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

Primary Sclerosing Cholangitis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03178630
• Other study ID #: CIN002 MRI biomarkers in AILD
• Status: Recruiting
• Start date: February 20, 2017
• Est. completion date: February 2031

Study information

• Verified date: February 2023
• Source: Children's Hospital Medical Center, Cincinnati
• Contact: Alexander Miethke, MD
• Phone: 513-636-8948
• Email: alexander.miethke[@]cchmc.org
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 150
• Est. completion date: February 2031
• Est. primary completion date: February 2030
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years to 23 Years

Eligibility

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).

Related Conditions & MeSH terms

• Autoimmune Hepatitis
• Autoimmune Liver Disease
• Cholangitis
• Cholangitis, Sclerosing
• Hepatitis, Autoimmune
• Liver Diseases
• Primary Sclerosing Cholangitis

Locations

Country	Name	City	State
United States	Cincinnati Children's Hospital and Medical Center	Cincinnati	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Children's Hospital Medical Center, Cincinnati

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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