LCN-C: Liver Cirrhosis Network Cohort Study

Sponsor

Northwestern University (Other)

Overall Status

Recruiting

CT.gov ID

NCT05740358

Collaborator

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

1,200

Enrollment

Locations

69.6

Anticipated Duration (Months)

85.7

Patients Per Site

1.2

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Cirrhosis Cirrhosis, Liver Cirrhosis Early Cirrhosis Due to Hepatitis B Cirrhosis Advanced Cirrhosis Infectious Cirrhosis Alcoholic Cirrhosis, Biliary Cirrhosis Cryptogenic Cirrhosis Due to Hepatitis C Cirrhosis Due to Primary Sclerosing Cholangitis

Study Design

Study Type:

Observational

Anticipated Enrollment :

1200 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Liver Cirrhosis Network Cohort Study

Actual Study Start Date :

Nov 14, 2022

Anticipated Primary Completion Date :

Sep 1, 2027

Anticipated Study Completion Date :

Sep 1, 2028

Outcome Measures

Primary Outcome Measures

Time-to-decompensation [3 years]
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

Secondary Outcome Measures

Number of decompensations [3 years]
Number of decompensations (treated as a count variable in analyses)
All-cause mortality [3 years]
All-cause mortality (treated as time-to-event in analyses)
Adjudicated liver-related mortality (treated as time-to-event in analyses) [3 years]
Adjudicated liver-related mortality (treated as time-to-event in analyses)
All-cause hospitalizations [3 years]
All-cause hospitalizations (treated as a count variable in analyses)
Number of liver-related hospitalizations [3 years]
Liver-related hospitalizations (treated as a count variable in analyses)
Time to liver transplantation [3 years]
Liver transplantation (treated as time-to-event in analyses)
Time to development of hepatocellular carcinoma (HCC) [3 years]
Development of HCC (treated as time-to-event in analyses)
Time to development of portal and/or mesenteric vein thrombosis [3 years]
Development of portal and/or mesenteric vein thrombosis (treated as time-to-event in analyses)
Major adverse cardiac events (MACE) [3 years]
MACE (treated as time-to-event in analyses)
Change in liver stiffness as measured by vibration-controlled transient elastography (VCTE) [3 years]
Liver stiffness as measured by VCTE (treated as continuous measure in analyses)
Degree of fibrosis as measured by fibrosis-4 index (FIB-4) [3 years]
Degree of fibrosis as measured by FIB-4 (treated as continuous measure in analyses)
Overall physical health and overall mental health as measured by Patient Reported Outcomes Measurement Information System (PROMIS-29+2 profile v2.1) [3 years]
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."
Change in cognitive function as measured by Stroop Test [3 years]
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.
Change in frailty as measured by the Liver Frailty Index [3 years]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age ≥ 18 years
Willing to provide samples at baseline
Cirrhosis

Where Cirrhosis is defined as:

At least one liver biopsy within 5 years prior to consent showing either: a) Metavir stage 4 fibrosis; Ishak Stage 5-6 fibrosis OR
If no liver biopsy, the following imaging + laboratory criteria define cirrhosis for the purposes of this protocol:
Evidence on imaging, of stiffness, or of varices according to the MOP, AND 2. Either: FIB-4>2.67 OR platelets <150 (within 180 days 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) 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California San Diego NAFLD Research Center	La Jolla	California	United States	92035
2	Keck Medical Center of USC	Los Angeles	California	United States	90033
3	LAC + USC Medical Center	Los Angeles	California	United States	90033
4	UCSF/Zuckerberg San Francisco General Hospital and Trauma Center	San Francisco	California	United States	94110
5	UCSF Medical Center	San Francisco	California	United States	94143
6	University of Miami Health System	Miami	Florida	United States	33122
7	University of Michigan	Ann Arbor	Michigan	United States	48109
8	Mayo Clinic	Rochester	Minnesota	United States	55901
9	New York Presbyterian/Weill Cornell	New York	New York	United States	10021
10	Columbia University Iriving School of Medicine	New York	New York	United States	10031
11	Duke Liver Center	Durham	North Carolina	United States	27710
12	Cleveland Clinic	Cleveland	Ohio	United States	44192
13	Central Virginia Veterans Healthcare System	Richmond	Virginia	United States	23249
14	Virginia Commonwealth University	Richmond	Virginia	United States	23298