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

Obesity Clinical Trial

— PROJECT-BARI  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05975580
• Other study ID #: 1849
• Secondary ID: R01DK129936
• Status: Recruiting
• Phase: Phase 4
• Start date: August 29, 2023
• Est. completion date: July 31, 2027

Study information

• Verified date: August 2023
• Source: University of California, Irvine
• Contact: Phuong Linh Huynh, MPH
• Phone: 7144566155
• Email: plhuynh[@]hs.uci.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: July 31, 2027
• Est. primary completion date: April 2, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

1. Male and female subjects aged 18-70 years

2. Had sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB) between =18 months and =10 years 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

Related Conditions & MeSH terms

• Obesity

Intervention

Drug:
• Topiramate
Topiramate is an anticonvulsant (antiepilepsy) drug. IUPAC ID: 2,3:4,5-Bis-O-(1-methylethylidene)-beta-D-fructopyranose sulfamate
• Phentermine
Phentermine belongs to a class of drugs called anorectics, also known as appetite suppressants. IUPAC name 2-methyl-1-phenylpropan-2-amine
• Placebo
Placebo is an inactive substance.

Locations

Country	Name	City	State
United States	University of California Irvine Medical Center	Orange	California

Sponsors (2)

Lead Sponsor	Collaborator
University of California, Irvine	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Country where clinical trial is conducted

United States, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Grazing	Change in grazing behavior, assessed with the Grazing Questionnaire. Comparisons between Groups 1, 2, 3 vs placebo.	Months 0, 4, 12
Other	Loss-of-control eating	Change in loss-of-control eating, assessed with the Loss-of-Control Eating Scale. Comparisons between Groups 1, 2, 3 vs placebo.	Months 0, 4, 12
Other	Binge eating	Change in binge eating, assessed with the Binge Eating Scale. Comparisons between Groups 1, 2, 3 vs placebo.	Months 0, 4, 12
Primary	Percent weight loss at Month 12 - Topiramate vs placebo	Topiramate (Group 1 [Group A + Group B]) vs placebo (Group P)	Month 0, Month 12
Primary	Percent weight loss at Month 12 - Phentermine vs placebo	Phentermine (Group 2 [Group D + Group E) vs placebo (Group P)	Month 0, Month 12
Primary	Percent weight loss at Month 12 - Phentermine/Topiramate	Phentermine/Topiramate (Group 3 [Group C + Group F]) vs placebo (Group P)	Month 0, Month 12
Secondary	Energy intake	Change in energy intake in kcal/d assessed with a dietitian interview. Comparisons between Groups 1, 2, 3 vs placebo.	Month 0, Month 12