Investigating fibrosis in children with single ventricle physiology

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

This study is testing how a new heart medication might help young children with single ventricle conditions by looking at the effects of fibrosis on their heart and liver health.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 145 (estimated)
• Ages: 1 Year to 6 Years
• Sex: All
• Sponsor: Children's Hospital of Philadelphia (Academic / other)
• Locations: 1 site (Philadelphia, Pennsylvania)
• Trial ID: NCT04901975 on ClinicalTrials.gov

What this trial studies

This study aims to non-invasively characterize the fibrotic consequences of single ventricle physiology in young patients undergoing Fontan operations. It examines the relationship between liver and cardiac fibrosis, lymphatic congestion, and the effects of the antifibrotic agent spironolactone. By utilizing serum biomarkers and advanced MRI techniques, the study seeks to understand the early development of these complications and their impact on patient health. Participants will include children aged 1 to 6 years with single ventricle conditions and healthy controls undergoing MRI at the Children's Hospital of Philadelphia.

Who should consider this trial

Good fit: Ideal candidates are children aged 1 to 6 years with single ventricle physiology scheduled for a Fontan operation.

Not a fit: Patients with conditions unrelated to single ventricle physiology or those outside the specified age range may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved management and prevention of fibrosis-related complications in children with single ventricle physiology.

How similar studies have performed: While there is ongoing research in this area, this specific approach combining MRI and serum biomarkers with spironolactone is relatively novel.

Eligibility criteria

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:

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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.

Where this trial is running

Philadelphia, Pennsylvania

• Children's Hospital of Philadelphia — Philadelphia, Pennsylvania, United States (Recruiting)

Study contacts

• Principal investigator: Mark Fogel, MD — Children's Hospital of Philadelphia
• Study coordinator: Mark Fogel, MD

Conditions Single-ventricle