Clinical trial NCT05740358: Liver Cirrhosis Network Cohort Study
Official title: Liver Cirrhosis Network Cohort Study
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: 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
Autoimmune Hepatitis
Keywords: Cirrhosis
Liver
Nonalcoholic Fatty Liver Disease
NASH
Nonalcoholic steatohepatitis
Lead sponsor: Northwestern University
Sponsor class: OTHER
Collaborators: name: The Cleveland Clinic
name: Columbia University
name: Weill Medical College of Cornell University
name: Duke University
name: Mayo Clinic
name: University of Miami
name: University of Michigan
name: University of California, San Diego
name: University of California, San Francisco
name: LAC+USC Medical Center
name: Virginia Commonwealth University
name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
name: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
name: National Cancer Institute (NCI)
name: University of Southern California
name: Central Virginia Veterans Healthcare System
First posted: 2023-02-23
Enrollment: 1200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study will include participants with cirrhosis of the liver.

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.


Eligibility criteria: 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 5. \>5 years METAVIR stage 4 fibrosis or Ishak stage 5-6

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 (including trace ascites discovered at screening not requiring intervention), hepatic encephalopathy or variceal bleeding. If a patient has had a history of decompensation, they must have been off any medications to treat decompensation for at least 365 days. Refer to the MOP for clarifying details on evaluating eligibility for patients with a history of prior decompensation.
* 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) \> 2X upper limit of normal (ULN) within 90 days prior to consent or during Screening\*
* In patients living with HIV: CD4+ T cell count less than 100 cells/mm3 within 90 days prior to consent or during Screening\*

  * Indicates an exclusion criterion that may depend on laboratory results and other clinical assessments to be ordered during Screening after confirming the participant is otherwise eligible. If the test was performed as standard-of-care in the 90 days prior to consent, it does not need to be re-done for eligibility.

Primary outcomes:
measure: Time-to-decompensation
timeFrame: 3 years
Secondary outcomes:
measure: Number of decompensations
timeFrame: 3 years
measure: All-cause mortality
timeFrame: 3 years
measure: Adjudicated liver-related mortality
timeFrame: 3 years
measure: All-cause hospitalizations
timeFrame: 3 years
measure: Number of liver-related hospitalizations
timeFrame: 3 years
measure: Time to liver transplantation
timeFrame: 3 years
measure: Time to development of hepatocellular carcinoma (HCC)
timeFrame: 3 years
measure: Time to development of portal and/or mesenteric vein thrombosis
timeFrame: 3 years
measure: Change in liver stiffness as measured by vibration-controlled transient elastography (VCTE)
timeFrame: 3 years
measure: Degree of fibrosis as measured by fibrosis-4 index (FIB-4)
timeFrame: 3 years
measure: Overall physical health and overall mental health as measured by Patient Reported Outcomes Measurement Information System (PROMIS-29+2 profile v2.1)
timeFrame: 3 years
measure: Change in cognitive function as measured by Stroop Test
timeFrame: 3 years
measure: Change in frailty as measured by the Liver Frailty Index
timeFrame: 3 years
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: University of California San Diego NAFLD Research Center
state: California
city: Los Angeles
country: United States
facility: Keck Medical Center of USC
state: California
city: Los Angeles
country: United States
facility: LAC + USC Medical Center
state: California
city: San Francisco
country: United States
facility: UCSF/Zuckerberg San Francisco General Hospital and Trauma Center
state: California
city: San Francisco
country: United States
facility: UCSF Medical Center
state: California
city: Miami
country: United States
facility: University of Miami Health System
state: Florida
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: New York
country: United States
facility: New York Presbyterian/Weill Cornell
state: New York
city: New York
country: United States
facility: Columbia University Iriving School of Medicine
state: New York
city: Durham
country: United States
facility: Duke Liver Center
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Richmond
country: United States
facility: Central Virginia Veterans Healthcare System
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
Study officials:
affiliation: Northwestern University
name: Jody Ciolino
role: PRINCIPAL_INVESTIGATOR
References: