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Trial record 21 of 29 for:    Recruiting, Not yet recruiting Studies | Primary Sclerosing Cholangitis

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

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ClinicalTrials.gov Identifier: NCT03178630
Recruitment Status : Recruiting
First Posted : June 7, 2017
Last Update Posted : August 23, 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 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.

Condition or disease
Autoimmune Liver Disease Autoimmune Hepatitis Primary Sclerosing Cholangitis

Study Type : Observational
Estimated Enrollment : 115 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Longitudinal Study for the Assessment of MRI Based Biomarkers as a Predictors of Clinical Endpoints in Pediatric Onset Autoimmune Liver Disease
Actual Study Start Date : February 20, 2017
Estimated Primary Completion Date : February 2030
Estimated Study Completion Date : February 2031


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.




Primary Outcome Measures :
  1. Change of intrahepatic bile duct irregularities between V0 (baseline visit) and V1 (visit after12 months) or V2 (visit after 24 months). [ Time Frame: 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).

  2. Change of extra-hepatic duct irregularities between V0 (baseline visit) and V1 (visit after 12 months) or V2 (visit after 24 months). [ Time Frame: 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).

  3. Mean shear stiffness of the liver [ Time Frame: 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).

  4. long-term clinical outcomes: survival with the native liver [ Time Frame: 120 months ]
    Annual assessment of survival with the native liver (Yes=1, No=0) will be done within 10 years of follow-up.

  5. long-term clinical outcomes: hospital admissions for cholangitis [ Time Frame: 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.

  6. long-term clinical outcomes:endoscopic interventions for biliary strictures [ Time Frame: 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.

  7. long-term clinical outcomes:diagnosis of cholangiocarcinoma [ Time Frame: 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.

  8. long-term clinical outcomes: variceal bleeding [ Time Frame: 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.

  9. long-term clinical outcomes: ascites [ Time Frame: 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.


Secondary Outcome Measures :
  1. Changes in liver/spleen volumes [ Time Frame: 24 months ]
    Changes in liver/spleen volumes (mL) between V0 (baseline visit) and V1 (visit after 12 months) or V2 (visit after 24 months).

  2. Changes in T1rho, T1 and T2 mapping [ Time Frame: 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.

  3. Clinical endpoints of AILD: Pruritus [ Time Frame: 120 months ]
    Annual assessment for Pruritus (on visual analogue scale of 0-10) will be done within 10 years of follow-up.

  4. Clinical endpoints of AILD [ Time Frame: 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.


Biospecimen Retention:   Samples With DNA
Plasma and serum samples.


Information from the National Library of Medicine

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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 and followed up to 10 Years.
Criteria

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).

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): NCT03178630


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 Children's Hospital and Medical Center Recruiting
Cincinnati, Ohio, United States, 45229
Contact: Alexander Miethke, MD    513-636-9078    alexander.miethke@cchmc.org   
Contact: Ruchi Singh, PhD    513-517-0580    ruchi.singh@cchmc.org   
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: NCT03178630     History of Changes
Other Study ID Numbers: CIN002 MRI biomarkers in AILD
First Posted: June 7, 2017    Key Record Dates
Last Update Posted: August 23, 2017
Last Verified: August 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:
Cholangitis
Cholangitis, Sclerosing
Liver Diseases
Hepatitis, Autoimmune
Digestive System Diseases
Bile Duct Diseases
Biliary Tract Diseases
Hepatitis, Chronic
Hepatitis
Autoimmune Diseases
Immune System Diseases