Nitrate Effect on Exercise Capacitance

Fontan Clinical Trial

— NEET  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04297241
• Other study ID #: 2018-0020
• Status: Completed
• Phase: Phase 2
• Start date: December 12, 2019
• Est. completion date: May 3, 2021

Study information

• Verified date: July 2021
• Source: Children's Hospital Medical Center, Cincinnati
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: May 3, 2021
• Est. primary completion date: June 30, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 9 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Fontan

Intervention

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.

Locations

Country	Name	City	State
United States	Cincinnati Childrens Hospital Medical Center	Cincinnati	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Children's Hospital Medical Center, Cincinnati

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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