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

Recruiting

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

• Registration Number: NCT03178630
• Lead Sponsor: Children's Hospital Medical Center, Cincinnati

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2017-02-20
• Study First Submitted: 2017-03-30
• Study First Submitted QC: 2017-06-06
• Study First Posted: 2017-06-07
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-09
• Last Update Posted: 2024-12-12
• Primary Completion: 2030-02
• Study Completion: 2031-02

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 150

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
long-term clinical outcomes: survival with the native liver	120 months	Annual assessment of survival with the native liver (Yes=1, No=0) will be done within 10 years of follow-up.
long-term clinical outcomes: ascites	120 months	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.
Mean shear stiffness of the liver	24 months	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).
long-term clinical outcomes: hospital admissions for cholangitis	120 months	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.
long-term clinical outcomes:diagnosis of cholangiocarcinoma	120 months	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.
long-term clinical outcomes: variceal bleeding	120 months	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.
Change of intrahepatic bile duct irregularities between V0 (baseline visit) and V1 (visit after12 months) or V2 (visit after 24 months).	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).
Change of extra-hepatic duct irregularities between V0 (baseline visit) and V1 (visit after 12 months) or V2 (visit after 24 months).	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).
long-term clinical outcomes:endoscopic interventions for biliary strictures	120 months	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.

Secondary Outcome Measures

Name	Time	Method
Changes in T1rho, T1 and T2 mapping	24 months	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.
Changes in liver/spleen volumes	24 months	Changes in liver/spleen volumes (mL) between V0 (baseline visit) and V1 (visit after 12 months) or V2 (visit after 24 months).
Clinical endpoints of AILD	120 months	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.
Clinical endpoints of AILD: Pruritus	120 months	Annual assessment for Pruritus (on visual analogue scale of 0-10) will be done within 10 years of follow-up.

Trial Locations

Locations (1)

Cincinnati Children's Hospital and Medical Center; 🇺🇸 Cincinnati, Ohio, United States