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

NCT ID: NCT06162715

Last Updated: 2025-12-05

Basic Information

• Recruitment Status: ENROLLING_BY_INVITATION
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-10-30
• Study Completion Date: 2027-12-31

Brief 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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Tirzepatide Group

Participants in the TRZ cohort will initiate a standardized dose titration as described in the package insert. Participants will begin TRZ at 2.5 mg for four weeks and then increase by 2.5 mg every 4 weeks to a maximum dose of 15 mg. If subjects experience intolerable GI symptoms, they will be allowed to decrease to a lower dose by 2.5 mg for 2 weeks, at which point another attempt at an increased dose will be trialed. Should patients not tolerate a higher dose a second time, they will have the dose again lowered by 2.5 mg and kept at the lower dose for the remainder of the study, except for patients who do not tolerate two attempts at 5 mg. For patients who fail to titrate to at least 5 mg TRZ, a third attempt at an increased dose will be attempted 4 weeks after the second decrease in dose. These patients will then remain on 5 mg for the remainder of the intervention period. All participants receiving TRZ will be pooled in terms of outcomes measures.

Group Type: EXPERIMENTAL

Tirzepatide

Intervention Type: DRUG

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.

Control - Standard of care Post-Gastric Bypass Surgery

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 for 24 weeks. After 24 weeks, particiapnts in the control arm will crossover to the Tirzepatide arm and receive 24 weeks of TRZ following the same titration.

Group Type: OTHER

Standard of Care post-gastric bypass

Intervention Type: OTHER

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.

Interventions

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.

Intervention Type: DRUG

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.

Intervention Type: OTHER

Other Intervention Names

Zepbound; Mounjaro

Eligibility Criteria

Inclusion Criteria

1. Subject must be able to understand and provide informed consent.

2. BMI > 30 12 months after bariatric surgery.

3. Age > 30 and < 65

4. Patients undergoing primary Roux-en-Y Gastric Bypass

Exclusion Criteria

1. Inability or unwillingness of a subject to give written informed consent or comply with the study protocol.

2. Diagnosis of type I Diabetes

3. Revisional bariatric surgery (prior adjustable gastric band, sleeve gastric, vertical banded gastroplasty).

4. Use of medications for type 2 di

5. Hemoglobin A1c > 8.5 in last 3 months.

6. Patient-reported Tobacco, e-cigarette, or smoked marijuana use within 12 months As this would preclude patients from undergoing bariatric surgery.

7. Personal history of pancreatitis as determined by history.

8. Personal or family history of medullary thyroid cancer by history or multiple endocrine neoplasia syndrome type 2

9. Pregnancy by urine testing, current lactation, or plans to become pregnant during the study period.

10. Use of systemic glucocorticoids in the past 28 days

11. Myocardial infarction, unstable angina, stroke, or heart failure (NYHA class II) within 1 year by history.

12. History of solid organ transplant.

13. History of physician-diagnosed malignancy (other than excised non-melanoma skin cancer) in the past 5 years.

14. Current uncontrolled hypertension (systolic >150, diastolic >90) or untreated hyperthyroidism.

15. Current, diagnosed, or self-reported drug or alcohol abuse that, in the opinion of the investigator, would interfere with the subject's ability to comply with study requirements.

16. Screening creatinine elevation with EGFR < 60 at time of randomization.

17. Tobacco use in last 12 months

18. Pregnancy

19. Prisoners

20. Unable or unwilling to follow-up

21. Unable to understand English/Spanish

• Minimum Eligible Age: 30 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Vanderbilt University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Jason Samuels

Assistant Professor of Surgery

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jason M Samuels, MD

Role: PRINCIPAL_INVESTIGATOR

Vanderbilt University Medical Center

Locations

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Countries

United States

Provided Documents

Document Type: Informed Consent Form

View Document

Other Identifiers

VR72411

Identifier Type: -

Identifier Source: org_study_id