FontanPhase 2NEETNCT04297241
Nitrate Effect on Exercise Capacitance
A Phase 2 study testing Isosorbide Dinitrate in people with Fontan, run by Children's Hospital Medical Center, Cincinnati at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 9 years and older
- Conditions the study is for
- Fontan
- What is being tested?
- Isosorbide Dinitrate
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- 12 Dec 2019to 3 May 2021
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 9 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Underlying Fontan physiology
- On a stable medication regimen for the past 3 months
- Nine years of age or older
Who cannot join
- 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)
Trial locations and contacts
1 site in 1 country.
United States1 site
Cincinnati Childrens Hospital Medical Center
Cincinnati, Ohio, 45229
About this study
Official title: 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.
- Conditions
- Fontan
- Being tested
- Isosorbide Dinitrate
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Isosorbide DinitrateDrug
Also called Isordil
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.
| Study group | Role | What they receive |
|---|---|---|
| Isosorbide Dinitrate | Experimental | Each enrolled participant will be on a titrated dosage of isosorbide dinitrate to determine effectiveness on both primary and secondary outcome measures. Receives: Drug: Isosorbide Dinitrate |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: Baseline and 6 weeks
Secondary outcomes (5)
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).
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Baseline and 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Mar 2020
- Study start12 Dec 2019
- Primary completion30 Jun 2020
- Study completion3 May 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for FontanStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Hospital Medical Center, Cincinnati
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04297241
- Sponsor's protocol ID
- 2018-0020
- Acronym
- NEET
- Status last verified
- Jul 2021
- First submitted
- 5 Feb 2020
- Last updated
- 22 Sep 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Bigelow AM, Riggs KW, Morales DLS, Opotowsky AR, Lubert AM, Dillman JR, Veldtman GR, Heydarian HC, Trout AT, Cooper DS, Goldstein SL, Chin C, Palermo JJ, Ollberding NJ, Mays WA, Alsaied T. Isosorbide DiNitrate Effect on Hemodynamic Profile, Liver Stiffness, and Exercise Tolerance in Fontan Circulation (The NEET Clinical Trial). Pediatr Cardiol. 2024 Oct;45(7):1389-1397. doi: 10.1007/s00246-023-03156-3. Epub 2023 Apr 21.
PubMed 37084132
Study at a glance
From the registry record, last updated by the sponsor on 22 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Nitrate Effect on Exercise Capacitance and Hemodynamic Profile Prior to Fontan Failure
- ClinicalTrials.gov ID
- NCT04297241
- Acronym / sponsor ID
- NEET / 2018-0020
- Conditions
- Fontan
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Children's Hospital Medical Center, CincinnatiUniversity, hospital or other
- Study start
- 12 Dec 2019 (actual)
- Primary completion
- 30 Jun 2020 (actual)
- Study completion
- 3 May 2021 (actual)
- First posted
- 5 Mar 2020 (actual)
- Results
- Posted 25 Aug 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Isosorbide Dinitrate | Experimental | Drug: Isosorbide DinitrateEach enrolled participant will be on a titrated dosage of isosorbide dinitrate to determine effectiveness on both primary and secondary outcome measures. |
Who may qualify
- Ages
- 9 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- Underlying Fontan physiology
- On a stable medication regimen for the past 3 months
- Nine years of age or older
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Isosorbide DinitrateAlso: IsordilAll 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. | Drug | Isosorbide Dinitrate |
Primary outcome
Number of Participants Who Experience an Adverse Reaction to the Study Medication During the Study Enrollment Period.
Time frame: Baseline and 6 weeks
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).
5 secondary outcomes
Effect of Isosorbide Dinitrate on Liver Stiffness Levels
Time frame: Baseline and 6 weeks
Effect of Isosorbide Dinitrate on Central Venous Pressure
Time frame: Baseline and 6 weeks
Effect of Isosorbide Dinitrate on Maximal Exercise Capacity VO2 Max
Time frame: Baseline and 6 weeks
Effect of Isosorbide Dinitrate on Maximal Exercise Capacity Heart Rate Response
Time frame: Baseline and 6 weeks
Effect of Isosorbide Dinitrate on Maximal Exercise Capacity Respiratory Rate Response
Time frame: Baseline and 6 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Sep 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37084132Bigelow AM, Riggs KW, Morales DLS, Opotowsky AR, Lubert AM, Dillman JR, Veldtman GR, Heydarian HC, Trout AT, Cooper DS, Goldstein SL, Chin C, Palermo JJ, Ollberding NJ, Mays WA, Alsaied T. Isosorbide DiNitrate Effect on Hemodynamic Profile, Liver Stiffness, and Exercise Tolerance in Fontan Circulation (The NEET Clinical Trial). Pediatr Cardiol. 2024 Oct;45(7):1389-1397. doi: 10.1007/s00246-023-03156-3. Epub 2023 Apr 21.
- Individual participant dataSharing planned: No
Related trials for Fontan
Not yet recruitingObservational study
A Simple Method for Monitoring the End-organ Function in Patients With Fontan Circulation.
Fontan Procedure, Fontan Circulation
RecruitingObservational study
Fontan Associated Liver Disease and the Evaluation of Biomarkers for Disease Severity Assessment
Congenital Heart Disease
RecruitingObservational study
Cholate Clearance in Fontan and Heart Failure
Fontan, Right Heart Failure
RecruitingObservational study
Pulmonary Determinants of Cardiorespiratory Fitness in Fontan Patients
Fontan Procedure, Congenital Heart Disease
RecruitingPhase 3
SGLT2 Inhibition With Empagliflozin in Fontan Circulatory Failure
Congenital Heart Disease
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Isosorbide Dinitrate in people with Fontan, run by Children's Hospital Medical Center, Cincinnati at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 Aug 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants Who Experience an Adverse Reaction to the Study Medication During the Study Enrollment Period. (time frame: Baseline and 6 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04297241, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Sep 2021.