Clinical trial NCT05975580: Pharmacotherapy in Conjunction With Lifestyle Counseling for Management of Weight Regain After Bariatric Surgery
Official title: Pharmacotherapy in Conjunction With Lifestyle Counseling for Management of Weight Regain After Bariatric Surgery
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Obesity
Keywords: Bariatric surgery
Weight regain
Antiobesity drugs
Treatment of weight regain
Lead sponsor: University of California, Irvine
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2023-08-04
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
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) or phentermine (PHEN) 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 combination (PHEN/TPM) during Months 5-12. All randomized subjects will receive lifestyle counseling throughout the study.
Primary purpose: TREATMENT

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.

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) or phentermine (PHEN) 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 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.

Eligibility criteria: Inclusion Criteria:

1. Male and female subjects aged 18-70 years
2. Had sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB) at least 18 months ago
3. Weight regain of ≥5% relative to post-surgery nadir weight
4. Body mass index (BMI) ≥30 kg/m2 or ≥27 kg/m2 with weight-related comorbidities
5. 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
6. Must be able to provide written informed consent

Exclusion Criteria:

1. Type 1 diabetes
2. Insulin-dependent type 2 diabetes
3. Fasting plasma glucose (FPG) ≥240 mg/dL
4. 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
5. History of significant (as determined by the investigator) and unstable cardiovascular disease including coronary artery disease, arrhythmias, severe congestive heart failure, or stroke
6. Use of monoamine oxidase inhibitors, current or within 2 weeks
7. Hyperthyroidism or other significant thyroid disease
8. Angle-closure glaucoma
9. Agitated states
10. History of drug abuse within the past year
11. Known hypersensitivity or idiosyncrasy to sympathomimetic amines
12. Severe hepatic disease (non-alcoholic fatty liver disease or non-alcoholic steatohepatitis without portal hypertension or cirrhosis is acceptable)
13. End-stage renal disease
14. History of nephrolithiasis
15. Serum triglycerides ≥500 mg/dL
16. Cancer, not in remission, within the past 2 years except for adequately treated basal cell, squamous cell skin cancer, or in-situ cervical cancer
17. History of psychosis or bipolar disorder
18. Suicidal ideation or unstable/untreated major depressive disorder within the past year
19. Use of antidepressant medication that has not been at stable dose for at least 3 months
20. Hospital Anxiety and Depression Scale (HADS) score of ≥11 for depression or anxiety items
21. Binge Eating Scale (BES) score of ≥27
22. Alcohol use disorder within the past year
23. Epilepsy
24. Currently taking phentermine or topiramate or the combination, or products containing these drugs
25. Currently taking stimulants (e.g., Attention Deficit Hyperactivity Disorder medications)
26. Current use of prescription or over-the-counter weight loss drugs or supplements
27. 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
28. Planning additional bariatric surgery procedures in the next 13 months
29. History of revisional bariatric surgery (revisional surgery after adjustable gastric banding is acceptable)
30. Currently participating in another weight loss program or have plans to participate in the next 13 months
31. Smoking cessation within the previous 3 months or plans to quit smoking in the next 13 months
32. Pregnant or breastfeeding or planning pregnancy in the coming 13 months
33. 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

Primary outcomes:
measure: Percent weight loss at Month 12 - Topiramate vs placebo
timeFrame: Month 0, Month 12
measure: Percent weight loss at Month 12 - Phentermine vs placebo
timeFrame: Month 0, Month 12
measure: Percent weight loss at Month 12 - Phentermine/Topiramate
timeFrame: Month 0, Month 12
Secondary outcomes:
measure: Energy intake
timeFrame: Month 0, Month 12
Other outcomes:
measure: Grazing
timeFrame: Months 0, 4, 12
measure: Loss-of-control eating
timeFrame: Months 0, 4, 12
measure: Binge eating
timeFrame: Months 0, 4, 12
Locations:
city: Orange
country: United States
facility: University of California Irvine Medical Center
state: California
Study officials:
affiliation: University of California, Irvine
name: Kishore M Gadde, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Noria SF, Shelby RD, Atkins KD, Nguyen NT, Gadde KM. Weight Regain After Bariatric Surgery: Scope of the Problem, Causes, Prevention, and Treatment. Curr Diab Rep. 2023 Mar;23(3):31-42. doi: 10.1007/s11892-023-01498-z. Epub 2023 Feb 8.