Body Composition Changes After TIPS and Associated Clinical Outcomes

NCT ID: NCT05420753

Last Updated: 2023-11-07

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 22 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-05-01
• Study Completion Date: 2025-12-31

Brief Summary

The purpose of this study is to prospectively assess the impact of TIPS creation on muscle mass and physical function in patients with cirrhosis, and to determine whether these changes correlate with improved outcomes in patients awaiting liver transplantation. Retrospective observational studies have shown improvement in muscle mass and body composition in cirrhotic patients undergoing TIPS. The investigators aim to now prospectively study this through a pilot randomized controlled trial tracking patients managed with TIPS creation compared to those managed without TIPS to determine whether these observational findings can be seen in a randomized cohort. The investigators hypothesize that TIPS creation will lead to improved muscle mass, body composition and muscle function within the first 12 months after the procedure compared to a control group without TIPS, and that these changes will improve liver disease outcomes in patients awaiting liver transplantation.

Detailed Description

Sarcopenia (loss of muscle mass) and frailty (loss of muscle function) have increasingly become recognized as major prognostic factors in predicting morbidity and mortality with several disease states, including cirrhosis. Cirrhosis represents end-stage liver disease and is complicated by a multitude of clinical sequelae, such as variceal hemorrhage, ascites, renal insufficiency, hepatic encephalopathy, hepatopulmonary syndrome, cardiac dysfunction, infection and hepatocellular carcinoma. To date, liver transplantation remains the only prospect for a curative treatment. As the liver is the primary metabolic organ, sarcopenia is prevalent in cirrhosis, afflicting 30-70% of patients. Observational studies have implicated sarcopenia as an independent risk factor for morbidity and mortality in all clinical sequelae of cirrhosis. Moreover, sarcopenia and frailty have been shown to increase morbidity and mortality of transplant eligible patients on the liver transplant waitlist, as well as mortality of patients after liver transplant. Given the prevalence of sarcopenia and frailty in this patient population, and the severe clinical impacts, addressing these adverse predictors may have profound implications for the outcomes of patients with cirrhosis.

Cirrhosis often leads to portal hypertension, complications of which include lower extremity edema, ascites, hepatic hydrothorax, variceal bleeding, portal hypertensive gastropathy, portal vein thrombosis, and hepatic encephalopathy. Patients with cirrhosis and complications of portal hypertension are currently managed in several ways in clinical practice:

• medical management, including diuretics and non-selective beta blocker therapy
• endoscopic options include variceal banding or glue embolization
• invasive options include large-volume paracentesis (LVP) or transjugular intrahepatic portosystemic shunt (TIPS) creation.

Since 1988, the Liver Transplant Program at OHSU has been successfully treating waitlisted cirrhotic patients with complications of portal hypertension using a combination of these therapies. TIPS creation, particularly in the current era of stent grafts with a dedicated device for this procedure, has been a part of managing patients with cirrhosis as a bridge to transplant for two decades. Depending on the indication, patients can be treated with a combination of these therapies often with significant overlap. For example, a given patient with portal hypertension and ascites may be managed with diuretics and serial LVP vs. TIPS creation, and a given patient with variceal bleeding may be treated with beta-blockers and endoscopic banding vs. TIPS creation.

Of relevance to the proposed trial, recent observational studies have demonstrated significant reversal of sarcopenia after TIPS creation, and this reversal has been strongly correlated with improved survival and less hepatic encephalopathy. Moreover, the time course of muscle gains has been observed to occur within the first 6 months of TIPS creation, critical for patients awaiting liver transplantation, as benefits would occur during typical transplant waitlist time periods. Thus, TIPS creation may represent a major unmet need to address sarcopenia and frailty in patients with cirrhosis, and represents an intervention with potential to reverse this debilitating condition and improve clinical outcomes. Putative mechanisms for how TIPS creation may improve body composition include decreased congestive enteropathy resulting in improved gut nutrient absorption, decrease in metabolic burden from a hyperdynamic cardiopulmonary status in the setting of fluid overload, improvement in renal function, and changes in the gut microbiome resulting in conversion from a catabolic to an anabolic state. A major gap in knowledge, however, remains whether TIPS creation can directly reverse muscle loss. Furthermore, whether reversal of muscle loss results in improved measures of strength, physical performance and clinical outcomes has not been prospectively studied. In this proposal, the investigators plan to address this major knowledge gap through a pilot prospective randomized controlled trial tracking patients managed with TIPS creation compared to those managed without TIPS to determine whether these observational findings can be seen in a randomized cohort.

Conditions

Cirrhosis, Liver; Sarcopenia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

TIPS

Patients in this arm will undergo TIPS creation in addition to their current management.

Group Type: EXPERIMENTAL

Transjugular Intrahepatic Portosystemic Shunt (TIPS) creation

Intervention Type: PROCEDURE

During a TIPS procedure, the interventional radiologist, with the help of x-ray and ultrasound guidance, makes a channel through the liver to connect the portal vein (the vein that carries blood from the digestive organs to the liver) to one of the hepatic vein (three veins that carry blood away from the liver back to the heart) using a special type of needle. The interventional radiologist then replaces the needle with a wire and catheter, and a small tubular device called a stent graft is placed in this channel to keep the pathway open between the two blood vessels.

Standard of care

Patients in this arm will continue to be treated with their current management

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Transjugular Intrahepatic Portosystemic Shunt (TIPS) creation

During a TIPS procedure, the interventional radiologist, with the help of x-ray and ultrasound guidance, makes a channel through the liver to connect the portal vein (the vein that carries blood from the digestive organs to the liver) to one of the hepatic vein (three veins that carry blood away from the liver back to the heart) using a special type of needle. The interventional radiologist then replaces the needle with a wire and catheter, and a small tubular device called a stent graft is placed in this channel to keep the pathway open between the two blood vessels.

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• Patients >18 <99 with cirrhosis wait listed for liver transplantation
• Evidence of complications of portal hypertension:
• Ascites or hydrothorax requiring escalation of diuretic medication
• Persistent ascites or hydrothorax despite diuretic use, or intolerance of diuretic use
• Gastrointestinal varices and blood loss anemia or history of variceal hemorrhage
• Portal hypertensive gastropathy and blood loss anemia
• Chronic portal vein thrombosis requiring recanalization and TIPS for transplant

Exclusion Criteria

• Hepatocellular carcinoma or other active malignancy
• Recurrent overt hepatic encephalopathy
• Uncontrolled coagulopathy with maximum amplitude (MA) <30 on thromboelastography
• Bacteremia or sepsis
• MELD > 25
• Pregnant
• Decisionally impaired individuals
• Need for emergency TIPS creation
• Patients who do not have acceptable alternatives to TIPS creation to manage their disease

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Oregon Health and Science University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Oregon Health and Science University

Portland, Oregon, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Khashayar Farsad, MD

Role: CONTACT

farsad@ohsu.edu

503-494-7660

Lori Russell, RN

Role: CONTACT

watsonlo@ohsu.edu

503-494-7660

Facility Contacts

Khashayar Farsad, MD

Role: primary

farsad@ohsu.edu

503-494-7660

Lori Russell, RN

Role: backup

watsonlo@ohsu.edu

503-494-7660

Other Identifiers

STUDY00022853

Identifier Type: -

Identifier Source: org_study_id