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

NCT ID: NCT01144507

Last Updated: 2025-04-11

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

774 participants

Study Classification

OBSERVATIONAL

Study Start Date

2010-01-12

Study Completion Date

2023-06-14

Brief Summary

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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

Detailed Description

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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

Conditions

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Cystic Fibrosis Pancreatic Insufficiency

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Group A

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

Abdominal Ultrasound

Intervention Type PROCEDURE

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

Sample collection procedures

Intervention Type OTHER

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

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.

Abdominal Ultrasound

Intervention Type PROCEDURE

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

Sample collection procedures

Intervention Type OTHER

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

Group C

An estimated 30 subjects with cirrhosis pattern on abdominal ultrasound. These subjects will be followed in the study.

Abdominal Ultrasound

Intervention Type PROCEDURE

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

Sample collection procedures

Intervention Type OTHER

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

Group D

An estimated 30 subjects with diffusely homogeneous echogenic pattern at screening ultrasound will be followed in the study.

Abdominal Ultrasound

Intervention Type PROCEDURE

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

Sample collection procedures

Intervention Type OTHER

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

Interventions

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Abdominal Ultrasound

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

Intervention Type PROCEDURE

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

Intervention Type OTHER

Other Intervention Names

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Doppler Ultrasound Doppler Ultrasound

Eligibility Criteria

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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
Minimum Eligible Age

3 Years

Maximum Eligible Age

12 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Cystic Fibrosis Foundation

OTHER

Sponsor Role collaborator

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

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Michael Narkewicz, MD

Role: STUDY_CHAIR

Children's Hospital Colorado

Ed Doo, MD

Role: STUDY_DIRECTOR

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

Averell Sherker, MD

Role: STUDY_DIRECTOR

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

Locations

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Children's Hospital of Colorado

Aurora, Colorado, United States

Site Status

Emory University School of Medicine

Atlanta, Georgia, United States

Site Status

Ann & Robert H. Lurie Children's Hospital of

Chicago, Illinois, United States

Site Status

Riley Hospital for Children

Indianapolis, Indiana, United States

Site Status

Johns Hopkins School of Medicine

Baltimore, Maryland, United States

Site Status

University of Minneapolis Medical Center

Minneapolis, Minnesota, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Site Status

Texas Children's Hospital

Houston, Texas, United States

Site Status

Seattle Children's Hospital

Seattle, Washington, United States

Site Status

Hospital for Sick Children

Toronto, Ontario, Canada

Site Status

Countries

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United States Canada

References

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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.

Reference Type BACKGROUND
PMID: 32061406 (View on PubMed)

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.

Reference Type DERIVED
PMID: 37032248 (View on PubMed)

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.

Reference Type DERIVED
PMID: 26254836 (View on PubMed)

Related Links

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http://www.childrennetwork.org/

PUSH is a study in the ChiLDREN Network

Other Identifiers

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U01DK062456

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CFLD PUSH

Identifier Type: -

Identifier Source: org_study_id

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