Nitrate Effect on Exercise Capacitance

Study Overview
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Brief Summary
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The investigators will investigate the safety and preliminary efficacy of ISDN therapy to reduce venous congestion and improve exercise tolerance in children and adults after the Fontan operation. This will be accomplished by recruiting 15 Fontan physiology patients from the Cincinnati Children's Fontan clinic and University of Kentucky Pediatric Cardiology clinic for the investigation. The investigators will non-invasively measure both central venous pressures at rest and during graded cardiopulmonary exercise testing. In addition the study team will obtain a measurement of liver stiffness before and after a 4-week regimen of ISDN therapy. Patients will be seen twice in clinic, once before and after ISDN therapy, and phone calls will be made to ensure safety, compliance, and make appropriate alterations to medications throughout the study period. Pre- and post-intervention central venous pressure and exercise tolerance will be compared.

Official Title
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Nitrate Effect on Exercise Capacitance and Hemodynamic Profile Prior to Fontan Failure

Conditions
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Fontan

Intervention / Treatment
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* Drug: Isosorbide Dinitrate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Underlying Fontan physiology On a stable medication regimen for the past 3 months Nine years of age or older Exclusion Criteria: Pregnant or nursing Prior hospitalization for heart failure in past year Presence of uncontrolled arrhythmias within the past 6 months Non-cardiac conditions which significantly limited exercise Moderate or severe ventricular dysfunction by echocardiogram or cardiac MRI Currently treated with a phosphodiesterase-5 inhibitor or organic nitrates Concurrent enrollment in other investigational drug trial End stage Liver Disease (ESLD)

Ages Eligible for Study
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Minimum Age: 9 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Isosorbide Dinitrate<br>Each enrolled participant will be on a titrated dosage of isosorbide dinitrate to determine effectiveness on both primary and secondary outcome measures. | Drug: Isosorbide Dinitrate<br>* All patients will be given a 6 week titration regimen of study medication. Patients will begin at a 5mg dosage and titrate up to 30mg three times per day if each subsequent dose is tolerated.<br>* Other names: Isordil;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Experience an Adverse Reaction to the Study Medication During the Study Enrollment Period. | Potential adverse side effects of study medication (isosorbide dinitrate) will be monitored throughout study period. Study medication will be titrated to a maximal dose of 30mg dependent on the patient tolerance. Patient tolerance is defined by frequency of known risk factors to the study medication (headaches, hypotension, and syncope). | Baseline and 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of Isosorbide Dinitrate on Liver Stiffness Levels | Determine effectiveness of study medication on hemodynamic profile by completing baseline and post-study medication liver ultrasound measuring liver stiffness levels by sheer wave speed (m/s). | Baseline and 6 weeks | 
| Effect of Isosorbide Dinitrate on Central Venous Pressure | Determine effectiveness of study medication on hemodynamic profile by completing baseline and post-study medication maximal exercise tests to measure central venous pressure via IV catheter insertion | Baseline and 6 weeks | 
| Effect of Isosorbide Dinitrate on Maximal Exercise Capacity VO2 Max | Obtain estimates of the effect the study medication has on maximal exercise test VO2 max performance in Fontan patients by study participants performing a maximal ramp exercise test on a stationary bike. | Baseline and 6 weeks | 
| Effect of Isosorbide Dinitrate on Maximal Exercise Capacity Heart Rate Response | Obtain estimates of the effect the study medication has on maximal exercise test heart rate response in Fontan patients by study participants performing a maximal ramp exercise test on a stationary bike. | Baseline and 6 weeks | 
| Effect of Isosorbide Dinitrate on Maximal Exercise Capacity Respiratory Rate Response | Obtain estimates of the effect the study medication has on maximal exercise test respiratory rate response in Fontan patients by study participants performing a maximal ramp exercise test on a stationary bike. | Baseline and 6 weeks |