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

Severe Obesity Clinical Trial

— GRABS-0  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06162715
• Other study ID #: VR72411
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: October 1, 2024
• Est. completion date: December 2027

Study information

• Verified date: June 2024
• Source: Vanderbilt University Medical Center
• Contact: Jason M Samuels, MD
• Phone: (615) 322 4504
• Email: jason.m.samuels[@]vumc.org
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. Patients who take tirzepatide 12 months after bariatric surgery will be compared to patients who receive a placebo.

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).

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 30
• Est. completion date: December 2027
• Est. primary completion date: January 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Obesity, Morbid
• Severe Obesity

Intervention

Drug:
• Tirzepatide
Tirzepatide will be initiated 12 months 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:
• 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.

Locations

Country	Name	City	State
United States	Vanderbilt University Medical Center	Nashville	Tennessee

Sponsors (1)

Lead Sponsor	Collaborator
Vanderbilt University Medical Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	weight regain after TRZ discontinuation	Degree of weight regain in intervention arm after discontinuation of TRZ	weeks 24 to 48
Other	Obesity remission	incidence of obesity remission (BMI < 30)	baseline to 24 weeks
Other	Remission of pre-existing comorbidities	Incidence of remission of Type 2 Diabetes, Hyperlipidemia, Hypertension	baseline to 24 weeks.
Other	change in anthropometric measurements	Changes in clinical obtained anthropometric measurements including waist circumference and waist-to-hip ratio	baseline to 24 weeks
Other	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.
Other	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
Other	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)
Other	Difference in acetaminophen AUC between groups	difference in acetaminophen AUC between Intervention and control groups	baseline to 24 weeks
Other	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
Other	Medication adherence	Incidence of missed doses, patient-driven drug discontinuation, patient withdrawal in intervention arm	baseline to 24 weeks
Other	Adverse events and healthcare resource utilization	Incidence of adverse events including emergency department visits, hospitalizations, and reoperations	baseline to 48 weeks
Primary	Weight loss	Change in weight over time.	baseline to 24 weeks
Secondary	Change in body composition	Changes in fat mass	baseline to 24 weeks
Secondary	Gastrointestinal symptoms	Gastroparesis Cardinal Symptom Index	baseline to 24 weeks
Secondary	Acetaminophen Area Under the Curve	Changes in acetaminophen area under the curve in the intervention arm	baseline to 24 weeks