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

NCT07058155 | Recruiting Phase 4 DMC FDA Drug

• 1 other identifier: 25-421
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

Brief 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. 1.One group will receive TIPS followed by sleeve gastrectomy (TIPS+SG).
2. 2.The other group will receive medical weight management (standard non-surgical care, including diet, lifestyle changes, and weight loss medications).

Conditions

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

Keywords

Sleeve Gastrectomy; Transjugular Intrahepatic Portosystemic Shunt (TIPS); Bariatric Surgery / Metabolic Surgery; Clinically Significant Portal Hypertension (CSPH); Health-Related Quality of Life (HRQOL); SF-36 Questionnaire; Weight Loss; Metabolic Dysfunction-Associated Steatohepatitis (MASH); Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD); Randomized Controlled Trial

Outcome Measures

Primary Outcomes (1)

• Change in SF-36 Physical Component Summary (PCS) Score From Baseline to 6 Months

  Difference between baseline and 6-month SF-36 PCS score (0-100 scale; higher values = better physical health-related quality of life). Positive change denotes improvement.

  At 6 months after treatment initiation (Day 0 = TIPS placement date or start of medical management).

Secondary Outcomes (6)

• Percent Total Body-Weight Loss (%TBWL) at 6 Months

  At 6 months after treatment initiation

• Incidence of Serious Complication Composite Within 6 Months

  Up to 6 months after treatment initiation

• Change in SF-36 Physical Component Score From Baseline to 1 Month

  Baseline and 1 month

• Change in SF-36 Mental Component Score From Baseline to 1 Month.

  Baseline and 1 month.

• Change in SF-36 Physical Component Score From Baseline to 3 Months

  Baseline and 3 months

Other Outcomes (1)

• Change in HbA1c (%)

  Baseline and 6 months (Week 24) after treatment initiation

Study Arms (2)

TIPS + Sleeve Gastrectomy

EXPERIMENTAL

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.

Procedure: Transjugular Intrahepatic Portosystemic Shunt (TIPS); Procedure: Sleeve Gastrectomy; Behavioral: Lifestyle Counseling - Diet & Physical-Activity Program

Best-Option Medical Weight Management

ACTIVE COMPARATOR

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).

Drug: Anti-Obesity Pharmacotherapy (Class Effect); Behavioral: Lifestyle Counseling - Diet & Physical-Activity Program

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.

Also known as: TIPS

TIPS + Sleeve Gastrectomy

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.

Also known as: SG

TIPS + Sleeve Gastrectomy

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.

Also known as: GLP-1 receptor agonist, Topiramate, Phentermine, Incretin Mimetics

Best-Option Medical Weight Management

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.

Also known as: Dietary modification, Exercise counseling, Behavioral weight-loss coaching

Best-Option Medical Weight Management; TIPS + Sleeve Gastrectomy

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• Prior bariatric/metabolic surgery (except removed devices ≥ 3 months earlier).
• Prior complex foregut surgery.
• History of solid-organ transplant.
• Severe pulmonary disease (FEV1 \< 50 % predicted).
• Significant cardiac or atherosclerotic disease with planned re-vascularization within 12 months.
• ASA class IV or V uncompensated cardiopulmonary disease.
• Left-ventricular ejection fraction \< 25 % or MI/unstable angina/stroke/heart surgery/coronary stent within 6 months.
• Hiatal hernia \> 7 cm or LA grade C/D erosive esophagitis.
• Active Crohn's disease.
• Severe psychiatric illness, dementia, active psychosis, history of suicide attempt, or alcohol/substance abuse within 12 months.
• Pregnant, breastfeeding, planning pregnancy, or not using adequate contraception.
• Malignancy within the prior 12 months (except non-melanoma skin cancer).
• Life expectancy \< 2 years in investigator's judgment.
• Investigational therapy within 3 months.
• Acute pancreatitis ≤ 90 days.

Sponsors & Collaborators

• The Cleveland Clinic: lead
• Ali Aminian, MD: collaborator

Study Sites (1)

Cleveland Clinic Main Campus

Cleveland, Ohio, 44195, United States

RECRUITING

MeSH Terms

Conditions

Obesity, Morbid; Weight Loss

Interventions

Portasystemic Shunt, Transjugular Intrahepatic; Topiramate; Phentermine; Glucagon-Like Peptide-1 Receptor Agonists; Diet Therapy

Condition Hierarchy (Ancestors)

Obesity; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Body Weight Changes

Intervention Hierarchy (Ancestors)

Portasystemic Shunt, Surgical; Anastomosis, Surgical; Surgical Procedures, Operative; Vascular Grafting; Vascular Surgical Procedures; Cardiovascular Surgical Procedures; Fructose; Hexoses; Monosaccharides; Sugars; Carbohydrates; Ketoses; Amphetamines; Phenethylamines; Ethylamines; Amines; Organic Chemicals; Hypoglycemic Agents; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Nutrition Therapy; Therapeutics

Study Officials

• Sobia Laique, MD

  The Cleveland Clinic

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Awwab F Hammad, MD

CONTACT

+1 216 444 5022; hammada4@ccf.org

Erlind Allkushi

CONTACT

ALLKUSE2@ccf.org

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Model Details: Two-arm randomized controlled trial (1:1) comparing pre-operative TIPS followed by sleeve gastrectomy (TIPS + SG) versus best-option medical weight management in adults (BMI ≥ 35-70 kg/m²) with compensated cirrhosis and clinically significant portal hypertension.

Study Record Dates

• First Submitted: June 27, 2025
• First Posted: July 10, 2025
• Study Start: December 17, 2025
• Primary Completion (Estimated): February 1, 2029
• Study Completion (Estimated): February 1, 2034
• Last Updated: December 23, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)