GLP-1 Receptor Agonists Post-Bariatric Surgery (GRABS) Pilot Trial (GRABS-0)

Vanderbilt University Medical Center

Status and phase: Invitation-only; Phase 3; Phase 2

Conditions: Obesity; BMI Greater Than 30; Severe Obesity

Treatments: Other: Standard of Care post-gastric bypass; Drug: Tirzepatide

Study type: Interventional

Funder types: Other

Identifiers

NCT06162715

VR72411

Details and patient eligibility

About

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.

Full 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).

Enrollment: 30 estimated patients

Sex: All

Ages: 30 to 65 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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30 participants in 2 patient groups

Tirzepatide Group

Experimental group

Description:

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.

Treatment:

Drug: Tirzepatide

Control - Standard of care Post-Gastric Bypass Surgery

Other group

Description:

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.

Treatment:

Other: Standard of Care post-gastric bypass