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

Tracking Information
First Submitted Date	June 14, 2010
First Posted Date	June 15, 2010
Last Update Posted Date	March 30, 2018
Study Start Date	January 2009
Estimated Primary Completion Date	November 2021 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures; (submitted: March 28, 2018)	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.
Original Primary Outcome Measures; (submitted: June 14, 2010)	Development of cirrhosis, as defined by imaging criteria [ Time Frame: Five 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 five year period.
Change History	Complete list of historical versions of study NCT01144507 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures; (submitted: March 28, 2018)	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)
Original Secondary Outcome Measures; (submitted: June 14, 2010)	Effects on associated pulmonary and nutritional issues [ Time Frame: 5 years ]; 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)
Current Other Outcome Measures	Not Provided
Original Other Outcome Measures	Not Provided
Descriptive Information
Brief Title	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)
Brief Summary	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	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
Study Type	Observational
Study Design	Observational Model: Cohort; Time Perspective: Prospective
Target Follow-Up Duration	Not Provided
Biospecimen	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.
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.
Condition	Cystic Fibrosis; Pancreatic Insufficiency
Intervention	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
Study Groups/Cohorts	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
Publications *	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.
Recruitment Information
Recruitment Status	Active, not recruiting
Estimated Enrollment; (submitted: April 23, 2012)	800
Original Estimated Enrollment; (submitted: June 14, 2010)	580
Estimated Study Completion Date	November 2021
Estimated Primary Completion Date	November 2021 (Final data collection date for primary outcome measure)
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
Sex/Gender	Sexes Eligible for Study: All
Ages	3 Years to 12 Years (Child)
Accepts Healthy Volunteers	No
Contacts	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries	Canada, United States
Removed Location Countries
Administrative Information
NCT Number	NCT01144507
Other Study ID Numbers	CFLD PUSH; U01DK062456 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee	Yes
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Study Sponsor	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Collaborators	Cystic Fibrosis Foundation Therapeutics
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)
PRS Account	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Verification Date	March 2018