Prediction by Ultrasound of the Risk of Hepatic Cirrhosis in Cystic Fibrosis

NCT01144507 | Completed DMC

• 2 other identifiers: CFLD PUSHU01DK062456
• Study Type: observational
• Target: 774
• Locations: 2 countries
• Sites: 11

Brief Summary

The specific aims for this study are:

1. 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. 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. 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. 4.To determine if Doppler velocity measurements of hepatic and splenic vessels predict an increased risk for the development of cirrhosis.
5. 5.To determine if cirrhosis on ultrasound progresses to portal hypertension during the study period
6. 6.To determine if homogeneous liver progresses to either cirrhosis or heterogeneous liver.
7. 7.To determine the frequency of complications of portal hypertension during follow up in those identified with cirrhosis by year 6 of the study

Conditions

Cystic Fibrosis; Pancreatic Insufficiency

Keywords

Cystic Fibrosis; Pancreatic insufficiency

Outcome Measures

Primary Outcomes (1)

• Development of cirrhosis, as defined by imaging criteria

  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.

  Nine years

Secondary Outcomes (1)

• Effects on associated pulmonary and nutritional issues

  9years

Study Arms (4)

Group A

Approximately 60 subjects with a heterogeneous echo pattern of the liver on abdominal ultrasound (HTG US).

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.

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.

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.

Procedure: Abdominal Ultrasound; Other: Sample collection procedures

Interventions

Abdominal Ultrasound PROCEDURE

To establish eligibility and/or markers regarding echo pattern types.

Also known as: Doppler Ultrasound

Group A; Group B; Group C; Group D

Sample collection procedures OTHER

Samples of urine, serum, plasma, and blood for DNA from children and blood for DNA from parents will be requested from participating subjects

Also known as: Doppler Ultrasound

Group A; Group B; Group C; Group D

Eligibility Criteria

• Age: 3 Years - 12 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)
• 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.

You may qualify if:

• 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)
• hour fecal fat with coefficient of fat absorption \<85% (at any time)

You may not qualify if:

• 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

Sponsors & Collaborators

• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): lead
• Cystic Fibrosis Foundation: collaborator

Study Sites (11)

Children's Hospital of Colorado

Aurora, Colorado, 80045, United States

Location

Emory University School of Medicine

Atlanta, Georgia, 30322, United States

Location

Ann & Robert H. Lurie Children's Hospital of

Chicago, Illinois, 60611, United States

Location

Riley Hospital for Children

Indianapolis, Indiana, 46202, United States

Location

Johns Hopkins School of Medicine

Baltimore, Maryland, 21287, United States

Location

University of Minneapolis Medical Center

Minneapolis, Minnesota, 55455, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

Location

Related Publications (3)

• 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.

  PMID: 32061406 BACKGROUND

• Siegel MJ, Leung DH, Molleston JP, Ye W, Paranjape SM, Freeman AJ, Palermo JJ, Stoll J, Masand P, Karmazyn B, Harned R, Ling SC, Navarro OM, Karnsakul W, Alazraki A, Schwarzenberg SJ, Towbin AJ, Alonso EM, Nicholas JL, Green N, Otto RK, Magee JC, Narkewicz MR. Heterogeneous liver on research ultrasound identifies children with cystic fibrosis at high risk of advanced liver disease. J Cyst Fibros. 2023 Jul;22(4):745-755. doi: 10.1016/j.jcf.2023.03.019. Epub 2023 Apr 7.

  PMID: 37032248 DERIVED

• 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.

  PMID: 26254836 DERIVED

Related Links

• PUSH is a study in the ChiLDREN Network

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.

MeSH Terms

Conditions

Cystic Fibrosis; Exocrine Pancreatic Insufficiency

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Study Officials

• Michael Narkewicz, MD

  Children's Hospital Colorado

  STUDY CHAIR

• 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)

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 14, 2010
• First Posted: June 15, 2010
• Study Start: January 12, 2010
• Primary Completion: February 26, 2021
• Study Completion: June 14, 2023
• Last Updated: April 11, 2025

Record last verified: 2025-04

Locations

US (10); CA (1)