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

• ClinicalTrials.gov Identifier: NCT01144507
• Recruitment Status: Active, not recruiting
• First Posted: June 15, 2010
• Last Update Posted: March 24, 2022
• Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Collaborator: Cystic Fibrosis Foundation
• Information provided by (Responsible Party): National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Study Description

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

Condition or disease	Intervention/treatment
Cystic Fibrosis; Pancreatic Insufficiency	Procedure: Abdominal Ultrasound; Other: Sample collection procedures

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

Study Design

• Study Type: Observational
• Estimated Enrollment: 800 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Prediction by Ultrasound of the Risk of Hepatic Cirrhosis in Cystic Fibrosis (PUSH)
• Actual Study Start Date: January 2009
• Estimated Primary Completion Date: June 2023
• Estimated Study Completion Date: June 2023

Groups and Cohorts

Group/Cohort	Intervention/treatment
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

Outcome Measures

Primary Outcome Measures :

1. Development of cirrhosis, as defined by imaging criteria [ Time Frame: Nine years ]
   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.

Secondary Outcome Measures :

1. Effects on associated pulmonary and nutritional issues [ Time Frame: 9years ]
   • 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.

Eligibility Criteria

• Ages Eligible for Study: 3 Years to 12 Years (Child)
• Sexes Eligible for Study: All
• 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

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

Saint 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

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

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:

PUSH is a study in the ChiLDREN Network 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• ClinicalTrials.gov Identifier: NCT01144507
• Other Study ID Numbers: CFLD PUSH; U01DK062456 ( U.S. NIH Grant/Contract )
• First Posted: June 15, 2010
• Last Update Posted: March 24, 2022
• Last Verified: March 2022

Keywords provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):

Cystic Fibrosis; Pancreatic insufficiency

Additional relevant MeSH terms:

Cystic Fibrosis; Liver Cirrhosis; Fibrosis; Liver Diseases; Exocrine Pancreatic Insufficiency; Pathologic Processes; Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Infant, Newborn, Diseases