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
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: September 15, 2014
Last verified: September 2014
  Purpose

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.

Condition Intervention
Cystic Fibrosis
Pancreatic Insufficiency
Procedure: Abdominal Ultrasound
Other: Sample collection procedures

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Prediction by Ultrasound of the Risk of Hepatic Cirrhosis in Cystic Fibrosis (PUSH)

Resource links provided by NLM:


Further study details as provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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)


Biospecimen Retention:   Samples With DNA

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.


Estimated Enrollment: 800
Study Start Date: January 2009
Estimated Study Completion Date: November 2018
Estimated Primary Completion Date: November 2018 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Group A
Approximately 60 subjects with a heterogeneous echo pattern of the liver on abdominal ultrasound (HTG US).
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 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.
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 C
An estimated 30 subjects with cirrhosis pattern on abdominal ultrasound. These subjects will be followed in the study.
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 D
An estimated 30 subjects with diffusely homogeneous echogenic pattern at screening ultrasound will be followed in the study.
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

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

Ages Eligible for Study:   3 Years to 12 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01144507

Locations
United States, Colorado
Children's Hospital of Colorado
Aurora, Colorado, United States, 80045
United States, Georgia
Emory University School of Medicine
Atlanta, Georgia, United States, 30322
United States, Illinois
Ann & Robert H. Lurie Children's Hospital of
Chicago, Illinois, United States, 60611
United States, Indiana
Riley Hospital for Children
Indianapolis, Indiana, United States, 46202
United States, Maryland
Johns Hopkins School of Medicine
Baltimore, Maryland, United States, 21287
United States, Minnesota
University of Minneapolis Medical Center
Minneapolis, Minnesota, United States, 55455
United States, Missouri
Washington University School of Medicine
St. Louis, Missouri, United States, 63110
United States, Ohio
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229
United States, Texas
Texas Children's Hospital
Houston, Texas, United States, 77030
United States, Washington
Seattle Children's Hospital
Seattle, Washington, United States, 98105
Canada, Ontario
Hospital for Sick Children
Toronto, Ontario, Canada, M5G 1X8
Sponsors and Collaborators
Cystic Fibrosis Foundation
Investigators
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)
  More Information

Additional Information:
No publications provided

Responsible Party: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
ClinicalTrials.gov Identifier: NCT01144507     History of Changes
Other Study ID Numbers: CFLD PUSH
Study First Received: June 14, 2010
Last Updated: September 15, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):
Cystic Fibrosis
Pancreatic insufficiency

Additional relevant MeSH terms:
Fibrosis
Cystic Fibrosis
Exocrine Pancreatic Insufficiency
Liver Cirrhosis
Pathologic Processes
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Liver Diseases

ClinicalTrials.gov processed this record on September 22, 2014