SMART Use of Medication for the Treatment of Adolescent Severe Obesity (SMART)

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ClinicalTrials.gov Identifier: NCT04007393

Recruitment Status : Recruiting

First Posted : July 5, 2019

Last Update Posted : September 26, 2022

See Contacts and Locations

View this study on Beta.ClinicalTrials.gov

Sponsor:

Collaborator:

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

Information provided by (Responsible Party):

University of Minnesota

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Adolescent Obesity	Behavioral: Lifestyle Modification Therapy (LSMT) Drug: Phentermine Pill Drug: Topiramate Pill	Phase 2

Detailed Description:

This project is studying the best time to add weight loss medication to diet and exercise for helping adolescents who carry extra weight. All participants start with a lifestyle modification program and some participants may also receive study medication.Participants must be 12-17 years of age and carry extra weight. The program will last for 48 weeks.

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	150 participants
Allocation:	Randomized
Intervention Model:	Sequential Assignment
Intervention Model Description:	2-staged sequential multiple assignment randomized trial
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:	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.
Primary Purpose:	Treatment
Official Title:	SMART Use of Medication for the Treatment of Adolescent Severe Obesity
Actual Study Start Date :	November 21, 2019
Estimated Primary Completion Date :	August 31, 2024
Estimated Study Completion Date :	August 31, 2025

Resource links provided by the National Library of Medicine

Drug Information available for: Phentermine Phentermine hydrochloride Topiramate

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
LSMT x 12 weeks 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).	Behavioral: Lifestyle Modification Therapy (LSMT) LSMT will consist of both in-person and by telephone sessions delivered throughout the entirety of 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 delivery this therapy which consists of counseling using education, goal setting and barrier reduction. Topics covered will include calories, tracking, healthy food choices, reducing high fat, added sugar foods, setting goals and portions, changing the quality of your diet, volumetrics, purposeful activity, quick and easy meals, problem solving, food cues and eating patterns, emotional eating, accurate tracking, eating away from home, unhelpful thoughts, structured menus and the role of protein, social cues, managing stress, slips and relapse prevention, long-term physical activity and overcoming obstacles, high-risk situation and keys to success, motivation and looking to the future (long-term plans). Drug: Phentermine Pill Phentermine will be started only if a participant does not lose 5% of BMI after 12 or 24 weeks of LSMT depending on their random assignment. 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. Drug: Topiramate Pill 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 x 24 weeks 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).	Behavioral: Lifestyle Modification Therapy (LSMT) LSMT will consist of both in-person and by telephone sessions delivered throughout the entirety of 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 delivery this therapy which consists of counseling using education, goal setting and barrier reduction. Topics covered will include calories, tracking, healthy food choices, reducing high fat, added sugar foods, setting goals and portions, changing the quality of your diet, volumetrics, purposeful activity, quick and easy meals, problem solving, food cues and eating patterns, emotional eating, accurate tracking, eating away from home, unhelpful thoughts, structured menus and the role of protein, social cues, managing stress, slips and relapse prevention, long-term physical activity and overcoming obstacles, high-risk situation and keys to success, motivation and looking to the future (long-term plans). Drug: Phentermine Pill Phentermine will be started only if a participant does not lose 5% of BMI after 12 or 24 weeks of LSMT depending on their random assignment. 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. Drug: Topiramate Pill 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.

Arm

Intervention/treatment

LSMT x 12 weeks

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).

Behavioral: Lifestyle Modification Therapy (LSMT)

LSMT will consist of both in-person and by telephone sessions delivered throughout the entirety of 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 delivery this therapy which consists of counseling using education, goal setting and barrier reduction. Topics covered will include calories, tracking, healthy food choices, reducing high fat, added sugar foods, setting goals and portions, changing the quality of your diet, volumetrics, purposeful activity, quick and easy meals, problem solving, food cues and eating patterns, emotional eating, accurate tracking, eating away from home, unhelpful thoughts, structured menus and the role of protein, social cues, managing stress, slips and relapse prevention, long-term physical activity and overcoming obstacles, high-risk situation and keys to success, motivation and looking to the future (long-term plans).

Drug: Phentermine Pill

Phentermine will be started only if a participant does not lose 5% of BMI after 12 or 24 weeks of LSMT depending on their random assignment. 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.

Drug: Topiramate Pill

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 x 24 weeks

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).

Behavioral: Lifestyle Modification Therapy (LSMT)

Drug: Phentermine Pill

Drug: Topiramate Pill

Outcome Measures

Primary Outcome Measures :

Percent change in body mass index (BMI) [ Time Frame: Baseline, 12-, 24-, 36-, and 48 weeks ]
Body mass index is a measure of body fat based on height and weight.

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:	12 Years to 17 Years (Child)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

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.

Exclusion Criteria:

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;
Creatinine > 1.2 mg/dL;
History of cholelithiasis;
History of nephrolithiasis;
Untreated thyroid disorder;
Hyperthyroidism;
Breastfeeding

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04007393

Contacts

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Contact: Claudia Fox, MD, MPH	(612)626-6616	lusc0001@umn.edu

Locations

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United States, Minnesota
University of Minnesota	Recruiting
Minneapolis, Minnesota, United States, 55414
Contact: Claudia Fox, MD 612-626-6616 lusc0001@umn.edu
Contact: Nina Jacobs (612)624-3137 njacobs@umn.edu

Sponsors and Collaborators

University of Minnesota

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

Investigators

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Principal Investigator:	Claudia Fox, MD, MPH	University of Minnesota

More Information

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Responsible Party:	University of Minnesota
ClinicalTrials.gov Identifier:	NCT04007393
Other Study ID Numbers:	PEDS-2019-26512 1R01DK119456 ( U.S. NIH Grant/Contract )
First Posted:	July 5, 2019 Key Record Dates
Last Update Posted:	September 26, 2022
Last Verified:	September 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	Undecided

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Studies a U.S. FDA-regulated Drug Product:	Yes
Studies a U.S. FDA-regulated Device Product:	No

Additional relevant MeSH terms:

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Obesity Obesity, Morbid Pediatric Obesity Overweight Overnutrition Nutrition Disorders Body Weight Topiramate Phentermine Anticonvulsants Hypoglycemic Agents	Physiological Effects of Drugs Central Nervous System Stimulants Appetite Depressants Anti-Obesity Agents Sympathomimetics Autonomic Agents Peripheral Nervous System Agents Adrenergic Agents Neurotransmitter Agents Molecular Mechanisms of Pharmacological Action

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