Fibrosis and the Fontan

June 30, 2026 updated by: Children's Hospital of Philadelphia

Acute Imposition of Fontan Physiology in The Single Ventricle Patient: Effects on Fibrosis, Function and Drug Intervention

The purpose of this study is to non-invasively characterize the fibrotic consequences of single ventricle physiology, its possible solution and effect on lymphatics. This project investigates the response to acute imposition of Fontan hemodynamics by examining the interrelationship between liver and cardiac fibrosis/dysfunction and lymphatic congestion along with a pilot trial of the antifibrotic agent, spironolactone, to prevent these consequences and to determine if MRI can discern these differences. The combination of serum biomarkers and MRI form a powerful non-invasive tool in putting together this complicated web of dysfunction.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Fontan patients, unfortunately, suffer multiple complications such as liver fibrosis, cardiac fibrosis and lymphatic congestion. While investigations describing the clinical state are taking place in older children and young adults, the onset of these complications remains unclear. The knowledge gap this proposal seeks to fill is understanding how early liver and cardiac fibrosis develops as well as lymphatic abnormalities by assessing these before as well as early after imposition of the Fontan circulation.

Single ventricle case subjects will be between aged 1 and less than or equal to 6 years of age of either gender, whether single left or right ventricle, who are scheduled to undergo a Fontan operation at the Children's Hospital of Philadelphia (CHOP) and control subjects will be aged between 1 and less than or equal to 6 years of age with normal ventricular function and normal livers who present to CHOP for a clinically indicated MRI.

Review of medical records, demographic/social history, physical examination (performed for clinical purposes), administer study drug (spironolactone), blood tests (serum biomarkers), MRI/CMR (including a non-FDA approved MRI sequence), liver assessment, administration of contrast and general anesthesia for case subjects (in some instances, an extension of clinically indicated anesthesia for control and some case subjects approximately 15-20 minutes) as applicable.

The difference between enrollment and 1 year after Fontan surgery for a) liver fibrosis measured by Magnetic Resonance Elastography (MRE) and T1 mapping, b) cardiac fibrosis measured by T1 mapping using global extracellular volume (ECV) and c) percentage of myocardial mass which demonstrates delayed enhancement (DE). This is for both non-drug and spironolactone administered groups

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
98

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.
  • Name: Mark Fogel, MD
  • Phone Number: 215-590-4040
  • Email: fogel@chop.edu

Study Contact Backup

  • Name: Cassandra L Giner, MS
  • Phone Number: 915-503-3642
  • Email: ginerc@chop.edu

Study Locations

  • United States
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19130
        • Children's Hospital of Philadelphia

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

1 year to 6 years (Child)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Single Ventricle (SV) Patients

Cohort 1 (Observational Group - no study medication):

  • Subjects between 1 and ≤ 6 years of age of either gender.
  • Either single left or single right ventricle.
  • Subjects who are scheduled to undergo a Fontan operation at CHOP.
  • Parents signing informed consent.

Cohort 1A (formerly part of study drug group who wish continued participation in the observational group):

  • Subjects who were enrolled in this study in Cohort 2 and are either non-compliant with the medication, no longer want to take the medication, or have an AE that requires them to stop the medication, and patient's family would like to continue participation
  • Patients were on study medication for 6 weeks or less.
  • The principal investigator deems it appropriate for the patient to switch to the observational arm.
  • Patients signing the observational informed consent form.

Cohort 1B (observational group - in other studies with intervention):

  • Subjects between 1 and ≤6 years of age of either gender.
  • Either single left or single right ventricle.
  • Subjects who are planned to undergo a Fontan operation at CHOP.
  • Patients in other interventional studies approved by principal investigator.
  • Patients signing the observational informed consent form.

Cohort 2 (study drug Group - spironolactone):

  • Subjects between 1 and ≤ 6 years of age of either gender.
  • Either single left or single right ventricle.
  • Subjects who are scheduled to undergo a Fontan operation at CHOP.
  • Parents signing informed consent.

Controls

  • Subjects between 1 and ≤ 6 years of age of either gender
  • Subjects with normal ventricular function and normal livers who present to CMR for clinical indications and require anesthesia.
  • Receiving contrast for clinical purposes. No control patient will receive contrast for research purposes.
  • Parents signing informed consent.

Exclusion Criteria:

-

Cohort 1 (Observational Group - no study medication):

  • Subjects with any condition judged by the patient's physician that would cause this trial to be detrimental to the patient.
  • Any contradiction to a sedated CMR (i.e. presence of a pacemaker).
  • Patient currently taking spironolactone or eplerenone
  • Subjects in any study that would preclude participation in the study by altering results

Cohort 1A (formerly part of study drug group who wish continued participation in the observational group):

  • Subjects with any condition judged by the patient's physician that would cause this trial to be detrimental to the patient.
  • Any contradiction to a sedated CMR (i.e. presence of a pacemaker).
  • Subjects in any study that would preclude participation in the current study.

Cohort 1B (observational group - in other studies with intervention):

  • Subjects with any condition judged by the patient's physician that would cause this trial to be detrimental to the patient.
  • Any contradiction to a sedated CMR (i.e. presence of a pacemaker).
  • Patient currently taking spironolactone or eplerenone
  • Subjects in any study that would preclude participation in the current study or studies not approved by principal investigator.

Cohort 2 (Study Drug Group - Spironolactone):

  • Subjects with any condition judged by the patient's physician that would cause this trial to be detrimental to the patient.
  • Any contradiction to a sedated CMR (i.e. presence of a pacemaker).
  • Patient currently taking spironolactone or eplerenone
  • Subjects with hyperkalemia or Addison disease;
  • Subjects on enalapril or other angiotensin receptor blockers
  • Subjects with a history of hypersensitivity to spironolactone suspension or any component of the formulation
  • Subjects with a clinically documented diagnosis of severe renal insufficiency (implying estimated glomerular filtration rate (eGFR) <30 mL/minute/1.73 m2).
  • Subjects in any study that would preclude participation in the study by altering results

Controls

  • Any condition judged by the patient's physician that would cause this trial to be detrimental to the patient.
  • Any contradiction to a sedated CMR (i.e. presence of a pacemaker).
  • Patient currently taking spironolactone, eplerenone or an angiotensin converting the enzyme inhibitor/angiotensin receptor blocker.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Spironolactone

Children will undergo characterization and measurement of liver and cardiac fibrosis with MRI and cardiac magnetic resonance (CMR) as well as serum biomarkers immediately prior to the Fontan operation.

All SV children will undergo characterization and measurement of liver and cardiac fibrosis with MRI and cardiac magnetic resonance (CMR) as well as serum biomarkers ~1 year after the Fontan operation.

Spironolactone is a mild diuretic. Drug dosage will be those used clinically and per the CHOP formulary: 3 mg/kg/day in divided doses every 6-24 hours; the drug will be weight adjusted every ~0.5 kg with a maximum dosage of 200 mg/24 hours. Maximum single dose is 100 mg.

Spironolactone administration will begin after the Fontan procedure in the hospital prior to discharge or at the first outpatient visit ~ 2 weeks after discharge.
Drug: Spironolactone
Spironolactone is a mild diuretic. Drug dosage will be those used clinically and per the CHOP formulary: 3 mg/kg/day in divided doses every 6-24 hours; the drug will be weight adjusted every ~0.5 kg with a maximum dosage of 200 mg/24 hours. Maximum single dose is 100 mg. Spironolactone, the aldosterone antagonist to be utilized in Specific Aim 2 of this study, is FDA approved, has been on the market for many years and is routinely administered to all types of children with congenital heart disease including SV patients. The choice of which patient this should be administered to is up to the clinician and their patients and therefore, not all SV patients are on this medication.
No Intervention: Observational

Children will undergo characterization and measurement of liver and cardiac fibrosis with MRI and cardiac magnetic resonance (CMR) as well as serum biomarkers immediately prior to the Fontan operation.

All SV children, whether they received spironolactone or not, will undergo characterization and measurement of liver and cardiac fibrosis with MRI and cardiac magnetic resonance (CMR) as well as serum biomarkers ~1 year after the Fontan operation. Demographics and medical history will be collected again along with adverse events. Children will also undergo CMR for evaluation of hemodynamics, ventricular function (including strain), computational modeling and lymphatic abnormalities. A few of these patients will be undergoing CMR for clinical reasons and study CMR related and study MRI related imaging and blood draws will be performed in coordination with their clinical care (ie these sequences will be added on to their clinical sequences).
No Intervention: Control

The purpose of this study is to non-invasively characterize the fibrotic consequences of SV physiology, its possible solution and effect on lymphatics. This project investigates the response to acute imposition of Fontan hemodynamics by examining the interrelationship between liver and cardiac fibrosis/dysfunction and lymphatic congestion (figure 1) along with a pilot trial of the antifibrotic agent, spironolactone, to prevent these consequences and to determine if MRI can discern these differences. The combination of serum biomarkers and MRI form a powerful non-invasive tool in putting together this complicated web of dysfunction.

Control subjects who are non-SV patients but who have normal heart function who are undergoing CMR for evaluation (eg patients undergoing CMR for vascular ring evaluation, family history of congenital heart disease but found to be normal, etc) will have study related MRI and CMR sequences performed.
No Intervention: Observational - 1A

Subjects who were enrolled in this study in Spironolactone arm and patient's family would like to continue participation.

All SV children, whether they received spironolactone or not, will undergo characterization and measurement of liver and cardiac fibrosis with MRI and cardiac magnetic resonance (CMR) as well as serum biomarkers ~1 year after the Fontan operation. Demographics and medical history will be collected again along with adverse events. Children will also undergo CMR for evaluation of hemodynamics, ventricular function (including strain), computational modeling and lymphatic abnormalities. A few of these patients will be undergoing CMR for clinical reasons and study CMR related and study MRI related imaging and blood draws will be performed in coordination with their clinical care (ie these sequences will be added on to their clinical sequences).
No Intervention: Observational - 1B

Subjects who were enrolled in other studies with intervention.

All SV children, whether they received spironolactone or not, will undergo characterization and measurement of liver and cardiac fibrosis with MRI and cardiac magnetic resonance (CMR) as well as serum biomarkers ~1 year after the Fontan operation. Demographics and medical history will be collected again along with adverse events. Children will also undergo CMR for evaluation of hemodynamics, ventricular function (including strain), computational modeling and lymphatic abnormalities. A few of these patients will be undergoing CMR for clinical reasons and study CMR related and study MRI related imaging and blood draws will be performed in coordination with their clinical care (ie these sequences will be added on to their clinical sequences).

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Liver elastography by MRE prior to and after Fontan
Time Frame: up to 1 year
Measured by MRE for viscoelastic properties of the liver, primarily stiffness
up to 1 year
Liver elastography by T1rho prior to and after Fontan
Time Frame: up to 1 year
Measured by T1rho mapping for further viscoelastic properties of the liver, primarily hepatic fibrosis
up to 1 year
Heart tissue characterization by T1 mapping prior to and after Fontan
Time Frame: up to 1 year
Measured by T1 mapping using global extracellular volume (ECV)
up to 1 year
Heart tissue characterization prior to and after Fontan
Time Frame: up to 1 year
Percentage of myocardial mass which demonstrates delayed enhancement
up to 1 year

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Serum biomarkers of fibrosis
Time Frame: up to 1 year
Serum biomarkers of liver will be assessed to include eg Galectin-3, PIIIP and TGF-beta
up to 1 year
Lymphatic dysfunction by MRE prior to and after Fontan
Time Frame: up to 1 year
Lymphatic dysfunction will be measured by MRE to find if lesions are present
up to 1 year
Lymphatic dysfunction T1rho prior to and after Fontan
Time Frame: up to 1 year
Lymphatic dysfunction will be measured by T1rho to find if lesions are present
up to 1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Children's Hospital of Philadelphia

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Heart, Lung, and Blood Institute (NHLBI)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Mark Fogel, MD, Children's Hospital of Philadelphia

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 11, 2021

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 30, 2026

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 30, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 14, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 20, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 26, 2021

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 1, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 30, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 20-017716
  • 1R01HL149139-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings