Liver Cirrhosis Network Cohort Study

Cirrhosis Clinical Trial

— LCN-C  

Official title:

Liver Cirrhosis Network Cohort Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05740358
• Other study ID #: LCN Cohort Study
• Secondary ID: 1U24DK130164-01P
• Status: Recruiting
• Start date: November 14, 2022
• Est. completion date: September 1, 2028

Study information

• Verified date: January 2024
• Source: Northwestern University
• Contact: Crystal K Santillanes, MS
• Phone: 312-503-5536
• Email: lcn[@]northwestern.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Liver Cirrhosis Network (LCN) Cohort Study is an observational study designed to identify risk factors and develop prediction models for risk of decompensation in adults with liver cirrhosis. LCN Cohort Study involves multiple institutions and an anticipated 1200 participants. Enrolled participants will have study visits every 6 months (180 days), with opportunities to complete specific visit components via telehealth or remotely. Visits will include collection of questionnaire data and the in-person visits will include questionnaires, physical exams, imaging, and sample collection.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1200
• Est. completion date: September 1, 2028
• Est. primary completion date: September 1, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age = 18 years

• Willing to provide samples at baseline

• Cirrhosis

Where Cirrhosis is defined as:

1. At least one liver biopsy within 5 years prior to consent showing either: a) Metavir stage 4 fibrosis; Ishak Stage 5-6 fibrosis OR

2. At least 2 of the following:

1. Evidence on imaging: Nodular liver with either splenomegaly or recanalized umbilical vein within the past year 2. Liver stiffness: VCTE within one year prior to consent or during Screening =12.5 kPa or MRE within one year prior to consent or during Screening =5 kPa 3. Evidence of varices demonstrated on imaging or endoscopy within 3 years prior to consent or during Screening 4. Either: FIB-4>2.67 or platelets <150/mL within 6 months prior to consent or during Screening

Exclusion Criteria:

• Known and documented prior or current hepatocellular carcinoma (HCC) or cholangiocarcinoma

• Known transjugular intrahepatic portosystemic shunt (TIPS), balloon retrograde transvenous obliteration (BRTO) or porto-systemic shunt surgery regardless of time of occurrence

• Known prior solid organ transplant or bone marrow transplant

• Current participation in active medication treatment trials at the time of consent for LCN Cohort Study

• Prisoners or individuals with more than 180 days incarceration pending due to difficulty with visits

• Bariatric surgery in the last 180 days prior to consent

• Known history of fontan procedure-associated liver disease (FALD)

• Known current medical or psychiatric conditions which, in the opinion of the investigator, would make the participant unsuitable for the study or interfere with or prevent follow-up per protocol

• Current liver-unrelated end-stage organ failures (Dialysis, stage 3-4 congestive heart failure (CHF), current chronic obstructive pulmonary disease (COPD) on home oxygen, current known active malignancy besides non-melanomatous skin cancer or carcinoma in situ)

• Documented history of acute alcohol-associated hepatitis (according to NIAAA criteria as described in the MOP) in the 180 days prior to consent

• Documented current or continued signs and symptoms of acute Wilson disease (acute liver failure, acute neurological deficits, hemolysis)

• In patients with primary sclerosing cholangitis (PSC): Current active cholangitis with 90 days prior to consent

• Documented cardiac cirrhosis

• Known recent (within the last 365 days) or present hepatic decompensation with ascites/hydrothorax, hepatic encephalopathy or variceal bleeding

• Known or documented habitual non-adherence to previous research studies or medical procedures or unwillingness to adhere to protocol (e.g., unwilling to obtain consent or samples)

• Current model for end-stage liver disease (MELD-Na) cut off = 15

• Current Child-Turcotte-Pugh (CTP) B or C

• Current known Hepatitis C Virus (HCV) without sustained virologic response (SVR)

• Current known quantifiable Hepatitis B Virus (HBV) viral DNA on therapy with ongoing adherence on suppressive therapy

• In patients with autoimmune hepatitis: serum aspartate aminotransferase (AST) > 2 times upper limit of normal (ULN) within 60 days prior to consent or during Screening

• In patients living with HIV: cluster of differentiation 4 (CD4) + T cell count less than 100 cells/mm3 within 60 days prior to consent or during Screening

Related Conditions & MeSH terms

• Cholangitis
• Cholangitis, Sclerosing
• Cirrhosis
• Cirrhosis Due to Hepatitis B
• Cirrhosis Due to Hepatitis C
• Cirrhosis, Liver
• Fibrosis
• Hepatitis
• Hepatitis A
• Hepatitis B
• Hepatitis C
• Liver Cirrhosis
• Liver Cirrhosis, Alcoholic
• Liver Cirrhosis, Biliary

Locations

Country	Name	City	State
United States	University of Michigan	Ann Arbor	Michigan
United States	Cleveland Clinic	Cleveland	Ohio
United States	Duke Liver Center	Durham	North Carolina
United States	University of California San Diego NAFLD Research Center	La Jolla	California
United States	Keck Medical Center of USC	Los Angeles	California
United States	LAC + USC Medical Center	Los Angeles	California
United States	University of Miami Health System	Miami	Florida
United States	Columbia University Iriving School of Medicine	New York	New York
United States	New York Presbyterian/Weill Cornell	New York	New York
United States	Central Virginia Veterans Healthcare System	Richmond	Virginia
United States	Virginia Commonwealth University	Richmond	Virginia
United States	Mayo Clinic	Rochester	Minnesota
United States	UCSF Medical Center	San Francisco	California
United States	UCSF/Zuckerberg San Francisco General Hospital and Trauma Center	San Francisco	California

Sponsors (17)

Lead Sponsor

Collaborator

Northwestern University

Central Virginia Veterans Healthcare System, Columbia University, Duke University, LAC+USC Medical Center, Mayo Clinic, National Cancer Institute (NCI), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institute on Alcohol Abuse and Alcoholism (NIAAA), The Cleveland Clinic, University of California, San Diego, University of California, San Francisco, University of Miami, University of Michigan, University of Southern California, Virginia Commonwealth University, Weill Medical College of Cornell University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time-to-decompensation	Time-to-decompensation, defined as any of the following events: Ascites: Grade 2 or 3; Hepatic Encephalopathy (HE) (i.e., an episode of overt HE); Portal hypertensive upper gastrointestinal (GI) bleeding	3 years
Secondary	Number of decompensations	Number of decompensations (treated as a count variable in analyses)	3 years
Secondary	All-cause mortality	All-cause mortality (treated as time-to-event in analyses)	3 years
Secondary	Adjudicated liver-related mortality (treated as time-to-event in analyses)	Adjudicated liver-related mortality (treated as time-to-event in analyses)	3 years
Secondary	All-cause hospitalizations	All-cause hospitalizations (treated as a count variable in analyses)	3 years
Secondary	Number of liver-related hospitalizations	Liver-related hospitalizations (treated as a count variable in analyses)	3 years
Secondary	Time to liver transplantation	Liver transplantation (treated as time-to-event in analyses)	3 years
Secondary	Time to development of hepatocellular carcinoma (HCC)	Development of HCC (treated as time-to-event in analyses)	3 years
Secondary	Time to development of portal and/or mesenteric vein thrombosis	Development of portal and/or mesenteric vein thrombosis (treated as time-to-event in analyses)	3 years
Secondary	Major adverse cardiac events (MACE)	MACE (treated as time-to-event in analyses)	3 years
Secondary	Change in liver stiffness as measured by vibration-controlled transient elastography (VCTE)	Liver stiffness as measured by VCTE (treated as continuous measure in analyses)	3 years
Secondary	Degree of fibrosis as measured by fibrosis-4 index (FIB-4)	Degree of fibrosis as measured by FIB-4 (treated as continuous measure in analyses)	3 years
Secondary	Overall physical health and overall mental health as measured by Patient Reported Outcomes Measurement Information System (PROMIS-29+2 profile v2.1)	Overall physical health and overall mental health as measured by Patient Reported Outcomes Measurement Information System (PROMIS-29+2 profile v2.1) relevant "T-scores," a continuous measure. T-scores are normalized to the population and are centered at 50 with anticipated standard deviation of 10. A higher score means better "health."	3 years
Secondary	Change in cognitive function as measured by Stroop Test	Change in cognitive function as measured by Stroop Test (treated as continuous measure in analyses). Measured as time to complete the test. A higher score means longer time to complete, which means more impaired function. Minimum score is 0, and there is no maximum score.	3 years
Secondary	Change in frailty as measured by the Liver Frailty Index	Change in frailty as measured by the Liver Frailty Index (treated as continuous measure in analyses). A higher score means the participant is more frail. The score is based on grip strength, number of chair stands per second, and balance time. https://liverfrailtyindex.ucsf.edu/ Maximum score of 6, and there is no minimum score.	3 years

External Links

•   Information about the study