Phentermine/Topiramate as Preventive Pharmacotherapy for Obesity

Sponsor

University of Minnesota (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05834062

Collaborator

(none)

140

Enrollment

Location

Arms

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study will test the use of phentermine and topiramate compared with placebo in helping adolescents who are at high risk for developing obesity to lose weight

Condition or Disease	Intervention/Treatment	Phase
Obesity, Adolescent	Drug: Qsymia and lifestyle management therapy Behavioral: Placebo and lifestyle management therapy	Phase 2

Detailed Description

This study will evaluate the effects of preventative pharmacotherapy on body mass index (BMI), as well as incidence of obesity and normal weight, in adolescents at high risk of developing obesity. We hypothesize that 24 months of Qsymia vs. placebo, in combination with lifestyle-based weight gain prevention coaching, will prevent increases in BMI (primary endpoint). More participants in the placebo group will develop obesity (cross the BMI 30 kg/m2 threshold) and more in the Qsymia group will transition to normal weight (drop below a BMI of 25 kg/m2).

All participants, regardless of medication/placebo assignment, will receive the same foundational weight gain prevention coaching throughout the entire study. The weight gain prevention coaching will be delivered individually by master's level behavioral intervention specialists with expertise in nutrition, physical activity, and weight-related behavior change. The multi-phase prevention intervention will start with 6 weekly 30-minute coaching calls followed by monthly 15-minute check-in calls for the remainder of the first year. At the beginning of the second year, a series of 3, 30-minute coaching calls will be held to revisit the information covered in the initial coaching calls, followed by bi-monthly 15-minute check-in calls for the remainder of the second year. The calls will be conducted via videoconference substituted with phone calls if needed.

The weight gain prevention intervention will utilize empirically supported behavior change strategies to help promote healthy dietary intake, physical activity patterns, and modest weight loss and/or prevent weight gain among participants. The intervention is informed by several of our previous weight loss and maintenance trials and the work of others, including weight gain prevention trials in young adult populations. The core prevention intervention is based on a behavioral conceptualization of effective weight management that emphasizes: 1) identifying behaviors in need of change; 2) setting goals for change; 3) monitoring progress; 4) modifying environmental cues to facilitate change; and 5) modifying consequences to motivate change. The intervention will incorporate core behavior change strategies including self-monitoring, stimulus control, modeling, goal setting, and positive reinforcement, which were among the common behavior change elements identified across the 17 treatment arms used in the Early Adult Reduction of weight through LifestYle (EARLY) weight management trials that included the young adult weight gain prevention trials previously referenced.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

140 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

This is a randomized, double-blind, placebo-controlled clinical trialThis is a randomized, double-blind, placebo-controlled clinical trial

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Phentermine/Topiramate as Preventive Pharmacotherapy for Obesity

Anticipated Study Start Date :

Sep 1, 2023

Anticipated Primary Completion Date :

Aug 1, 2026

Anticipated Study Completion Date :

Aug 1, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Medication arm Individuals randomized to this group will be offered lifestyle-based weight gain prevention counseling. Participants will initiate treatment at 3.75 mg/23 mg orally once in the morning for 14 days, which will then be increased to 7.5 mg/46 mg orally once daily in the morning for the remainder of the trial. Participants who are unable to tolerate the dosing regimen will be maintained at the maximally tolerated dose. To further safeguard the risk/benefit balance we will utilize a down-titration protocol for participants who experience a reduction in BMI below a threshold of 20 kg/m2. In this case, participants will be reduced to the lowest-dose level (3.75 mg/23 mg) for 12 weeks. If the BMI remains below 20 kg/m2 at the lowest dose after 12 weeks, active treatment will be fully withdrawn. Participants at the end of the study will be down-titrated gradually with instructions to take the medication every other day for 7 days before stopping treatment altogether.	Drug: Qsymia and lifestyle management therapy Qsymia will be used at 3.7g mg/23 mg for 12 weeks and then increased to 7.5 mg/46 mg for the remainder of the study. Participants will be offered lifestyle management therapy.
Placebo Comparator: Placebo arm Individuals randomized to this group will be offered lifestyle-based weight gain prevention counseling. Participants will initiate treatment with a placebo (to keep the blind) and be asked to up-titrate the placebo dose after the first 14 days and then maintain the placebo dose for the remainder of the study. Individuals who are unable to tolerate the dosing regimen will have a down-titration protocol (to maintain the blind) as described in the medication arm. Likewise, we will employ a down-titration protocol for participants who experience a reduction in BMI below a threshold of 20 kg/m2. In this case, participants would be reduced to the lowest dose level of placebo for 12 weeks. If the BMI remains below 20 kg/m2 after 12 weeks, placebo treatment will be fully withdrawn. Individuals in the placebo arm will also have a placebo-based down-titration with instructions to take the placebo every other day for 7 days before stopping treatment altogether, to maintain the blind.	Behavioral: Placebo and lifestyle management therapy Placebo will be used in lieu of Qsymia to maintain the blind. Participants will be offered lifestyle management therapy.

Arm

Intervention/Treatment

Experimental: Medication arm

Individuals randomized to this group will be offered lifestyle-based weight gain prevention counseling. Participants will initiate treatment at 3.75 mg/23 mg orally once in the morning for 14 days, which will then be increased to 7.5 mg/46 mg orally once daily in the morning for the remainder of the trial. Participants who are unable to tolerate the dosing regimen will be maintained at the maximally tolerated dose. To further safeguard the risk/benefit balance we will utilize a down-titration protocol for participants who experience a reduction in BMI below a threshold of 20 kg/m2. In this case, participants will be reduced to the lowest-dose level (3.75 mg/23 mg) for 12 weeks. If the BMI remains below 20 kg/m2 at the lowest dose after 12 weeks, active treatment will be fully withdrawn. Participants at the end of the study will be down-titrated gradually with instructions to take the medication every other day for 7 days before stopping treatment altogether.

Drug: Qsymia and lifestyle management therapy

Qsymia will be used at 3.7g mg/23 mg for 12 weeks and then increased to 7.5 mg/46 mg for the remainder of the study. Participants will be offered lifestyle management therapy.

Placebo Comparator: Placebo arm

Individuals randomized to this group will be offered lifestyle-based weight gain prevention counseling. Participants will initiate treatment with a placebo (to keep the blind) and be asked to up-titrate the placebo dose after the first 14 days and then maintain the placebo dose for the remainder of the study. Individuals who are unable to tolerate the dosing regimen will have a down-titration protocol (to maintain the blind) as described in the medication arm. Likewise, we will employ a down-titration protocol for participants who experience a reduction in BMI below a threshold of 20 kg/m2. In this case, participants would be reduced to the lowest dose level of placebo for 12 weeks. If the BMI remains below 20 kg/m2 after 12 weeks, placebo treatment will be fully withdrawn. Individuals in the placebo arm will also have a placebo-based down-titration with instructions to take the placebo every other day for 7 days before stopping treatment altogether, to maintain the blind.

Behavioral: Placebo and lifestyle management therapy

Placebo will be used in lieu of Qsymia to maintain the blind. Participants will be offered lifestyle management therapy.

Outcome Measures

Primary Outcome Measures

Evaluate effects of preventive pharmacotherapy and lifestyle-based weight gain prevention on body mass index between the medication arm and the placebo arm [24 months]
Change in BMI

Eligibility Criteria

Criteria

Ages Eligible for Study:

16 Years to 22 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Age 16 to less than 22 years at screening
BMI >/= 25 to < 30 kg/m^2
Family history of obesity defined as one biological parent with severe obesity (BMI

/= 35) and/or two biological parents with obesity (BMI >/= 30)

Age 16 or 17 years old must also have an obesity-related complication/co-morbidity defined as elevated blood pressure (>/= 130 and/or >/= 80 milligrams of mercury [mmHg]) or current use of anti-hypertensive medication, dyslipidemia (triglycerides

/= 150 milligrams/deciliter (mg/dL) and/or HDL cholesterol < 40 mg/dL or current use of cholesterol-lowering medication, diagnosis of obstructive sleep apnea

Exclusion Criteria:

Tanner stage 1-4
Diabetes (1 or 2)
Current or recent (< 6 months prior to enrollment) use of anti-obesity medication(s) and other weight-altering medication(s) (e.g.,, atypical antipsychotics, attention-deficit hyperactivity disorder [ADHD] stimulant)
Previous bariatric surgery
Current or recent (< 6 months prior to enrollment) use of medication(s) to treat insulin resistance
Recent initiation (< 3 months prior to enrollment) of anti-hypertensive or lipid medication(s)
History of glaucoma
Current or recent (< 14 days) use of monoamine oxidase inhibitor
Known hypersensitivity to sympathomimetic amines
History of treatment with growth hormone
Patient Health Questionnaire (PHQ) score of >/= 15
Eating disorder symptoms within 6 months and/r any past medical diagnosis of eating disorder
Major psychiatric disorder
Unstable clinically-diagnosed depression
History of suicide attempt
Suicidal ideation of type 4 or 5 on the Columbia-Suicide Severity Rating Scale (C-SSRS) in the last month
Current pregnancy or breastfeeding
Plans to become pregnant
If sexually active, refusal to use 2 forms of birth control
Tobacco use
Alanine transaminase (ALT ) or Aspartate transaminase (AST) >/= 2.5 the upper limit of normal
Bicarbonate < 18 micromoles per liter (mmol/L)
Creatinine 1.2 mg/dL
Creatinine clearance of < 50 microliters per minute [mL/min] (Schwartz formula)
History of seizures
Uncontrolled hypertension
History of structural heart defect
History of clinically significant arrhythmia
Diagnosed monogenic obesity
History of cholelithiasis
History of nephrolithiasis
Hyperthyroidism
Untreated thyroid disorder

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Minnesota	Minneapolis	Minnesota	United States	55414

Sponsors and Collaborators

University of Minnesota

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

University of Minnesota

ClinicalTrials.gov Identifier:

NCT05834062

Other Study ID Numbers:

PEDS-2022-31025

First Posted:

Apr 28, 2023

Last Update Posted:

Apr 28, 2023

Last Verified:

Apr 1, 2023

Individual Participant Data (IPD) Sharing Statement:

Undecided

Plan to Share IPD:

Undecided

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Obesity

Pediatric Obesity

Study Results

No Results Posted as of Apr 28, 2023