MRI Biomarkers in as Predictor of Clinical Endpoints in Pediatric Autoimmune Liver Disease

Longitudinal Study for the Assessment of MRI Based Biomarkers as a Predictors of Clinical Endpoints in Pediatric Onset Autoimmune Liver Disease

Autoimmune liver diseases (AILD), which include Primary Sclerosing Cholangitis (PSC) and Autoimmune Hepatitis (AIH) are a common etiological factor for chronic liver disease among adolescents. This is a longitudinal study to identify surrogate endpoints with an accurate predictive value for the progression of hepatobiliary damage in subjects with pediatric onset AILD. This study will involve collection of MRI-based data at the time of enrollment and at year 1 and 2 of follow up, and collection of clinical data for 10 years following enrollment. There is a strong possibility that MRI quantitative techniques may be more sensitive to disease progression than standard clinical and laboratory tests. To investigate predictivity of MRI based biomarkers, summary measures of MRCP/MREL from baseline, Year 1 and Year 2, e.g. change rate, maximum, and average will be calculated as predictors for Year 10 clinical outcomes. The same predictors will also be used to model native liver survival in a proportional hazard regression. Findings from this study may be used to assess disease progression and to predict complications and survival of liver disease patients.

Study Overview

• Status: Recruiting
• Conditions: Autoimmune Liver Disease; Primary Sclerosing Cholangitis; Autoimmune Hepatitis

• Study Type: Observational
• Enrollment (Anticipated): 150

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Recruiting
      • Cincinnati Children's Hospital and Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 23 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

A total of 150 patients between 6 and 23 years of age with a diagnosis of PSC or AIH will be enrolled and followed up to 10 Years.

Description

Inclusion Criteria:

1. Age 6-23 years old.
2. Established clinical diagnosis of AIH or PSC.

Exclusion Criteria:

1. History of liver transplantation.
2. Chronic Hepatitis B or untreated hepatitis C virus infection.
3. Pregnancy.
4. Absolute contraindication for MRI (e.g. pacemaker, metallic implants, claustrophobia).
5. Diagnosis of cystic fibrosis or biliary atresia
6. Diagnosis of cardiac hepatopathy.
7. Diagnosis of Wilson's disease, Alpha-1 Antitrypsin deficiency, or Glycogen storage disease.
8. Skin conditions which could be aggravated by MREL (i.e. Epidermolysis bullosa).

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Patients with autoimmune liver disease; Patients with autoimmune liver disease Patients (6-23 y.o.) with established clinical diagnosis of AIH or suspected diagnosis of AIH based on elevated serum AST or ALT, elevated IgG level >1.1 ULN, elevated titer of autoantibodies, including ANA, SMA, LKM, LC-1 or SLA, which is consistent with the simplified criteria for the diagnosis of AIH in children will be enrolled. Patients (6-23 y.o.) with established clinical diagnosis of PSC or Suspected diagnosis of PSC supported by abnormal cholangiogram (ERCP or MRCP) or elevated GGT>1.5 ULN and dilated bile ducts by liver ultrasound will be enrolled.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of intrahepatic bile duct irregularities between V0 (baseline visit) and V1 (visit after12 months) or V2 (visit after 24 months).	Change of intrahepatic bile duct irregularities between V0 and V1 or V2 by MRCP (scored by Majoie classification on 4 point scale of 0-3).	24 months
Change of extra-hepatic duct irregularities between V0 (baseline visit) and V1 (visit after 12 months) or V2 (visit after 24 months).	Change of extra-hepatic duct irregularities between V0 and V1 or V2 by MRCP (scored by Majoie classification on 5 point scale 0-4).	24 months
Mean shear stiffness of the liver	Change in mean shear stiffness (kPa) of the liver by MREL between V0 (baseline visit) and V1 ( visit after 12 months) or V2 (visit after 24 months).	24 months
long-term clinical outcomes: survival with the native liver	Annual assessment of survival with the native liver (Yes=1, No=0) will be done within 10 years of follow-up.	120 months
long-term clinical outcomes: hospital admissions for cholangitis	Annual assessment of long-term clinical outcomes will be done within 10 years of follow-up. Any hospital admissions for cholangitis (Yes=1, No=0) since last visit will be recorded at the time of follow-up.	120 months
long-term clinical outcomes:endoscopic interventions for biliary strictures	Annual assessment of long-term clinical outcomes will be done within 10 years of follow-up. Endoscopic interventions for biliary strictures (Yes=1, No=0) since last visit will be recorded at the time of follow-up.	120 months
long-term clinical outcomes:diagnosis of cholangiocarcinoma	Annual assessment of long-term clinical outcomes will be done within 10 years of follow-up. If there is diagnosis of cholangiocarcinoma (Yes=1, No=0) since last visit will be recorded.	120 months
long-term clinical outcomes: variceal bleeding	Annual assessment of long-term clinical outcomes will be done within 10 years of follow-up. Presence or absence of variceal bleeding (Yes=1, No=0) since last visit will be recorded.	120 months
long-term clinical outcomes: ascites	Annual assessment of long-term clinical outcomes will be done within 10 years of follow-up. Presence or absence of ascites (Yes=1, No=0) since last visit will be recorded.	120 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in liver/spleen volumes	Changes in liver/spleen volumes (mL) between V0 (baseline visit) and V1 (visit after 12 months) or V2 (visit after 24 months).	24 months
Changes in T1rho, T1 and T2 mapping	Readouts of T1rho, T1 and T2 mapping between baseline MRI at V0 (baseline visit) and repeat ones at V1 (after12 months) or V2 (after 24 months) in msec.	24 months
Clinical endpoints of AILD: Pruritus	Annual assessment for Pruritus (on visual analogue scale of 0-10) will be done within 10 years of follow-up.	120 months
Clinical endpoints of AILD	Annual assessment for Clinical diagnosis of hepatopulmonary syndrome (Yes=1, No=0) and/or hepatic encephalopathy (Yes=1, No=0) will be done within 10 years of follow-up.	120 months

Collaborators and Investigators

• Sponsor: Children's Hospital Medical Center, Cincinnati

Study record dates

Study Major Dates

• Study Start (Actual): February 20, 2017
• Primary Completion (Anticipated): February 1, 2030
• Study Completion (Anticipated): February 1, 2031

Study Registration Dates

• First Submitted: March 30, 2017
• First Submitted That Met QC Criteria: June 6, 2017
• First Posted (Actual): June 7, 2017

Study Record Updates

• Last Update Posted (Actual): February 15, 2023
• Last Update Submitted That Met QC Criteria: February 13, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Immune System Diseases; Autoimmune Diseases; Hepatitis, Chronic; Biliary Tract Diseases; Hepatitis; Bile Duct Diseases; Liver Diseases; Cholangitis; Cholangitis, Sclerosing; Hepatitis, Autoimmune
• Other Study ID Numbers: CIN002 MRI biomarkers in AILD

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No