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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Cystic Fibrosis Foundation Therapeutics
Information provided by (Responsible Party):
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
ClinicalTrials.gov Identifier:
NCT01144507
First received: June 14, 2010
Last updated: December 17, 2015
Last verified: December 2015
History of Changes

June 14, 2010
December 17, 2015
January 2009
November 2018   (final data collection date for primary outcome measure)
Development of cirrhosis, as defined by imaging criteria [ Time Frame: Five years ] [ Designated as safety issue: No ]
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 five year period.
Same as current
Complete list of historical versions of study NCT01144507 on ClinicalTrials.gov Archive Site
Effects on associated pulmonary and nutritional issues [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • 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)
Same as current
Not Provided
Not Provided
 
Prediction by Ultrasound of the Risk of Hepatic Cirrhosis in Cystic Fibrosis
Prediction by Ultrasound of the Risk of Hepatic Cirrhosis in Cystic Fibrosis (PUSH)

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.

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
Observational
Observational Model: Cohort
Time Perspective: Prospective
Not Provided
Retention:   Samples With DNA
Description:
During this study, blood and urine specimens will be obtained, de-identified and shipped to and stored at the NIDDK repositories for use in future CFLD ancillary studies. This "biobanking" is a critical aspect of this longitudinal study to facilitate the creation of a resource of DNA and other specimens from a meaningful number of patients with CFLD. In addition, obtaining and storing DNA or EBV-transformed leukocytes (from which DNA can be extracted) will allow future studies to investigate genetic causes and influences (modifier genes) in CFLD.
Non-Probability Sample
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.
  • Cystic Fibrosis
  • Pancreatic Insufficiency
  • Procedure: Abdominal Ultrasound
    To establish eligibility and/or markers regarding echo pattern types.
    Other Name: Doppler Ultrasound
  • Other: Sample collection procedures
    Samples of urine, serum, plasma, and blood for DNA from children and blood for DNA from parents will be requested from participating subjects
    Other Name: Doppler Ultrasound
  • Group A
    Approximately 60 subjects with a heterogeneous echo pattern of the liver on abdominal ultrasound (HTG US).
    Interventions:
    • Procedure: Abdominal Ultrasound
    • Other: Sample collection procedures
  • Group B
    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.
    Interventions:
    • Procedure: Abdominal Ultrasound
    • Other: Sample collection procedures
  • Group C
    An estimated 30 subjects with cirrhosis pattern on abdominal ultrasound. These subjects will be followed in the study.
    Interventions:
    • Procedure: Abdominal Ultrasound
    • Other: Sample collection procedures
  • Group D
    An estimated 30 subjects with diffusely homogeneous echogenic pattern at screening ultrasound will be followed in the study.
    Interventions:
    • Procedure: Abdominal Ultrasound
    • Other: Sample collection procedures
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
800
November 2018
November 2018   (final data collection date for primary outcome measure)

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
Both
3 Years to 12 Years   (Child)
No
Contact information is only displayed when the study is recruiting subjects
United States,   Canada
 
NCT01144507
CFLD PUSH
Yes
Not Provided
Not Provided
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Cystic Fibrosis Foundation Therapeutics
Study Chair: Michael Narkewicz, MD Children's Hospital Colorado
Study Director: Ed Doo, MD National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Study Director: Averell Sherker, MD National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
December 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP