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

Обзор

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.

Подробное описание

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.

Вмешательства

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

Первичные конечные точки

• Percent weight loss at Month 12 - Topiramate vs placebo [Срок оценки: Month 0, Month 12]
• Percent weight loss at Month 12 - Phentermine vs placebo [Срок оценки: Month 0, Month 12]
• Percent weight loss at Month 12 - Phentermine/Topiramate [Срок оценки: Month 0, Month 12]

Вторичные конечные точки (1)

• Energy intake [Срок оценки: Month 0, Month 12]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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
• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Последовательный дизайн

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

США · 1 центр

• University of California Irvine Medical Center — Orange

Публикации

• 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

Идентификаторы

NCT: NCT05975580 · 1849 · R01DK129936

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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