Bariatric Surgery, Obesity and Obesity-related Medical Conditions
Conditions
Brief summary
This clinical trial will test whether preoperative tirzepatide treatment improves outcomes after bariatric surgery. The outcome of this study could impact therapeutic guidelines for the multimodal treatment of obesity. The major objectives are: 1. To evaluate whether pre-operative tirzepatide treatment reduces tissue and circulating inflammatory markers at the time of surgery. 2. To establish the relationship of these changes with postoperative improvements in weight loss, metabolic and inflammatory profiles, comorbidity resolution (glycemic control, blood pressure, lipid profile), and 30-day surgical complications. Researchers will compare data from patients taking tirzepatide to data from patients not taking tirzepatide before their planned bariatric surgery to see if tirzepatide reduces inflammation and improves health outcomes after bariatric surgery. Participants will: Take or not take tirzepatide, depending on what study group they are in, once a week for 3 months. Visit the endocrine clinic once a month for 3 months to be prescribed the drug and for checkups regarding side effects due to the drug. Keep a diary to document taking the drug and any side effects. Continue with their planned bariatric surgery and post-surgery follow-ups according to their healthcare provider.
Interventions
DRUGtirzepatide
Participants will be educated on dietary and lifestyle changes. Participants will self inject 2.5 mg tirzepatide subcutaneously once weekly and maintain a drug administration diary. Dose escalation will proceed per package directions if instructed by study team at follow up visits.
BEHAVIORALStandard of Care
Participants will be educated on dietary and lifestyle changes
Sponsors
Marlene Starr
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* adults who have been enrolled in the multidisciplinary metabolic and bariatric surgery program at the UK HealthCare Weight Loss Surgery Clinic and are scheduled to receive laparoscopic or robotic sleeve gastrectomy, or gastric bypass surgery * BMI greater than or equal to 40 kg/m2 with one or more obesity-related comorbidities * have demonstrated abstinence from any form of nicotine use, confirmed by serum nicotine and metabolite testing * enrollment in the ADORE Bariatric Tissue Bank (IRB #69767)
Exclusion criteria
* any contraindication to the use of tirzepatide (per package insert) * Personal or family history of medullary thyroid carcinoma * Patients with Multiple Endocrine Neoplasm syndrome type 2 * Hypersensitivity to tirzepatide * History of pancreatitis * Type 1 Diabetes * patients with active, untreated or symptomatic cholelithiasis or jaundice * consistent use of a GLP-1 or GLP-1/GIP receptor agonist, over the past 90 days * diagnosed autoimmune disease * current use of immunosuppressive agents or use within the past 30 days * moderate or severe substance use disorder according to DSM-5 criteria * uncontrolled significant psychiatric disorder as assessed by specialized bariatric psychologist * female participant who is pregnant, breast-feeding, or intends to become pregnant with in 1 year following surgery * a prisoner
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in inflammatory markers c reactive protein (CRP) | Baseline and 3 months post-drug | Inflammatory marker will be measured by ELISA in blood samples drawn from patient. |
| Change in inflammatory markers interleukin 6 (IL-6) | Baseline and 3 months post-drug | Inflammatory marker will be measured by ELISA in blood samples drawn from patient. |
| Change in inflammatory markers tumor necrosis factor (TNF) | Baseline and 3 months post-drug | Inflammatory marker will be measured by ELISA in blood samples drawn from patient. |
| change in inflammatory markers (leptin) | Baseline and 3 months post-drug | Inflammatory marker will be measured by ELISA in blood samples drawn from patient. |
| change in inflammatory markers (adiponectin) | Baseline and 3 months post-drug | Inflammatory marker will be measured by ELISA in blood samples drawn from patient. |
| change in inflammatory markers renin-angiotensin-aldosterone system (RAAS) | Baseline and 3 months post-drug | Inflammatory markers will be measured by ELISA in blood samples drawn from patient. |
| RNA sequencing | at time of surgery | Bulk RNA sequencing analyses will be performed on tissue samples of fat and liver collected at the time of surgery |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in weight | Baseline, 3 months post-drug, 1-, 6-, and 12-months post surgery | patient weight will be measured |
| 30-day surgical complications | 1-,6-, and 12-months post surgery | Surgical complications will be assessed as standard of care and data evaluated for this study |
| change in inflammatory markers c reactive protein (CRP) | 1-, 6-, and 12-months post surgery | Inflammatory marker will be measured by ELISA in blood samples drawn from patient. |
| change in inflammatory markers interleukin 6 (IL-6) | 1-, 6-, and 12-months post surgery | Inflammatory marker will be measured by ELISA in blood samples drawn from patient. |
| change in inflammatory markers tumor necrosis factor (TNF) | 1-, 6-, and 12-months post surgery | Inflammatory marker will be measured by ELISA in blood samples drawn from patient. |
| change in inflammatory markers (leptin) | 1-, 6-, and 12-months post surgery | Inflammatory marker will be measured by ELISA in blood samples drawn from patient. |
| change in inflammatory markers (adiponectin) | 1-, 6-, and 12-months post surgery | Inflammatory marker will be measured by ELISA in blood samples drawn from patient. |
| change in inflammatory markers renin-angiotensin-aldosterone system (RAAS) | 1-, 6-, and 12-months post surgery | Inflammatory marker will be measured by ELISA in blood samples drawn from patient. |
| change in blood pressure | Baseline, 3 months post-drug, 1-, 6-, and 12-months post surgery | blood pressure per standard method in clinic |
| Change in Hemoglobin A1c | Baseline, 3 months post-drug, 1-, 6-, and 12-months post surgery | HbA1c will be measured by clinic lab |
| change in blood glucose | Baseline, 3 months post-drug, 1-, 6-, and 12-months post surgery | blood glucose will me measured in clinic lab |
| change in cholesterol | Baseline, 3 months post-drug, 1-, 6-, and 12-months post surgery | cholesterol measured in clinic lab |
| change in high-density lipoprotein (HDL) | Baseline, 3 months post-drug, 1-, 6-, and 12-months post surgery | high-density lipoprotein (HDL) measured in clinic lab |
| change in low-density lipoprotein (LDL) | Baseline, 3 months post-drug, 1-, 6-, and 12-months post surgery | low-density lipoprotein measured by clinic lab |
| change in triglycerides | Baseline, 3 months post-drug, 1-, 6-, and 12-months post surgery | triglycerides measured in clinic lab |
| change in insulin | Baseline, 3 months post-drug, 1-, 6-, and 12-months post surgery | insulin measured in clinic lab |
Countries
United States
Contacts
CONTACTMarlene Starr, PhD
CONTACTVarun Jain, MD
PRINCIPAL_INVESTIGATORMarlene Starr, PhD
University of Kentucky
STUDY_DIRECTORVarun Jain, MD
University of Kentucky
STUDY_DIRECTORWilliam B Inabnet, MD
University of Kentucky
STUDY_DIRECTORSimon J Fisher, MD. PhD
University of Kentucky
STUDY_DIRECTORPhilip A Kern, MD
University of Kentucky
STUDY_DIRECTORBarbara Nikolajczyk, PhD
University of Kentucky
Outcome results
None listed