Fibrosis and the Fontan

• Status: Recruiting
• Trial end date: 2024-06-30
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Children's Hospital of Philadelphia
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI)
• Treatments: Spironolactone

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 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

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).

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.