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

Conditions

• Liver Cirrhoses
• Portal Hypertension Related to Cirrhosis
• Severe Obesity
• TIPS

Eligibility Criteria

Sex

ALL

Age

18 Years - 70 Years

Healthy Volunteers

Not accepted

Interventions

• Transjugular Intrahepatic Portosystemic Shunt (TIPS) — PROCEDURE
  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.
• Sleeve Gastrectomy — PROCEDURE
  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.
• Anti-Obesity Pharmacotherapy (Class Effect) — DRUG
  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.
• Lifestyle Counseling - Diet & Physical-Activity Program — BEHAVIORAL
  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.

Study Details

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.

Key Dates

Start date

Dec 17, 2025

Status verified

Dec 2025

Primary completion

Feb 1, 2029

Completion

Feb 1, 2034

Study Design

Enrollment

70 participants (estimated)

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• 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).

Primary Outcome Measure

Change in SF-36 Physical Component Summary (PCS) Score From Baseline to 6 Months [ Time Frame: At 6 months after treatment initiation (Day 0 = TIPS placement date or start of medical management). ]

Central Contacts

• Awwab F Hammad, MD
  +1 216 444 5022
  [email protected]
• Erlind Allkushi
  [email protected]

Locations (1)

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