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

Phase 2

• Conditions: Severe Obesity; Obesity; BMI Greater Than 30
• Interventions: Other: Standard of Care post-gastric bypass; Drug: Tirzepatide

• Registration Number: NCT06162715
• Lead Sponsor: Vanderbilt University Medical Center

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 receive a placebo.

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. 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).

Study Timeline

• Study First Submitted: 2023-11-30
• Study First Submitted QC: 2023-11-30
• Study First Posted: 2023-12-08
• Study Start: 2024-10-30
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-07
• Last Update Posted: 2025-03-10
• Primary Completion: 2027-01
• Study Completion: 2027-12

Recruitment & Eligibility

• Status: ENROLLING_BY_INVITATION
• Sex: All
• Target Recruitment: 30

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Control - Standard of care Post-Gastric Bypass Surgery	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.
Tirzepatide Group	Tirzepatide	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.

Primary Outcome Measures

Name	Time	Method
Weight loss	baseline to 24 weeks	Change in weight over time.

Secondary Outcome Measures

Name	Time	Method
Change in body composition	baseline to 24 weeks	Changes in fat mass
Gastrointestinal symptoms	baseline to 24 weeks	Gastroparesis Cardinal Symptom Index
Acetaminophen Area Under the Curve	baseline to 24 weeks	Changes in acetaminophen area under the curve in the intervention arm
Lean body mass	24 weeks	Utilizing DXA, we will determine changes in lean body mass in both arms

Trial Locations

Locations (1)

Vanderbilt University Medical Center; 🇺🇸 Nashville, Tennessee, United States