ObesityPhase 4PROJECT-BARINCT05975580
Pharmacotherapy in Conjunction With Lifestyle Counseling for Management of Weight Regain After Bariatric Surgery
A Phase 4 study testing Topiramate and Phentermine in people with Obesity, run by University of California, Irvine at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Obesity
- What is being tested?
- Topiramate and Phentermine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 120 participants
- Where
- 1 siteUnited States
- Study dates
- 29 Aug 2023to 31 Jan 2028
- Phase
- Phase 4
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Melanie Morales Vargas contact
United States1 site, 1 recruiting
- Recruiting
University of California Irvine Medical Center
Orange, California, 92868
Raha Esmaeili, rahae@hs.uci.edu
Melanie Morales Vargas, msmoral2@hs.uci.edu
About this study
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.
Read the 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.
- Conditions
- Obesity
- Being tested
- Topiramate, Phentermine, Placebo
- Keywords
- Bariatric surgery, Weight regain, Antiobesity drugs, Treatment of weight regain
- Medical subject headings
- Obesity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TopiramateDrug
Topiramate is an anticonvulsant (antiepilepsy) drug. IUPAC ID: 2,3:4,5-Bis-O-(1-methylethylidene)-beta-D-fructopyranose sulfamate
PhentermineDrug
Phentermine belongs to a class of drugs called anorectics, also known as appetite suppressants. IUPAC name 2-methyl-1-phenylpropan-2-amine
PlaceboDrug
Placebo is an inactive substance.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: Drug: Topiramate; Drug: Phentermine |
| Group P: Placebo | Placebo comparator | Placebo group will receive placebo. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent weight loss at Month 12 - Topiramate vs placebo
Topiramate (Group 1 [Group A + Group B]) vs placebo (Group P)
Measured: Month 0, Month 12
Percent weight loss at Month 12 - Phentermine vs placebo
Phentermine (Group 2 [Group D + Group E) vs placebo (Group P)
Measured: Month 0, Month 12
Percent weight loss at Month 12 - Phentermine/Topiramate
Phentermine/Topiramate (Group 3 [Group C + Group F]) vs placebo (Group P)
Measured: Month 0, Month 12
Secondary outcomes (1)
Energy intake
Change in energy intake in kcal/d assessed with a dietitian interview. Comparisons between Groups 1, 2, 3 vs placebo.
Measured: Month 0, Month 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Aug 2023
- Study start29 Aug 2023
- Primary completion31 Jul 2027 (estimated)
- Study completion31 Jan 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for ObesityStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- 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.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of California, Irvine
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Kishore M Gadde, MD, University of California, Irvine
- Investigators
- Kishore M Gadde, MD, Principal investigator, University of California, Irvine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05975580
- Sponsor's protocol ID
- 1849
- Other IDs
- R01DK129936
- Acronym
- PROJECT-BARI
- Status last verified
- Oct 2026
- First submitted
- 21 Jul 2023
- Last updated
- 19 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 36752995