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

NCT03178630 | Recruiting

• 1 other identifier: CIN002 MRI biomarkers in AILD
• Study Type: observational
• Target: 150
• Locations: 1 country
• Sites: 1

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.

Conditions

Autoimmune Liver Disease; Autoimmune Hepatitis; Primary Sclerosing Cholangitis

Outcome Measures

Primary Outcomes (9)

• 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 Outcomes (4)

• Changes in liver/spleen volumes

  24 months

• Changes in T1rho, T1 and T2 mapping

  24 months

• Clinical endpoints of AILD: Pruritus

  120 months

• Clinical endpoints of AILD

  120 months

Study Arms (1)

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.

Eligibility Criteria

• Age: 6 Years - 23 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• 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.

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Children's Hospital Medical Center, Cincinnati: lead

Study Sites (1)

Cincinnati Children's Hospital and Medical Center

Cincinnati, Ohio, 45229, United States

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Plasma and serum samples.

MeSH Terms

Conditions

Hepatitis, Autoimmune; Cholangitis, Sclerosing

Condition Hierarchy (Ancestors)

Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Autoimmune Diseases; Immune System Diseases; Cholangitis; Bile Duct Diseases; Biliary Tract Diseases

Study Officials

• Alexander Miethke, MD

  Cincinnati Childrens Hospital Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Alexander Miethke, MD

CONTACT

513-636-8948; alexander.miethke@cchmc.org

Cyd Castro Rojas, PhD

CONTACT

513-517-0580; cyd.castrorojas@cchmc.org

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 30, 2017
• First Posted: June 7, 2017
• Study Start: February 20, 2017
• Primary Completion (Estimated): February 1, 2030
• Study Completion (Estimated): February 1, 2031
• Last Updated: December 12, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)