PROJECT-BARI: Pharmacotherapy in Conjunction With Lifestyle Counseling for Management of Weight Regain After Bariatric Surgery

Sponsor

University of California, Irvine (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05975580

Collaborator

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

120

Enrollment

Location

Arms

47.7

Anticipated Duration (Months)

2.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a randomized controlled trial employing a Sequential Multiple Assignment Randomized Trial (SMART) design to test whether pharmacotherapy, in conjunction with lifestyle counseling, can reverse weight regain after bariatric surgery.

Condition or Disease	Intervention/Treatment	Phase
Obesity	Drug: Topiramate Drug: Phentermine Drug: Placebo	Phase 4

Detailed Description

Although bariatric surgery is the most effective treatment for severe obesity, a large proportion of patients experience significant weight regain with longer follow-up.

In this randomized controlled trial employing a SMART design, a total of 120 subjects with weight regain after bariatric surgery, will be initially randomized in a 3:3:2 ratio to daily treatment with topiramate (TPM) 50 mg or phentermine (PHEN) 7.5 mg or placebo. After 4 months, responders (those with ≥5% weight loss) will continue the same treatment, while nonresponders will be re-randomized to a higher dose of the same drug or phentermine/topiramate 7.5/50 mg combination (PHEN/TPM) during Months 5-12. All subjects will receive diet and lifestyle counseling throughout the study.

Aim 1: To determine whether pharmacotherapy can reverse post-bariatric surgery weight regain.

Hypothesis: Compared to placebo, all three active drug therapies - TPM, PHEN, and PHEN/TPM will lead to greater percent weight loss at Month 12.

Aim 2: To examine change in energy intake assessed by a dietitian interview.

Hypothesis: Compared to placebo, active drug therapies will lead to greater reduction in energy intake at Month 12.

Aim 3: To examine changes in the most common maladaptive eating behaviors in the post-bariatric surgery patients - grazing, loss-of-control eating, and binge eating.

Hypothesis: Compared to placebo, active drug therapies will lead to decreased maladaptive eating behaviors.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

120 participants

Allocation:

Randomized

Intervention Model:

Sequential Assignment

Intervention Model Description:

A total of 120 eligible subjects, with weight regain after bariatric surgery, will be initially randomized in a 3:3:2 ratio to daily treatment with topiramate (TPM) 50 mg or phentermine (PHEN) 7.5 mg or placebo. After 4 months, responders (those with ≥5% weight loss) will continue the same treatment, while nonresponders will be re-randomized to a higher dose of the same drug or phentermine/topiramate 7.5/50 mg combination (PHEN/TPM) during Months 5-12. All randomized subjects will receive lifestyle counseling throughout the study.A total of 120 eligible subjects, with weight regain after bariatric surgery, will be initially randomized in a 3:3:2 ratio to daily treatment with topiramate (TPM) 50 mg or phentermine (PHEN) 7.5 mg or placebo. After 4 months, responders (those with ≥5% weight loss) will continue the same treatment, while nonresponders will be re-randomized to a higher dose of the same drug or phentermine/topiramate 7.5/50 mg combination (PHEN/TPM) during Months 5-12. All randomized subjects will receive lifestyle counseling throughout the study.

Masking:

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

Masking Description:

The investigational drugs and placebo capsules will look identical. University of California Irvine Medical Center Investigational Drug Service will dispense the masked study drugs in accordance with randomization. The study statistician who generates the randomization scheme and the research pharmacist who dispenses the study drugs are the only personnel who are unblinded to the randomized assignment. Investigators and all other study personnel and the study subjects will be blinded to the treatment assignment until subjects have completed all visits, all data have been entered, and the data file has been locked.

Primary Purpose:

Treatment

Official Title:

Pharmacotherapy in Conjunction With Lifestyle Counseling for Management of Weight Regain After Bariatric Surgery

Anticipated Study Start Date :

Aug 10, 2023

Anticipated Primary Completion Date :

Apr 2, 2027

Anticipated Study Completion Date :

Jul 31, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Group A: Topiramate 50 mg Topiramate will be started at 25 mg daily and the dose will be increased to 50 mg daily after 15 days. Responders at Month 4 will continue the same treatment until Month 12.	Drug: Topiramate Topiramate is an anticonvulsant (antiepilepsy) drug. IUPAC ID: 2,3:4,5-Bis-O-(1-methylethylidene)-beta-D-fructopyranose sulfamate
Experimental: Group B: Topiramate 100 mg Nonresponders in the topiramate group at Month 4 will be re-randomized in a 1:1 ratio to receive topiramate 100 mg or phentermine/topiramate 7.5/50 mg during Months 5-12.	Drug: Topiramate Topiramate is an anticonvulsant (antiepilepsy) drug. IUPAC ID: 2,3:4,5-Bis-O-(1-methylethylidene)-beta-D-fructopyranose sulfamate
Experimental: Group C: Phentermine 7.5 mg/Topiramate 50 mg Nonresponders in the topiramate group at Month 4 will be re-randomized in a 1:1 ratio to receive topiramate 100 mg or phentermine/topiramate 7.5/50 mg during Months 5-12.	Drug: Topiramate Topiramate is an anticonvulsant (antiepilepsy) drug. IUPAC ID: 2,3:4,5-Bis-O-(1-methylethylidene)-beta-D-fructopyranose sulfamate Drug: Phentermine Phentermine belongs to a class of drugs called anorectics, also known as appetite suppressants. IUPAC name 2-methyl-1-phenylpropan-2-amine
Experimental: Group D: Phentermine 7.5 mg Phentermine will be started at 7.5 mg daily. Responders at Month 4 will continue the same treatment until Month 12.	Drug: Phentermine Phentermine belongs to a class of drugs called anorectics, also known as appetite suppressants. IUPAC name 2-methyl-1-phenylpropan-2-amine
Experimental: Group E: Phentermine 15 mg Nonresponders in the phentermine group at Month 4 will be re-randomized in a 1:1 ratio to receive phentermine 15 mg or phentermine/topiramate 7.5/50 mg during Months 5-12.	Drug: Phentermine Phentermine belongs to a class of drugs called anorectics, also known as appetite suppressants. IUPAC name 2-methyl-1-phenylpropan-2-amine
Experimental: Group F: Phentermine 7.5 mg/Topiramate 50 mg Nonresponders in the phentermine group at Month 4 will be re-randomized in a 1:1 ratio to receive phentermine 15 mg or phentermine/topiramate 7.5/50 mg during Months 5-12. For Group F, topiramate will be dosed at 25 mg daily for the 15 days in Month 5 and 50 mg daily thereafter,	Drug: Topiramate Topiramate is an anticonvulsant (antiepilepsy) drug. IUPAC ID: 2,3:4,5-Bis-O-(1-methylethylidene)-beta-D-fructopyranose sulfamate Drug: Phentermine Phentermine belongs to a class of drugs called anorectics, also known as appetite suppressants. IUPAC name 2-methyl-1-phenylpropan-2-amine
Placebo Comparator: Group P: Placebo Placebo group will receive placebo.	Drug: Placebo Placebo is an inactive substance.

Outcome Measures

Primary Outcome Measures

Percent weight loss at Month 12 - Topiramate vs placebo [Month 0, Month 12]
Topiramate (Group 1 [Group A + Group B]) vs placebo (Group P)
Percent weight loss at Month 12 - Phentermine vs placebo [Month 0, Month 12]
Phentermine (Group 2 [Group D + Group E) vs placebo (Group P)
Percent weight loss at Month 12 - Phentermine/Topiramate [Month 0, Month 12]
Phentermine/Topiramate (Group 3 [Group C + Group F]) vs placebo (Group P)

Secondary Outcome Measures

Energy intake [Month 0, Month 12]
Change in energy intake in kcal/d assessed with a dietitian interview. Comparisons between Groups 1, 2, 3 vs placebo.

Other Outcome Measures

Grazing [Months 0, 4, 12]
Change in grazing behavior, assessed with the Grazing Questionnaire. Comparisons between Groups 1, 2, 3 vs placebo.
Loss-of-control eating [Months 0, 4, 12]
Change in loss-of-control eating, assessed with the Loss-of-Control Eating Scale. Comparisons between Groups 1, 2, 3 vs placebo.
Binge eating [Months 0, 4, 12]
Change in binge eating, assessed with the Binge Eating Scale. Comparisons between Groups 1, 2, 3 vs placebo.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Male and female subjects aged 18-70 years
Had sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB) between ≥18 months and ≤10 years ago
Weight regain of ≥5% relative to post-surgery nadir weight
Body mass index (BMI) ≥30 kg/m2 or ≥27 kg/m2 with weight-related comorbidities
Women of childbearing potential must be using appropriate contraception to avoid pregnancy throughout the study, and must have a negative pregnancy test at study entry
Must be able to provide written informed consent

Exclusion Criteria:

Type 1 diabetes
Insulin-dependent type 2 diabetes
Fasting plasma glucose (FPG) ≥240 mg/dL
Uncontrolled hypertension defined as systolic blood pressure (SBP) ≥150 mm Hg and/or diastolic blood pressure (DBP) ≥100 mm Hg on the average of three seated measurements after being at rest for at least 5 minutes
History of significant (as determined by the investigator) and unstable cardiovascular disease including coronary artery disease, arrhythmias, severe congestive heart failure, or stroke
Use of monoamine oxidase inhibitors, current or within 2 weeks
Hyperthyroidism or other significant thyroid disease
Angle-closure glaucoma
Agitated states
History of drug abuse within the past year
Known hypersensitivity or idiosyncrasy to sympathomimetic amines
Severe hepatic disease (non-alcoholic fatty liver disease or non-alcoholic steatohepatitis without portal hypertension or cirrhosis is acceptable)
End-stage renal disease
History of nephrolithiasis
Serum triglycerides ≥500 mg/dL
Cancer, not in remission, within the past 2 years except for adequately treated basal cell, squamous cell skin cancer, or in-situ cervical cancer
History of psychosis or bipolar disorder
Suicidal ideation or unstable/untreated major depressive disorder within the past year
Use of antidepressant medication that has not been at stable dose for at least 3 months
Hospital Anxiety and Depression Scale (HADS) score of ≥11 for depression or anxiety items
Binge Eating Scale (BES) score of ≥27
Alcohol use disorder within the past year
Epilepsy
Currently taking phentermine or topiramate or the combination, or products containing these drugs
Currently taking stimulants (e.g., Attention Deficit Hyperactivity Disorder medications)
Current use of prescription or over-the-counter weight loss drugs or supplements
Taking prescription or over-the-counter drugs or products, which in the opinion of the PI, could be associated with significant effects on body weight
Planning additional bariatric surgery procedures in the next 13 months
History of revisional bariatric surgery (revisional surgery after adjustable gastric banding is acceptable)
Currently participating in another weight loss program or have plans to participate in the next 13 months
Smoking cessation within the previous 3 months or plans to quit smoking in the next 13 months
Pregnant or breastfeeding or planning pregnancy in the coming 13 months
History of, or any existing condition that, in the opinion of the Principal Investigator, would interfere with the study outcomes or place the subject at unacceptable risk by participating in the study