Nitrate Effect on Exercise Capacitance (NEET)

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

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.

Study Overview

• Status: Completed
• Conditions: Fontan
• Intervention / Treatment: Drug: Isosorbide Dinitrate

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Childrens Hospital Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 9 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Isosorbide Dinitrate; 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; 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.; Other Names: Isordil

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Children's Hospital Medical Center, Cincinnati

Study record dates

Study Major Dates

• Study Start (Actual): December 12, 2019
• Primary Completion (Actual): June 30, 2020
• Study Completion (Actual): May 3, 2021

Study Registration Dates

• First Submitted: February 5, 2020
• First Submitted That Met QC Criteria: March 3, 2020
• First Posted (Actual): March 5, 2020

Study Record Updates

• Last Update Posted (Actual): September 22, 2021
• Last Update Submitted That Met QC Criteria: August 25, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Natriuretic Agents; Diuretics, Osmotic; Diuretics; Nitric Oxide Donors; Isosorbide; Isosorbide Dinitrate; Isosorbide-5-mononitrate
• Other Study ID Numbers: 2018-0020 (Other Identifier: M D Anderson Cancer Center)

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.: Yes