Metabolic Surgery and TIPS for Liver Cirrhosis

(OPTIMAL Trial)

Overseen By Erlind Allkushi

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: The Cleveland Clinic

Disqualifiers: Prior bariatric surgery, Transplant, Severe cardiac, Severe psychiatric, Alcohol abuse, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 5

70 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether combining two procedures can improve health in people with liver cirrhosis and severe obesity. The procedures are TIPS, which lowers liver blood pressure, and sleeve gastrectomy, a weight-loss surgery. Researchers will compare these against standard medical weight management to determine if the combination improves quality of life and promotes greater weight loss. The trial targets individuals with severe obesity and cirrhosis who have increased liver pressure but no severe liver complications, such as abdominal fluid or recent liver failure. Participants will be monitored for health and potential treatment complications. As a Phase 4 trial, this research involves FDA-approved treatments that have proven effective, aiming to understand how they can benefit more patients.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it does allow for the use of current or prior anti-obesity medications.

What is the safety track record for these treatments?

Previous studies have combined sleeve gastrectomy and TIPS in patients with liver disease. One study found that serious problems were rare, with only 1.6% of patients experiencing a major issue like a stomach leak. Another report noted that about 5% of patients developed blood clots in a vein near the liver, which, while concerning, is uncommon.

These procedures have been studied to help manage liver problems and obesity. Although some risks exist, they are generally considered manageable. This means that while side effects may occur, the treatment is usually well-tolerated according to current research.

Discussing potential risks and benefits with a healthcare provider is crucial before deciding to join a clinical trial. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about the combination of TIPS and sleeve gastrectomy for liver cirrhosis because it offers a dual approach that isn't typical in current treatment options. Most treatments focus separately on managing portal hypertension or addressing obesity, but this approach tackles both issues together. The TIPS procedure helps reduce portal pressure, while the sleeve gastrectomy aids in substantial weight loss, which might improve liver function and overall health. On the other hand, the medical weight management program offers a personalized and comprehensive strategy, incorporating lifestyle changes and anti-obesity medications, which can be more adaptable for those who may not qualify for or want surgery. This trial aims to explore how these combined or alternative strategies might offer better outcomes for patients with liver cirrhosis.

What evidence suggests that this trial's treatments could be effective for cirrhosis with CSPH and severe obesity?

This trial will evaluate the effectiveness of combining TIPS and sleeve gastrectomy for individuals with liver disease and severe obesity. Studies have shown that TIPS can reduce pressure in the liver's veins, helping to prevent issues like internal bleeding. Sleeve gastrectomy often results in significant weight loss and improvements in health conditions such as diabetes. Early findings suggest that performing both procedures together could lead to better health outcomes than managing weight with medication, which is another treatment arm in this trial. Additionally, patients who underwent similar treatments in the past experienced manageable risks and complications. Overall, this combined approach offers a promising treatment option for those facing this challenging health condition. ^{1 2 3 5 6}

Who Is on the Research Team?

Sobia Laique, MD

Principal Investigator

The Cleveland Clinic

Are You a Good Fit for This Trial?

This trial is for adults aged 18-70 with severe obesity and liver cirrhosis who have clinically significant portal hypertension but not decompensated liver disease. They must be eligible for sleeve gastrectomy, able to consent, follow study procedures, and have insurance covering the surgery. Exclusions include pregnancy, recent malignancy or organ transplant, severe psychiatric issues or substance abuse, certain blood disorders, and planned relocations.

Inclusion Criteria

BMI 35-70 kg/m² at first study visit

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

My insurance covers metabolic surgery.

Exclusion Criteria

Pregnant, breastfeeding, planning pregnancy, or not using adequate contraception

Investigational therapy within 3 months

I haven't had cancer (other than non-melanoma skin cancer) in the last year.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

TIPS Procedure

Participants undergo transjugular intrahepatic portosystemic shunt (TIPS) placement to reduce portal pressure

1 day

1 visit (in-person)

Interval Metabolic Surgery

Participants receive sleeve gastrectomy approximately 4 to 6 weeks after TIPS placement

4-6 weeks

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments at 1, 3, and 6 months

6 months

3 visits (in-person)

Long-term Follow-up

Some participants may be followed for a longer period to assess long-term outcomes

What Are the Treatments Tested in This Trial?

Interventions

• Sleeve Gastrectomy
• Transjugular Intrahepatic Portosystemic Shunt (TIPS)

Trial Overview The OPTIMAL Trial compares two treatments: one group receives TIPS (a procedure reducing liver pressure) followed by sleeve gastrectomy (weight loss surgery), while the other gets medical weight management including diet and lifestyle changes. The goal is to see if combining TIPS with surgery improves quality of life more than non-surgical care.

How Is the Trial Designed?

Group I: TIPS + Sleeve Gastrectomy Experimental Treatment 3 Interventions

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.

Group II: Best-Option Medical Weight Management Active Control 2 Interventions

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).

Who Is Running the Clinical Trial?

The Cleveland Clinic

Lead Sponsor

Trials

1,072

Recruited

1,377,000+

Ali Aminian, MD

Collaborator

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39739182/

A Bridge to Bariatric Surgery in Morbidly Obese Patients ... We evaluated the impact of pre-operative transjugular intrahepatic portosystemic shunt (TIPS) on the outcomes of bariatric surgery in cirrhosis.

2. journals.lww.com journals.lww.com/international-journal-of-surgery/fulltext/2024/06000/outcomes_of_bariatric_surgery_in_the_setting_of.44.aspx

Outcomes of bariatric surgery in the setting of compensated ... One patient (1.6%) experienced gastric leakage and mortality. There were three (5%) reported cases of portal vein thrombosis, two (3%) postoperative acute renal ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT07058155

NCT07058155 | Optimizing Portal Hypertension With TIPS ... This trial will generate the first prospective data evaluating whether a combined approach of portal pressure reduction and metabolic surgery can safely and ...

4. gi.org gi.org/journals-publications/ebgi/sierra_duong_sep2025/

Surgery in cirrhosis: Strategies for risk stratification and ... Outcomes: The outcomes emphasized in this guideline were: perioperative mortality (particularly 90-day), postoperative hepatic decompensation ( ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6535047/

Outcomes of Sleeve Gastrectomy in Obese Liver ... First, SG has been shown to require less operative time and confers lower perioperative risks when compared with Roux-en-Y gastric bypass. Second, SG does not ...

6. wjgnet.com wjgnet.com/1007-9327/full/v24/i28/3112.htm

Considerations for bariatric surgery in patients with cirrhosis Early studies report an overall 30% postoperative mortality and 11.6% thirty day post-operative mortality after various surgical procedures[8].