Cystic FibrosisPUSHNCT01144507
Prediction by Ultrasound of the Risk of Hepatic Cirrhosis in Cystic Fibrosis
An observational study of Cystic Fibrosis and Pancreatic Insufficiency, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 11 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 3 to 12 years
- Conditions the study is for
- Cystic Fibrosis, Pancreatic Insufficiency
- What is being tested?
- Abdominal Ultrasound and Sample collection procedures
- Type of treatment
- Surgery or procedure
- How many people
- 774 participants
- Where
- 11 sitesin 2 countries
- Study dates
- 12 Jan 2010to 14 Jun 2023
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 3 to 12 years
- All sexes
- No healthy volunteers
- Child
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.
Who may be able to join
- 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)
Who cannot join
- 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
Trial locations and contacts
11 sites in 2 countries.
11 sites in 2 countries
United States10 sites
Emory University School of Medicine
Atlanta, Georgia, 30322
Children's Hospital of Colorado
Aurora, Colorado, 80045
Johns Hopkins School of Medicine
Baltimore, Maryland, 21287
Ann & Robert H. Lurie Children's Hospital of
Chicago, Illinois, 60611
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Texas Children's Hospital
Houston, Texas, 77030
Riley Hospital for Children
Indianapolis, Indiana, 46202
University of Minneapolis Medical Center
Minneapolis, Minnesota, 55455
Seattle Children's Hospital
Seattle, Washington, 98105
Washington University School of Medicine
St Louis, Missouri, 63110
About this study
Official title: Prediction by Ultrasound of the Risk of Hepatic Cirrhosis in Cystic Fibrosis (PUSH)
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
Read the 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
- Conditions
- Cystic Fibrosis, Pancreatic Insufficiency
- Being tested
- Abdominal Ultrasound, Sample collection procedures
- Keywords
- Cystic Fibrosis, Pancreatic insufficiency
- Medical subject headings
- Cystic Fibrosis, Exocrine Pancreatic Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Abdominal UltrasoundProcedure or surgery
Also called Doppler Ultrasound
To establish eligibility and/or markers regarding echo pattern types.
Sample collection proceduresOther
Also called Doppler Ultrasound
Samples of urine, serum, plasma, and blood for DNA from children and blood for DNA from parents will be requested from participating subjects
| Study group | Role | What they receive |
|---|---|---|
| Group A | Approximately 60 subjects with a heterogeneous echo pattern of the liver on abdominal ultrasound (HTG US). Receives: 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. Receives: 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. Receives: 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. Receives: Procedure: Abdominal Ultrasound; Other: Sample collection procedures |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Nine years
Secondary outcomes (1)
Effects on associated pulmonary and nutritional issues
- 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)
Measured: 9years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jun 2010 (estimated)
- Study start12 Jan 2010
- Primary completion26 Feb 2021
- Study completion14 Jun 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Cystic FibrosisStudies of the same condition, open and under way.
- More trials run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 774 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Collaborators
- Cystic Fibrosis Foundation
- Responsible party
- Sponsor
- Investigators
- Michael Narkewicz, MD, Study chair, Children's Hospital ColoradoEd Doo, MD, Study director, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)Averell Sherker, MD, Study director, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01144507
- Sponsor's protocol ID
- CFLD PUSH
- Other IDs
- U01DK062456
- Acronym
- PUSH
- Status last verified
- Apr 2025
- First submitted
- 14 Jun 2010
- Last updated
- 11 Apr 2025
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 32061406Siegel 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.
PubMed 37032248Leung 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.
PubMed 26254836
Study at a glance
From the registry record, last updated by the sponsor on 11 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prediction by Ultrasound of the Risk of Hepatic Cirrhosis in Cystic Fibrosis (PUSH)
- ClinicalTrials.gov ID
- NCT01144507
- Acronym / sponsor ID
- PUSH / CFLD PUSH
- Conditions
- Cystic Fibrosis, Pancreatic Insufficiency
- Keywords
- Cystic Fibrosis, Pancreatic insufficiency
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 774 participants (actual)
- Lead sponsor
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)US National Institutes of Health
- Collaborators
- Cystic Fibrosis Foundation
- Study start
- 12 Jan 2010 (actual)
- Primary completion
- 26 Feb 2021 (actual)
- Study completion
- 14 Jun 2023 (actual)
- First posted
- 15 Jun 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Group A | – | Procedure: Abdominal Ultrasound, Other: Sample collection proceduresApproximately 60 subjects with a heterogeneous echo pattern of the liver on abdominal ultrasound (HTG US). |
| Group B | – | Procedure: Abdominal Ultrasound, Other: Sample collection proceduresApproximately 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. |
| Group C | – | Procedure: Abdominal Ultrasound, Other: Sample collection proceduresAn estimated 30 subjects with cirrhosis pattern on abdominal ultrasound. These subjects will be followed in the study. |
| Group D | – | Procedure: Abdominal Ultrasound, Other: Sample collection proceduresAn estimated 30 subjects with diffusely homogeneous echogenic pattern at screening ultrasound will be followed in the study. |
Who may qualify
- Ages
- 3 to 12 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
- 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.
Key inclusion criteria (7 listed)
- 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:
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Abdominal UltrasoundAlso: Doppler UltrasoundTo establish eligibility and/or markers regarding echo pattern types. | Procedure or surgery | Group A, Group B, Group C, Group D |
| Sample collection proceduresAlso: Doppler UltrasoundSamples of urine, serum, plasma, and blood for DNA from children and blood for DNA from parents will be requested from participating subjects | Other | Group A, Group B, Group C, Group D |
Primary outcome
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.
1 secondary outcome
Effects on associated pulmonary and nutritional issues
Time frame: 9years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Apr 2025.
- Background: PubMed 32061406Siegel 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.
- Derived from this study: PubMed 37032248Siegel 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.
- Derived from this study: PubMed 26254836Leung 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.
- PUSH is a study in the ChiLDREN NetworkLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael Narkewicz, MD study chair
Children's Hospital Colorado
Ed Doo, MD study director
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Averell Sherker, MD study director
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
11 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Cystic Fibrosis and Pancreatic Insufficiency, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 11 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Development of cirrhosis, as defined by imaging criteria (time frame: Nine years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01144507, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Apr 2025.