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

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ClinicalTrials.gov Identifier: NCT04007393
Recruitment Status : Not yet recruiting
First Posted : July 3, 2019
Last Update Posted : July 12, 2019
Sponsor:
Collaborator:
National Institutes of Health (NIH)
Information provided by (Responsible Party):
University of Minnesota - Clinical and Translational Science Institute

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 is a single site, 2-staged sequential multiple assignment randomized trial (SMART) that will systematically examine: 1) the optimal timing (12- versus 24 weeks) for identifying non-responders to lifestyle modification therapy (LSMT) before starting adjunct pharmacotherapy with phentermine and 2) for non-responders to phentermine+LSMT, the relative effect of adding topiramate to phentermine+LSMT versus switching to topiramate monotherapy+LSMT. All participants will receive a total of 48 weeks of intervention. Participant characteristics that differentially predict outcomes and mechanisms that may account for the relative effects will also be examined.

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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
Estimated Study Start Date : September 2019
Estimated Primary Completion Date : August 2024
Estimated Study Completion Date : August 2025

Resource links provided by the National Library of Medicine


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.




Primary Outcome Measures :
  1. 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.



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

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

Sponsors and Collaborators
University of Minnesota - Clinical and Translational Science Institute
National Institutes of Health (NIH)
Investigators
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Principal Investigator: Claudia Fox, MD, MPH University of Minnesota - Clinical and Translational Science Institute

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Responsible Party: University of Minnesota - Clinical and Translational Science Institute
ClinicalTrials.gov Identifier: NCT04007393     History of Changes
Other Study ID Numbers: STUDY00006824
First Posted: July 3, 2019    Key Record Dates
Last Update Posted: July 12, 2019
Last Verified: July 2019
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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Nutrition Disorders
Obesity
Obesity, Morbid
Pediatric Obesity
Overnutrition
Overweight
Body Weight
Signs and Symptoms
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