Obesity
Conditions
Keywords
Bariatric surgery, Weight regain, Antiobesity drugs, Treatment of weight regain
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.
Interventions
DRUGTopiramate
Topiramate is an anticonvulsant (antiepilepsy) drug. IUPAC ID: 2,3:4,5-Bis-O-(1-methylethylidene)-beta-D-fructopyranose sulfamate
DRUGPhentermine
Phentermine belongs to a class of drugs called anorectics, also known as appetite suppressants. IUPAC name 2-methyl-1-phenylpropan-2-amine
DRUGPlacebo
Placebo is an inactive substance.
Sponsors
University of California, Irvine
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, 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.
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Contacts
CONTACTPhuong Linh Huynh, MPH
CONTACTQin Wang
PRINCIPAL_INVESTIGATORKishore M Gadde, MD
University of California, Irvine
Outcome results
None listed