Recruiting

TIPS & SG

Sponsor:

The Cleveland Clinic

Code:

NCT07058155

Conditions

Liver Cirrhoses

Portal Hypertension Related to Cirrhosis

Severe Obesity

TIPS

Eligibility Criteria

Sex: All

Age: 18 - 70

Healthy Volunteers: Not accepted

Interventions

Transjugular Intrahepatic Portosystemic Shunt (TIPS)

Sleeve Gastrectomy

Anti-Obesity Pharmacotherapy (Class Effect)

Lifestyle Counseling - Diet & Physical-Activity Program

Study Details

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. 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.

Conditions

Liver Cirrhoses

Portal Hypertension Related to Cirrhosis

Severe Obesity

TIPS

Study ID

NCT07058155

Start date

Dec 17, 2025

Status verified date

Dec, 2025

Completion date

Feb 1, 2034

Anticipated

Primary completion date

Feb 1, 2029

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 70

Healthy Volunteers: Not accepted

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.

Study Design

Enrollment

70 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

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).

Interventions

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.

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.

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.

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.

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 and Locations

Central contacts

Awwab F Hammad, MD

+1 216 444 5022hammada4@ccf.org

Erlind Allkushi

ALLKUSE2@ccf.org

Locations

Cleveland Clinic Main Campus

Recruiting

Cleveland, Ohio, United States, 44195

Contacts

Awwab F Hammad, MD

+1 216 444 5022hammada4@ccf.org

Erlind Allkushi

ALLKUSE2@ccf.org

Principal Investigator:

Sobia Laique, MD

More Information

Sponsor

The Cleveland Clinic

Last update posted

Dec 23, 2025

Last verified

Dec, 2025

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

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by The Cleveland Clinic on 2025-12-23.