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

NCT05975580 | Recruiting Phase 4 DMC FDA Drug

• 2 other identifiers: 1849R01DK129936
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

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.

Conditions

Obesity

Keywords

Bariatric surgery; Weight regain; Antiobesity drugs; Treatment of weight regain

Outcome Measures

Primary Outcomes (3)

• Percent weight loss at Month 12 - Topiramate vs placebo

  Topiramate (Group 1 \[Group A + Group B\]) vs placebo (Group P)

  Month 0, Month 12

• Percent weight loss at Month 12 - Phentermine vs placebo

  Phentermine (Group 2 \[Group D + Group E) vs placebo (Group P)

  Month 0, Month 12

• 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 Outcomes (1)

• Energy intake

  Month 0, Month 12

Other Outcomes (3)

• Grazing

  Months 0, 4, 12

• Loss-of-control eating

  Months 0, 4, 12

• Binge eating

  Months 0, 4, 12

Study Arms (7)

Group A: Topiramate 50 mg

EXPERIMENTAL

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

Group B: Topiramate 100 mg

EXPERIMENTAL

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 15/100 mg during Months 5-12. Doses will be titrated in Month 5.

Drug: Topiramate

Group C: Phentermine 15 mg/Topiramate 100 mg

EXPERIMENTAL

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 15/100 mg during Months 5-12. Doses will be titrated in Month 5.

Drug: Topiramate; Drug: Phentermine

Group D: Phentermine 15 mg

EXPERIMENTAL

Phentermine will be started at 7.5 mg daily and the dose will be increased to 15 mg after 15 days. Responders at Month 4 will continue the same treatment until Month 12.

Drug: Phentermine

Group E: Phentermine 30 mg

EXPERIMENTAL

Nonresponders in the phentermine group at Month 4 will be re-randomized in a 1:1 ratio to receive phentermine 30 mg or phentermine/topiramate 15/100 mg during Months 5-12. Doses will be titrated in Month 5.

Drug: Phentermine

Group F: Phentermine 15 mg/Topiramate 100 mg

EXPERIMENTAL

Nonresponders in the phentermine group at Month 4 will be re-randomized in a 1:1 ratio to receive phentermine 30 mg or phentermine/topiramate 15/100 mg during Months 5-12. Doses will be titrated in Month 5.

Drug: Topiramate; Drug: Phentermine

Group P: Placebo

PLACEBO COMPARATOR

Placebo group will receive placebo.

Drug: Placebo

Interventions

Topiramate DRUG

Topiramate is an anticonvulsant (antiepilepsy) drug. IUPAC ID: 2,3:4,5-Bis-O-(1-methylethylidene)-beta-D-fructopyranose sulfamate

Group A: Topiramate 50 mg; Group B: Topiramate 100 mg; Group C: Phentermine 15 mg/Topiramate 100 mg; Group F: Phentermine 15 mg/Topiramate 100 mg

Phentermine DRUG

Phentermine belongs to a class of drugs called anorectics, also known as appetite suppressants. IUPAC name 2-methyl-1-phenylpropan-2-amine

Group C: Phentermine 15 mg/Topiramate 100 mg; Group D: Phentermine 15 mg; Group E: Phentermine 30 mg; Group F: Phentermine 15 mg/Topiramate 100 mg

Placebo DRUG

Placebo is an inactive substance.

Group P: Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female subjects aged 18-70 years
• Had sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB) at least 18 months 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of California, Irvine: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

University of California Irvine Medical Center

Orange, California, 92868, United States

RECRUITING

Related 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.

  PMID: 36752995 BACKGROUND

MeSH Terms

Conditions

Obesity

Interventions

Topiramate; Phentermine

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Fructose; Hexoses; Monosaccharides; Sugars; Carbohydrates; Ketoses; Amphetamines; Phenethylamines; Ethylamines; Amines; Organic Chemicals

Study Officials

• Kishore M Gadde, MD

  University of California, Irvine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Phuong Linh Huynh, MPH

CONTACT

7144566155; plhuynh@hs.uci.edu

Qin Wang

CONTACT

qinw15@hs.uci.edu

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor In Residence, Surgery

Model Details: 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.

Study Record Dates

• First Submitted: July 21, 2023
• First Posted: August 4, 2023
• Study Start: August 29, 2023
• Primary Completion (Estimated): April 30, 2027
• Study Completion (Estimated): July 31, 2027
• Last Updated: February 17, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)