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

Status: Recruiting
Location: See location...
Intervention Type: Drug, Behavioral, Procedure
Study Type: Interventional
Study Phase: Phase 4
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.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Maximum Age: 70
Healthy Volunteers: f
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• Candidate for general anesthesia.

• Age 18-70 years at consent.

• BMI 35-70 kg/m² at first study visit.

• Eligible for sleeve gastrectomy per ASMBS/IFSO 2022 guidelines.

• Insurance coverage for metabolic surgery.

• Current or prior anti-obesity medication use permitted.

• Liver cirrhosis confirmed by biopsy or non-invasive assessment.

• Clinically significant portal hypertension (HVPG ≥ 10 mm Hg, or esophagogastric varices / portal-hypertensive gastropathy, or imaging evidence of collaterals/dilated portal vein).

• Able and willing to provide informed consent and comply with study procedures.

⁃ Women of child-bearing potential: negative urine pregnancy test at screening and randomization and agreement to reliable contraception for 2 years.

Locations
United States
Ohio
Cleveland Clinic Main Campus
RECRUITING
Cleveland
Contact Information
Primary
Awwab F Hammad, MD
hammada4@ccf.org
+1 216 444 5022
Backup
Erlind Allkushi
ALLKUSE2@ccf.org
Time Frame
Start Date: 2025-09-20
Estimated Completion Date: 2034-02-01
Participants
Target number of participants: 70
Treatments
Experimental: TIPS + Sleeve Gastrectomy
Participants first undergo transjugular intrahepatic portosystemic shunt (TIPS) placement (target HVPG \< 12 mmHg or ≥ 50 % reduction). After portal pressure stabilization-ideally 4-6 weeks, allowed ≤ 6 months-they receive laparoscopic or robotic sleeve gastrectomy. Standard peri- and post-operative care, plus routine lifestyle counseling, are provided.
Active_comparator: Best-Option Medical Weight Management
Participants will follow an individualized, clinician-directed medical weight loss program that includes dietary and physical activity counseling, behavior modification strategies, and best available anti-obesity pharmacotherapy (e.g., GLP-1 receptor agonists, dual incretin agonists, first generation AOMs).
Sponsors
Leads: The Cleveland Clinic
Collaborators: Ali Aminian, MD

This content was sourced from clinicaltrials.gov