Prediction by Ultrasound of the Risk of Hepatic Cirrhosis in Cystic Fibrosis

Study Overview
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Brief Summary
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The specific aims for this study are: To determine if sonographic findings predict the risk of progression of liver disease to cirrhosis by comparing cystic fibrosis subjects with heterogeneous echogenicity pattern on ultrasound to those with normal echogenicity pattern on ultrasound To develop a database and biorepository of serum, plasma, urine and DNA to aid the investigations in ascertaining the mechanisms, consequences, genetic risk factors and biomarkers for the development of cirrhosis To determine if there are differences in health related quality of life, pulmonary or nutritional status in children with cystic fibrosis who have a heterogeneous echo pattern on ultrasound compared to those who have a normal echo pattern on ultrasound To determine if Doppler velocity measurements of hepatic and splenic vessels predict an increased risk for the development of cirrhosis. To determine if cirrhosis on ultrasound progresses to portal hypertension during the study period To determine if homogeneous liver progresses to either cirrhosis or heterogeneous liver. To determine the frequency of complications of portal hypertension during follow up in those identified with cirrhosis by year 6 of the study

Detailed Description
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For subjects in longitudinal follow up, this study will: Collect detailed clinical and demographic information about each subject at enrollment and during follow up, Obtain and store imaging data from the subject at entry and during follow up, Obtain and store serum, plasma and urine samples from the subject at entry (after matching) and during follow up, Obtain and store DNA from the subject, Obtain and store DNA from the biological parents, Obtain and store quality of life data from the subject and parents at enrollment and during follow up

Official Title
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Prediction by Ultrasound of the Risk of Hepatic Cirrhosis in Cystic Fibrosis (PUSH)

Conditions
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Cystic Fibrosis, Pancreatic Insufficiency

Intervention / Treatment
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* Procedure: Abdominal Ultrasound
* Other: Sample collection procedures


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Children aged 3 through 12 years of age at time of enrollment diagnosed with Cystic Fibrosis and pancreatic insufficiency Enrolled in the CFF registry study or Toronto CF Registry CF defined as sweat chloride of >60 mEq/L on one occasion (using the value in the CF registry) or two disease-causing mutations of CFTR with evidence of end organ involvement. Pancreatic insufficient defined as one of the following: CFTR Mutation associated with pancreatic insufficiency Fecal elastase <100 mcg/gm (at any time) 72 hour fecal fat with coefficient of fat absorption <85% (at any time) Exclusion Criteria: Known cirrhosis Presence of Burkholderia cepacia Short bowel syndrome defined as not on full enteral feeds by 3 months of age Presence of other serious disease precluding participation in this study (This would include patients with known other causes of chronic liver disease) If in the opinion of the Investigator the study is not in the best interest of the patient Inability to comply with the longitudinal follow-up described below Failure of a family to sign the informed consent document or the HIPAA medical record release form

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Group A<br>Approximately 60 subjects with a heterogeneous echo pattern of the liver on abdominal ultrasound (HTG US). | Procedure: Abdominal Ultrasound<br>* To establish eligibility and/or markers regarding echo pattern types.<br>* Other names: Doppler Ultrasound;Other: Sample collection procedures<br>* Samples of urine, serum, plasma, and blood for DNA from children and blood for DNA from parents will be requested from participating subjects<br>* Other names: Doppler Ultrasound;|
| Group B<br>Approximately 680 subjects with a normal echo pattern on abdominal ultrasound (NL US). Of these subjects, approximately 110 will be matched 1:1 with Group A participants and followed for the duration of the study. The remaining unmatched subjects will not be followed beyond their initial visit. | Procedure: Abdominal Ultrasound<br>* To establish eligibility and/or markers regarding echo pattern types.<br>* Other names: Doppler Ultrasound;Other: Sample collection procedures<br>* Samples of urine, serum, plasma, and blood for DNA from children and blood for DNA from parents will be requested from participating subjects<br>* Other names: Doppler Ultrasound;|
| Group C<br>An estimated 30 subjects with cirrhosis pattern on abdominal ultrasound. These subjects will be followed in the study. | Procedure: Abdominal Ultrasound<br>* To establish eligibility and/or markers regarding echo pattern types.<br>* Other names: Doppler Ultrasound;Other: Sample collection procedures<br>* Samples of urine, serum, plasma, and blood for DNA from children and blood for DNA from parents will be requested from participating subjects<br>* Other names: Doppler Ultrasound;|
| Group D<br>An estimated 30 subjects with diffusely homogeneous echogenic pattern at screening ultrasound will be followed in the study. | Procedure: Abdominal Ultrasound<br>* To establish eligibility and/or markers regarding echo pattern types.<br>* Other names: Doppler Ultrasound;Other: Sample collection procedures<br>* Samples of urine, serum, plasma, and blood for DNA from children and blood for DNA from parents will be requested from participating subjects<br>* Other names: Doppler Ultrasound;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Development of cirrhosis, as defined by imaging criteria | The primary objective of this prospective longitudinal study is to determine the utility of abdominal ultrasound (US) at enrollment to predict the development of cirrhosis in subjects with cystic fibrosis (CF) within a nine year period. | Nine years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effects on associated pulmonary and nutritional issues | Health related quality of life Growth (length, weight and BMI Z-score, anthropometrics) AST,ALT,GGTP FEV1, FVC Sputum Culture (Pseudomonas, Burkholderia cepacia) Use of IV antibiotics Hospitalization for treatment of pulmonary exacerbation CBC (WBC, Hbg, ANC, platelet count) Fat soluble vitamin levels (Vitamin E, 25 hydroxy vitamin D, Vitamin A) | 9years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cystic Fibrosis, Pancreatic insufficiency