-person and by telephone sessions delivered throughout the 48-week intervention phase. Each session will last 30-60 minutes. A trained study coordinator (a registered dietician or someone trained by our registered dietician) will deliver therapy which consists of counseling using education, goal setting and barrier reduction. Participants will be randomized to receive LSMT for 12 or 24 weeks before a re-assessment of their BMI.

LSMT 12; LSMT 24

Phentermine Pill DRUG

Phentermine will be started only if a participant does not lose 5% of BMI after 12 or 24 weeks of LSMT. Subjects will take 15 mg of phentermine every morning for 12 weeks at which time there will be an assessment of weight loss. Subjects who achieve 5% or more BMI reduction after 12 weeks of phentermine will continue 15 mg every morning for the remainder of the study (through week 48) along with their LSMT.

LSMT 12; LSMT 24

Topiramate Pill DRUG

Participants who do no not achieve at least 5% BMI reduction after 12 weeks of phentermine+LSMT will be re-randomized 1:1 to either topiramate+phentermine+LSMT or topiramate+placebo+LSMT. Topiramate dosing will begin at 50 mg every morning for the first 7 days, and then increase to 100 mg every morning through week 48. At the end of week 48 the taper off will be 50 mg every morning for 7 days and then discontinue.

LSMT 12; LSMT 24

Placebo DRUG

Participants who do no not achieve at least 5% BMI reduction after 12 weeks of phentermine+LSMT will be re-randomized 1:1 to either topiramate+phentermine+LSMT or topiramate+placebo+LSMT. Participants will take a placebo pill every morning.

LSMT 12; LSMT 24

Eligibility Criteria

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

You may qualify if:

• Provision of signed and dated informed assent form;
• Provision of signed and dated informed parental consent form from at least 1 legal parent/guardian;
• Stated willingness to comply with all study procedures and availability for the duration of the study;
• BMI \>/= 1.2 times the 95th percentile or BMI \>/= 35 Kg/m2, whichever is lower;
• Tanner stage \>/= 2;
• Male or female, aged 12-17 at time of consenting;
• For females of reproductive potential: when sexually active, agreement to use highly effective contraception (oral contraceptive pill, intra-uterine device (IUD), or implant) during study participation;
• For males of reproductive potential: use of condoms or other methods to ensure effective contraception with partner.

You may not qualify if:

• Contraindications to phentermine or topiramate use according to package inserts, including: history of glaucoma; current or recent (\< 14 days) use of monoamine oxidase inhibitor; known hypersensitivity to sympathomimetic amines; current pregnancy, plans to become pregnant, or if sexually active refusal to use 2 forms of birth control; history of cardiac disease including coronary artery disease; clinically significant cardiac arrhythmias; heart failure or uncontrolled hypertension;
• Diabetes (type 1 or 2);
• Presence of cardiac pacemaker;
• Current or recent (\<6 months prior to enrollment) use of weight loss medication(s);
• Current use of weight-altering medication(s) (e.g., atypical antipsychotic, metformin) unless dose has been stable for past 6 months;
• Current use of other sympathomimetic amine such as attention-deficit hyperactivity disorder (ADHD) stimulants;
• Seizure disorder (other than infantile febrile seizure);
• Previous bariatric surgery;
• Recent initiation of change in dose (\< 3 months prior to enrollment) of anti-hypertensive or lipid medication(s);
• Tobacco use
• History of or current diagnosis of schizophrenia, psychosis, mania, chemical dependency;
• Unstable depression or anxiety that has required hospitalization in the past year;
• Any history of suicide attempt;
• Suicidal ideation or self-harm within 12 months prior to enrollment;
• Bicarbonate \< 18 mmol/L;

Sponsors & Collaborators

• University of Minnesota: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

University of Minnesota

Minneapolis, Minnesota, 55414, United States

Location

MeSH Terms

Conditions

Pediatric Obesity

Interventions

Phentermine; Topiramate

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Amphetamines; Phenethylamines; Ethylamines; Amines; Organic Chemicals; Fructose; Hexoses; Monosaccharides; Sugars; Carbohydrates; Ketoses

Results Point of Contact

• Title: Claudia Fox
• Organization: University of Minnesota

lusc0001@umn.edu

612-626-6616

Study Officials

• Claudia Fox, MD, MPH

  University of Minnesota

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: At baseline, each participant will be randomized 1:1 to either the 12-week (Arm 1) or 24-week (Arm 2) response assessment to LSMT. This randomization will be blinded to the participant, investigator, and outcomes assessor for the duration of the study; i.e. up until 48 weeks. The second randomization includes only those participants who are non-responders to phentermine+LSMT. Each non-responder to phentermine+LSMT will be re-randomized 1:1 to either topiramate+phentermine+LSMT or topiramate+placebo+LSMT. Participants, investigators, and outcomes assessors will be blinded to phentermine/placebo. The topiramate will be open label.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 2-staged sequential multiple assignment randomized trial

Study Record Dates

• First Submitted: June 28, 2019
• First Posted: July 5, 2019
• Study Start: November 21, 2019
• Primary Completion: March 11, 2025
• Study Completion: March 11, 2025
• Last Updated: May 5, 2026
• Results First Posted: May 5, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

US (1)