BMI Greater Than 30, Obesity, Severe Obesity
Conditions
Keywords
bariatric surgery, Roux-en-Y Gastric Bypass, GLP-1 Receptor Agonists, Tirzepatide, Obesity
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 continue with the current standard of care for patients who have previously undergone Gastric Bypass Surgery.
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).
Interventions
DRUGTirzepatide
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.
OTHERStandard 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.
Sponsors
Vanderbilt University Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
25 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Weight loss | baseline to 24 weeks | Change in weight over time. |
| Gastrointestinal symptoms | baseline to 24 weeks | We will measure the average PAGI SYM score from 0 - 24 weeks in both arms. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in body composition | baseline to 24 weeks | Changes in fat mass |
| Acetaminophen Area Under the Curve | baseline to 24 weeks | Changes in acetaminophen area under the curve in the intervention arm |
| Lean body mass | baseline to 24 weeks | Utilizing DXA, we will determine changes in lean body mass in both arms |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORJason M Samuels, MD
Vanderbilt University Medical Center
Outcome results
None listed