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RECRUITING

NCT07058155

PHASE4

Optimizing Portal Hypertension With TIPS and Interval Metabolic Surgery for Advanced Liver Disease

Sponsor: The Cleveland Clinic

View on ClinicalTrials.gov

Summary

Cirrhosis is a form of advanced liver disease that can lead to serious complications, especially when combined with severe obesity. Many patients with cirrhosis also develop a condition called clinically significant portal hypertension (CSPH), which is increased pressure in the veins of the liver. CSPH raises the risk of life-threatening events like internal bleeding and liver failure. Unfortunately, treatment options for people who have both cirrhosis and severe obesity are very limited, especially when portal hypertension is present. This study, called the OPTIMAL Trial, is a randomized clinical trial designed to evaluate whether combining two procedures improves health outcomes in this high-risk population. The first procedure, called TIPS (Transjugular Intrahepatic Portosystemic Shunt), is a minimally invasive treatment that reduces pressure in the liver by creating a pathway for blood to flow more easily. The second procedure is sleeve gastrectomy, a form of metabolic (bariatric) surgery that helps patients lose weight and improve related conditions like diabetes. The study will compare two groups: 1. One group will receive TIPS followed by sleeve gastrectomy (TIPS+SG). 2. The other group will receive medical weight management (standard non-surgical care, including diet, lifestyle changes, and weight loss medications). All participants will have severe obesity and cirrhosis with CSPH but will not have decompensated liver disease (such as large amounts of fluid in the abdomen, a history of variceal bleeding, or recent liver failure). Eligible participants will be randomly assigned to one of the two groups. The main goal of the study is to determine whether the combination of TIPS + SG improves quality of life and leads to greater weight loss compared to medical therapy alone. The study will also monitor for any complications from either the procedures or the medical treatment. Participants will be followed for 6 months after their treatment starts, with periodic assessments of their physical health, liver function, and overall well-being. Some participants may also be followed for a longer period to assess long-term outcomes. This study hopes to provide high-quality evidence for a novel, stepwise treatment strategy that may help people with obesity and liver disease live longer, healthier lives. If successful, it could change how advanced liver disease and obesity are managed together, especially in patients who currently have few safe and effective options. All study care is provided at Cleveland Clinic, Cleveland, Ohio, USA.

Official title: OPTIMAL Trial: Optimizing Portal Hypertension With TIPS and Interval Metabolic Surgery for Advanced Liver Disease

Key Details

Gender

All

Age Range

18 Years - 70 Years

Study Type

INTERVENTIONAL

Enrollment

Start Date

2025-12-17

Completion Date

2034-02-01

Last Updated

2025-12-23

Healthy Volunteers

Conditions

Liver Cirrhoses Portal Hypertension Related to Cirrhosis Severe Obesity TIPS

Interventions

PROCEDURE

Transjugular Intrahepatic Portosystemic Shunt (TIPS)

Fluoroscopically guided placement of a covered stent creating a portosystemic shunt between hepatic and portal veins. Goal: ≥ 50 % HVPG reduction or final HVPG \< 12 mmHg. Conducted 4-6 weeks (≤ 6 months allowed) before bariatric surgery; standard post-TIPS surveillance ultrasound and EGD to confirm patency and variceal resolution.

PROCEDURE

Sleeve Gastrectomy

Longitudinal resection of \~80 % of stomach via laparoscopic or robotic approach, preserving pylorus. Performed after successful TIPS once portal pressures stabilize (\< 6 months post-TIPS). Standard peri-operative care, micronutrient supplementation, and bariatric follow-up per ASMBS guidelines.

DRUG

Anti-Obesity Pharmacotherapy (Class Effect)

Clinician-selected, evidence-based anti-obesity medications (AOMs) used at the treating provider's discretion. Agents may include incretin-based therapies (e.g., Semaglutide, Tirzepatide) or other FDA-approved AOMs such as Topiramate or Phentermine. Dosing and titration follow standard labeling; no specific drug is mandated. The study assesses the overall class effect of pharmacotherapy rather than any single agent.

BEHAVIORAL

Lifestyle Counseling - Diet & Physical-Activity Program

Regular sessions with a registered dietitian or equivalent (in-person or virtual) focusing on adherence to a reduced-calorie diet, structured physical-activity regimen, and behavior-change strategies. Counseling occurs throughout the 6-month study period and is considered standard care for this patient population.

Inclusion Criteria 1. Candidate for general anesthesia. 2. Age 18-70 years at consent. 3. BMI 35-70 kg/m² at first study visit. 4. Eligible for sleeve gastrectomy per ASMBS/IFSO 2022 guidelines. 5. Insurance coverage for metabolic surgery. 6. Current or prior anti-obesity medication use permitted. 7. Liver cirrhosis confirmed by biopsy or non-invasive assessment. 8. Clinically significant portal hypertension (HVPG ≥ 10 mm Hg, or esophagogastric varices / portal-hypertensive gastropathy, or imaging evidence of collaterals/dilated portal vein). 9. Able and willing to provide informed consent and comply with study procedures. 10. Women of child-bearing potential: negative urine pregnancy test at screening and randomization and agreement to reliable contraception for 2 years. Exclusion Criteria 1. Prior bariatric/metabolic surgery (except removed devices ≥ 3 months earlier). 2. Prior complex foregut surgery. 3. History of solid-organ transplant. 4. Severe pulmonary disease (FEV1 \< 50 % predicted). 5. Significant cardiac or atherosclerotic disease with planned re-vascularization within 12 months. 6. ASA class IV or V uncompensated cardiopulmonary disease. 7. Left-ventricular ejection fraction \< 25 % or MI/unstable angina/stroke/heart surgery/coronary stent within 6 months. 8. Hiatal hernia \> 7 cm or LA grade C/D erosive esophagitis. 9. Active Crohn's disease. 10. Severe psychiatric illness, dementia, active psychosis, history of suicide attempt, or alcohol/substance abuse within 12 months. 11. Pregnant, breastfeeding, planning pregnancy, or not using adequate contraception. 12. Malignancy within the prior 12 months (except non-melanoma skin cancer). 13. Life expectancy \< 2 years in investigator's judgment. 14. Investigational therapy within 3 months. 15. Acute pancreatitis ≤ 90 days. 16. Portal vein thrombosis at screening. 17. Decompensated cirrhosis (moderate/large ascites, hepatic encephalopathy, or listed for liver transplant); small ascites or prior variceal bleed allowed. 18. Total bilirubin \> 3 mg/dL, INR \> 1.7, or platelets \< 50 000/µL (within 1 month). 19. Significant alcohol intake (\> 14 units/week women, \> 21 units/week men) within the prior 12 months. 20. eGFR \< 45 mL/min/1.73 m² or on dialysis (within 1 month). 21. AIDS. 22. Unable to understand study or give consent. 23. Plans to move more than 3 hours from Cleveland within 6 months. 24. Previous randomization in this trial. 25. Any condition that, in the investigator's opinion, places the subject at undue risk.

Locations (1)

Cleveland Clinic Main Campus

Cleveland, Ohio, United States