Clinical trial NCT01144507: Prediction by Ultrasound of the Risk of Hepatic Cirrhosis in Cystic Fibrosis
Official title: Prediction by Ultrasound of the Risk of Hepatic Cirrhosis in Cystic Fibrosis (PUSH)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Cystic Fibrosis
Pancreatic Insufficiency
Keywords: Cystic Fibrosis
Pancreatic insufficiency
Lead sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Sponsor class: NIH
Collaborators: name: Cystic Fibrosis Foundation
First posted: 2010-06-15
Enrollment: 774
Sex: ALL
Minimum age (years): 3
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study population will consist of males and females 3 through 12 years of age with Cystic Fibrosis and pancreatic insufficiency who are enrolled in the CFF or Toronto CF registry studies. All racial and ethnic groups will be included.

Brief summary: The specific aims for this study are:

1. 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
2. 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
3. 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
4. To determine if Doppler velocity measurements of hepatic and splenic vessels predict an increased risk for the development of cirrhosis.
5. To determine if cirrhosis on ultrasound progresses to portal hypertension during the study period
6. To determine if homogeneous liver progresses to either cirrhosis or heterogeneous liver.
7. 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: For subjects in longitudinal follow up, this study will:

1. Collect detailed clinical and demographic information about each subject at enrollment and during follow up,
2. Obtain and store imaging data from the subject at entry and during follow up,
3. Obtain and store serum, plasma and urine samples from the subject at entry (after matching) and during follow up,
4. Obtain and store DNA from the subject,
5. Obtain and store DNA from the biological parents,
6. Obtain and store quality of life data from the subject and parents at enrollment and during follow up

Eligibility criteria: 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

Primary outcomes:
measure: Development of cirrhosis, as defined by imaging criteria
timeFrame: Nine years
Secondary outcomes:
measure: Effects on associated pulmonary and nutritional issues
timeFrame: 9years
Other outcomes:
Locations:
city: Aurora
country: United States
facility: Children's Hospital of Colorado
state: Colorado
city: Atlanta
country: United States
facility: Emory University School of Medicine
state: Georgia
city: Chicago
country: United States
facility: Ann & Robert H. Lurie Children's Hospital of
state: Illinois
city: Indianapolis
country: United States
facility: Riley Hospital for Children
state: Indiana
city: Baltimore
country: United States
facility: Johns Hopkins School of Medicine
state: Maryland
city: Minneapolis
country: United States
facility: University of Minneapolis Medical Center
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Houston
country: United States
facility: Texas Children's Hospital
state: Texas
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
city: Toronto
country: Canada
facility: Hospital for Sick Children
state: Ontario
Study officials:
affiliation: Children's Hospital Colorado
name: Michael Narkewicz, MD
role: STUDY_CHAIR
affiliation: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
name: Ed Doo, MD
role: STUDY_DIRECTOR
affiliation: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
name: Averell Sherker, MD
role: STUDY_DIRECTOR
References:
citation: Siegel MJ, Freeman AJ, Ye W, Palermo JJ, Molleston JP, Paranjape SM, Stoll J, Leung DH, Masand P, Karmazyn B, Harned R, Ling SC, Navarro OM, Karnsakul W, Alazraki A, Schwarzenberg SJ, Seidel FG, Towbin A, Alonso EM, Nicholas JL, Murray KF, Otto RK, Sherker AH, Magee JC, Narkewicz MR; CFLD Network. Heterogeneous Liver on Research Ultrasound Identifies Children with Cystic Fibrosis at High Risk of Advanced Liver Disease: Interim Results of a Prospective Observational Case-Controlled Study. J Pediatr. 2020 Apr;219:62-69.e4. doi: 10.1016/j.jpeds.2019.12.033. Epub 2020 Feb 12.
citation: Leung DH, Ye W, Molleston JP, Weymann A, Ling S, Paranjape SM, Romero R, Schwarzenberg SJ, Palermo J, Alonso EM, Murray KF, Marshall BC, Sherker AH, Siegel MJ, Krishnamurthy R, Harned R, Karmazyn B, Magee JC, Narkewicz MR; Cystic Fibrosis Liver Disease Network (CFLD NET). Baseline Ultrasound and Clinical Correlates in Children with Cystic Fibrosis. J Pediatr. 2015 Oct;167(4):862-868.e2. doi: 10.1016/j.jpeds.2015.06.062. Epub 2015 Aug 5.