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Trial record 8 of 688 for:    Alexander Disease

MRI Based Biomarkers in Pediatric Autoimmune Liver Disease

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ClinicalTrials.gov Identifier: NCT03175471
Recruitment Status : Recruiting
First Posted : June 5, 2017
Last Update Posted : June 5, 2017
Sponsor:
Information provided by (Responsible Party):
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 factors for chronic liver disease among adolescents. In all these conditions, autoimmune lymphocyte responses are thought to orchestrate inflammatory injury against hepatocytes (primarily in AIH) or cholangiocytes (in PSC). In this proposal we aim to evaluate the Magnetic Resonance Imaging (MRI) modalities; MR cholangiopancreatography (MRCP) and MR elastography (MREL), as non-invasive biomarkers to assess two primary pathophysiological processes of AILD: bile duct damage and liver fibrosis. In this cross-sectional study MRI based findings of bile duct injury and liver fibrosis will be correlated with both liver histology and circulating biomarkers of these disease processes.

Condition or disease
Autoimmune Liver Disease Primary Sclerosing Cholangitis Autoimmune Hepatitis

Study Type : Observational
Estimated Enrollment : 115 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Cross-sectional Study for Assessment of MRI Based Biomarkers of Bile Duct Injury and Hepatic Fibrosis in Pediatric Onset Autoimmune Liver Disease
Actual Study Start Date : January 17, 2017
Estimated Primary Completion Date : January 2020
Estimated Study Completion Date : January 2021


Group/Cohort
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.




Primary Outcome Measures :
  1. MRI based outcomes [ Time Frame: 36 months ]

    MRCP based assessment of intrahepatic and extrahepatic duct irregularities by Majoie classification (on 4 and 5 point scale of 0-3 and 0-4 respectively; 0: No visible abnormalities, 1: minimal dilatation/irregularities, 2: saccular dilatations/segmental stricture, 3: severe pruning, 4: Extremely irregular margin).

    MREL based quantification of mean shear stiffness (kPa) of liver.


  2. Liver histopathology based assessment of bile duct injury by ISHAK Score [ Time Frame: 36 months ]
    Assessment of bile duct injury by ISHAK Score (Confluent necrosis: on the 7 point scale of 0-6; Focal necrosis on the 4 point scale of 0-4 and portal inflammation on the 4 point scale of 0-4).

  3. Liver histopathology based assessment of bile duct injury by Ludwig score [ Time Frame: 36 months ]
    Assessment of bile duct injury by Ludwig score (on five point scale of 0-4; 0: No ductal injury, 1: portal inflammation, 2: periportal inflammation, 3: Portal bridging, 4: Nodular cirrhosis).

  4. Liver histopathology based assessment of liver fibrosis by Nakanuma score [ Time Frame: 36 months ]
    Assessment of liver fibrosis by Nakanuma score for on the 4 point scale of 0-3 (0; No portal fibrosis, 1; Portal fibrosis; 2; Bridging fibrosis, 3; Liver cirrhosis) .

  5. Liver histopathology based assessment of liver fibrosis by Ishak score [ Time Frame: 36 months ]
    Assessment of liver fibrosis by Ishak score on the 7 point scale of 0-6 (0; Absent, 1; confluent necrosis, 2; necrosis in some areas, 3; necrosis in most areas, 4; necrosis with occasional portal-central bridging necrosis, 5; necrosis with multiple portal-central bridging necrosis, 6; Panacinar or multiacinar necrosis).

  6. Liver histopathology based assessment of cholangitis and hepatic activity [ Time Frame: 36 months ]
    Cholangitis and hepatic activity by Nakanuma score for on the 4 point scale of 0-3 (0; No bile duct loss, 1; Bile duct loss in <1/3 of portal tracts; 2; Bile duct loss in 1/3-2/3 of portal tracts, 3; Bile duct loss in >2/3 of portal tracts).

  7. Serum based outcome [ Time Frame: 36 months ]
    Quantification of serum alkaline phosphatase (ALP in U/L) and Gamma-glutamyl transpeptidase (GGT in U/L).

  8. Enhanced Liver Fibrosis (ELF) score [ Time Frame: 36 months ]
    Assesment of Enhanced Liver Fibrosis (ELF) score on continuous scale of 1-10; <7.7 none -mild. ≥7.7 -<9.8 moderate, >9.8 sever).


Secondary Outcome Measures :
  1. MR T1rho, T1, T2 Imaging [ Time Frame: 36 Months ]
    Mean of MR T1rho, T1, T2 signal in msec to measure the inflammation.

  2. Liver Morphometry [ Time Frame: 36 Months ]
    Collagen deposition in percent area fibrosis by image analysis

  3. Liver histopathology based outcomes [ Time Frame: 36 Months ]
    Liver histopathology based grade of inflammation by Scheuer score on 5 point scale of 0-4; (0: No ductal injury, 1: portal inflammation, 2: periportal inflammation, 3: Portal to portal bridging, 4: Nodular cirrhosis).

  4. Serum based outcomes [ Time Frame: 36 Months ]
    Quantification of serum fractionated ALP (U/L)

  5. Serum MMP7 [ Time Frame: 36 Months ]
    Quantification of serum MMP7 (pg/mL)


Biospecimen Retention:   Samples With DNA
Plasma and serum samples, Liver biopsy tissue samples


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Ages Eligible for Study:   6 Years to 23 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
A total of 115 patients between 6 and 23 years of age with a diagnosis of PSC or AIH will be enrolled.
Criteria

Inclusion Criteria:

  1. Age 6-23 years old.
  2. Established or suspected 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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03175471


Contacts
Contact: Alexander Miethke, MD 513-636-8948 alexander.miethke@cchmc.org
Contact: Ruchi Singh, PhD 513-517-0580 ruchi.singh@cchmc.org

Locations
United States, Ohio
Cincinnati Childrens Hospital Medical Center Recruiting
Cincinnati, Ohio, United States, 45229
Contact: Alexander Miethke, MD    513-636-5581    alexander.miethke@cchmc.org   
Principal Investigator: Alexander Miethke, MD         
Sponsors and Collaborators
Children's Hospital Medical Center, Cincinnati
Investigators
Principal Investigator: Alexander Miethke, MD Cincinnati Childrens Hospital Medical Center

Responsible Party: Children's Hospital Medical Center, Cincinnati
ClinicalTrials.gov Identifier: NCT03175471     History of Changes
Other Study ID Numbers: CIN001-MRI biomarkers in AILD
First Posted: June 5, 2017    Key Record Dates
Last Update Posted: June 5, 2017
Last Verified: June 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Liver Diseases
Digestive System Diseases
Bile Duct Diseases
Biliary Tract Diseases
Autoimmune Diseases
Immune System Diseases
Cholangitis
Cholangitis, Sclerosing
Hepatitis, Autoimmune
Hepatitis, Chronic
Hepatitis