NCT06162715

GLP-1 Receptor Agonists Post-Bariatric Surgery (GRABS) Pilot Trial

• Status: Enrolling By Invitation
• Phase: Phase 2 / Phase 3
• Study type: Interventional
• Enrollment: 30 (estimated)
• Sponsor: Vanderbilt University Medical Center · Academic / Other
• Sex: All
• Age: 25 Years – 65 Years
• Healthy volunteers: Not accepted

Summary

The goal of this pilot clinical trial is to determine the effectiveness of Tirzepatide in patients with persistent obesity (BMI \> 30) 12 months after bariatric surgery (Roux-en-Y Gastric Bypass). The investigators also aim to determine the frequency of side effects with Tirzepatide in this patient population. Patients who take tirzepatide 12 months after bariatric surgery will be compared to patients who continue with the current standard of care for patients who have previously undergone Gastric Bypass Surgery.

Detailed description

Obesity affects nearly half of the U.S. population, impacting health outcomes including diabetes, cardiovascular risk, longevity, and quality of life. While bariatric surgery such as gastric bypass stands as the most effective intervention, 65% of individuals experience persistent obesity when undergoing surgical weight loss alone. Given the wide-ranging impact of obesity on health outcomes, a critical need exists to explore the efficacy of adjuvant weight loss therapies after gastric bypass surgery. Tirzepatide (TRZ), a type of glucagon-like peptide-1 receptor agonist, shows remarkable effectiveness in medical obesity with 25% weight loss after sustained therapy. However, nearly two-thirds of patients taking medications like TRZ have mild to moderate gastrointestinal (GI) symptoms, including nausea, vomiting, and abdominal pain. These medication side-effects could be a consequence of gastroparesis via vagal stimulation of the stomach, and may represent a major driver of weight loss. Limited data exist regarding use of these newer agents, such as TRZ, in patients who have undergone gastric bypass, which disrupts vagal nerves responsible for managing food transit and gastric emptying. This is a major and timely scientific gap in understanding whether gastric bypass surgery might mitigate these GI symptoms while allowing for enhanced weight loss with adjuvant TRZ use in the post-operative period. The investigators propose a pilot, phase II, open-label trial enrolling patients twelve months after gastric bypass with a nadir Body Mass Index ≥ 30 kg/m2. Study subjects will be randomized to either 24 weeks of TRZ or post-surgery standard of care. Subjects randomized to the standard of care arm will crossover to receive the intervention drug after 24 weeks of observation. Our proposal consists of two aims. First, the investigators will determine the impact of adjuvant TRZ administration on weight, total fat mass, and lean body mass in patients with a history of gastric bypass (Aim 1). Second, the investigators aim to investigate the frequency and severity of GI discomfort associated with TRZ utilizing a validated patient reported outcome questionnaire, and they will investigate the impact of TRZ on GI motility in patients with prior Gastric Bypass (Aim 2).

Conditions

• Severe Obesity
• Obesity
• BMI Greater Than 30

Interventions

Type	Name	Description
DRUG	Tirzepatide	Tirzepatide will be initiated 12 or 18 months (12 months + 24 weeks) after patients undergo Roux-en-Y Gastric Bypass. Patients will be started on the lowest dose of 2.5 mg and the dose increased every 6 weeks following an adaptive maximum dose titration protocol. Patients will then complete a final 4 weeks of the study drug.
OTHER	Standard of Care post-gastric bypass	Patients randomized to the control arm will receive the standard of care for weight maintenance after gastric bypass including dietary guidance provided by the Vanderbilt Surgical Weight Loss handbook. This includes recommendations for 64 oz of fluids per day, ≥60 grams of protein/day, and daily bariatric multivitamins. Patients will continue to have access to dedicated bariatric dietitians, advanced practice providers, and surgeons on an ad hoc basis per patients' request.

Timeline

• Start date: 2024-10-30
• Primary completion: 2027-05-01
• Completion: 2027-12-01
• First posted: 2023-12-08
• Last updated: 2026-03-09

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study