Severe ObesityPhase 2/3GRABS-0NCT06162715
GLP-1 Receptor Agonists Post-Bariatric Surgery (GRABS) Pilot Trial
A Phase 2/3 study testing Tirzepatide in people with Severe Obesity and Obesity, run by Vanderbilt University Medical Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 25 to 65 years
- Conditions the study is for
- Severe Obesity, Obesity, BMI Greater Than 30
- What is being tested?
- Tirzepatide
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- 30 Oct 2024to 1 Dec 2027
- Phase
- Phase 2/3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 25 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subject must be able to understand and provide informed consent.
- BMI > 30 12 months after bariatric surgery.
- Age > 25 and < 65
- Patients undergoing primary Roux-en-Y Gastric Bypass
Who cannot join
- Inability or unwillingness of a subject to give written informed consent or comply with the study protocol.
- Diagnosis of type I Diabetes
- Revisional bariatric surgery (prior adjustable gastric band, sleeve gastric, vertical banded gastroplasty).
- Use of medications for type 2 di
- Hemoglobin A1c > 8.5 in last 3 months.
- Patient-reported Tobacco, e-cigarette, or smoked marijuana use within 12 months As this would preclude patients from undergoing bariatric surgery.
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- Personal history of pancreatitis as determined by history.
- Personal or family history of medullary thyroid cancer by history or multiple endocrine neoplasia syndrome type 2
- Pregnancy by urine testing, current lactation, or plans to become pregnant during the study period.
- Use of systemic glucocorticoids in the past 28 days
- Myocardial infarction, unstable angina, stroke, or heart failure (NYHA class II) within 1 year by history.
- History of solid organ transplant.
- History of physician-diagnosed malignancy (other than excised non-melanoma skin cancer) in the past 5 years.
- Current uncontrolled hypertension (systolic >150, diastolic >90) or untreated hyperthyroidism.
- 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.
- Screening creatinine elevation with EGFR < 60 at time of randomization.
- Tobacco use in last 12 months
- Pregnancy
- Prisoners
- Unable or unwilling to follow-up
- Unable to understand English/Spanish
Trial locations and contacts
1 site in 1 country.
United States1 site
Vanderbilt University Medical Center
Nashville, Tennessee, 37209
About this study
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.
Read the 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
- Being tested
- Tirzepatide, Standard of Care post-gastric bypass
- Keywords
- bariatric surgery, Roux-en-Y Gastric Bypass, GLP-1 Receptor Agonists, Tirzepatide, Obesity
- Medical subject headings
- Obesity, Morbid, Obesity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TirzepatideDrug
Also called Zepbound, Mounjaro
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.
Standard of Care post-gastric bypassOther
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.
| Study group | Role | What they receive |
|---|---|---|
| Tirzepatide Group | Experimental | 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. Receives: Drug: Tirzepatide |
| Control - Standard of care Post-Gastric Bypass Surgery | 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 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. Receives: Other: Standard of Care post-gastric bypass |
What is being measured
The primary outcome is the main question the study is designed to answer.
Weight loss
Change in weight over time.
Measured: baseline to 24 weeks
Gastrointestinal symptoms
We will measure the average PAGI SYM score from 0 - 24 weeks in both arms.
Measured: baseline to 24 weeks
Secondary outcomes (3)
Change in body composition
Changes in fat mass
Measured: baseline to 24 weeks
Acetaminophen Area Under the Curve
Changes in acetaminophen area under the curve in the intervention arm
Measured: baseline to 24 weeks
Lean body mass
Utilizing DXA, we will determine changes in lean body mass in both arms
Measured: baseline to 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Dec 2023
- Study start30 Oct 2024
- Primary completion1 Jan 2027 (estimated)
- Study completion1 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Severe ObesityStudies of the same condition, open and under way.
- More trials run by Vanderbilt University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Vanderbilt University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jason Samuels, Vanderbilt University Medical Center
- Investigators
- Jason M Samuels, MD, Principal investigator, Vanderbilt University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06162715
- Sponsor's protocol ID
- VR72411
- Acronym
- GRABS-0
- Status last verified
- Aug 2026
- First submitted
- 30 Nov 2023
- Last updated
- 4 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Publications
Samuels JM, Williams CR, Patel MB, Self WH, Funk LM, Roumie C, Spann MD, Northup CJ, Ye F, Irlmeier R, Sohn I, Zhu Y, Niswender K. GLP-1 Receptor Agonists Post-Bariatric Surgery (GRABS) Trial: Rationale, Design and Baseline Characteristics. Diabetes Obes Metab. 2026 Sep 8. doi: 10.1111/dom.71320. Online ahead of print.
PubMed 42712125