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

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.

Study Overview

• Status: Enrolling by invitation
• Conditions: Obesity; Severe Obesity; BMI Greater Than 30
• Intervention / Treatment: Other: Standard of Care post-gastric bypass; Drug: Tirzepatide

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).

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37209
      • Vanderbilt University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Subject must be able to understand and provide informed consent.
2. BMI > 30 12 months after bariatric surgery.
3. Age > 25 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	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 Names: Mounjaro; Zepbound
Other: 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.	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Weight loss	Change in weight over time.	baseline to 24 weeks
Gastrointestinal symptoms	We will measure the average PAGI SYM score from 0 - 24 weeks in both arms.	baseline to 24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in body composition	Changes in fat mass	baseline to 24 weeks
Acetaminophen Area Under the Curve	Changes in acetaminophen area under the curve in the intervention arm	baseline to 24 weeks
Lean body mass	Utilizing DXA, we will determine changes in lean body mass in both arms	baseline to 24 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
weight regain after TRZ discontinuation	Degree of weight regain in intervention arm after discontinuation of TRZ	weeks 24 to 48
Obesity remission	incidence of obesity remission (BMI < 30)	baseline to 24 weeks
Remission of pre-existing comorbidities	Incidence of remission of Type 2 Diabetes, Hyperlipidemia, Hypertension	baseline to 24 weeks.
change in anthropometric measurements	Changes in clinical obtained anthropometric measurements including waist circumference and waist-to-hip ratio	baseline to 24 weeks
changes in body composition	Changes in DXA-proven body composition including lean body mass and ratio of lean body mass to fat mass	baseline to 24 weeks.
Change in PAGI-SYM sub-scale scores	1. heartburn/regurgitation, 2. nausea/vomiting, 3. postprandial fullness, 4. bloating, 5. upper and lower abdominal pain	baseline to 24 weeks
change in PAGI-SYM scores in the TRZ arm	Determining evolution of PAGI-SYM scores across treatment in both arms and after discontinuation of TRZ in the intervetion arm.	baseline to week 24 and week 24 to week 28 (after TRZ discontinuation)
Difference in acetaminophen AUC between groups	difference in acetaminophen AUC between Intervention and control groups	baseline to 24 weeks
Changes in response to mixed meal tolerance test	change in intervention arm mixed meal AUC for Glucose, Insulin, and GLP-1	baseline to 24 weeks
Medication adherence	Incidence of missed doses, patient-driven drug discontinuation, patient withdrawal in intervention arm	baseline to 24 weeks
Adverse events and healthcare resource utilization	Incidence of adverse events including emergency department visits, hospitalizations, and reoperations	baseline to 48 weeks

Collaborators and Investigators

• Sponsor: Vanderbilt University Medical Center
• Investigators: Principal Investigator: Jason M Samuels, MD, Vanderbilt University Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): October 30, 2024
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: November 30, 2023
• First Submitted That Met QC Criteria: November 30, 2023
• First Posted (Actual): December 8, 2023

Study Record Updates

• Last Update Posted (Actual): June 3, 2026
• Last Update Submitted That Met QC Criteria: June 1, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Obesity; bariatric surgery; Roux-en-Y Gastric Bypass; Tirzepatide; GLP-1 Receptor Agonists
• Additional Relevant MeSH Terms: Nutrition Disorders; Overnutrition; Body Weight; Overweight; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Obesity; Obesity, Morbid; Amino Acids, Peptides, and Proteins; Proteins; Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptide Receptors; Receptors, G-Protein-Coupled; Receptors, Cell Surface; Membrane Proteins; Receptors, Gastrointestinal Hormone; Receptors, Peptide; Tirzepatide
• Other Study ID Numbers: VR72411

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All participant-level data will be preserved and shared. Shared data will be deidentified prior to sharing. Clinicaltrials.gov will document recruitment progress and final results. Study protocols will be shared with publications as supplementary data and made available upon request. All participant consent document will be collected and stored electronically utilizing the REDCap study data repository. The REDCap data warehouse will also contain the study data dictionary. Study protocols have also been published on the ClinicalTrials.gov and any protocol amendments will be reflected on the ClinicalTrials.gov study page. The investigators will utilize the Research Electronic Data Capture (REDCap) data warehouse maintained locally at Vanderbilt for all data collection. Upon study completion and prior to closing the REDCap data warehouse for this study, the investigators will archive all data after removing patient identifiers in the Open Science Framework data repository.
• IPD Sharing Time Frame: Per institutional policy, data will be maintained in the local REDCap data repository for 6 years after closure of the study. Following this period, data will be deidentified and uploaded to the OSF repository, which has funding for at least 50 years of data storage.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No