FontanPhase 4NCT03965351
TRPV2 Agonists in the Fontan Circulation
A Phase 4 study testing Probenecid in people with Fontan, run by Children's Hospital Medical Center, Cincinnati at 1 site in United States.
Trial summary
There are currently very few proven pharmacologic options available for these patients. The recent discovery of transient receptor potential vanilloid (TRPV) channels, particularly TRPV2 channels, in the cardiovascular system is promising as a potential pathway for pharmacologic intervention for Fontan patients. Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Fontan
- What is being tested?
- Probenecid
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 8 participants
- Where
- 1 siteUnited States
- Study dates
- 21 Mar 2017to 31 Dec 2020
- Phase
- Phase 4
- 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 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- ≥ 12 years old
- Single ventricle congenital heart disease status post Fontan procedure.
- Impaired ventricular function as assessed by preexisting echocardiographic studies and any available MRI studies.
- LV inclusion criteria: Ejection fraction by cMRI or echo assessment of <50% or moderate to severe dysfunction.
- RV inclusion criteria: Ejection fraction by cMRI of <45% or moderate to severe dysfunction. Or, given the ASE recommendation to avoid use of 2-D imaging quantification for assessment of right ventricular systolic function, a peak global longitudinal strain value as assessed by a single reviewer with a value greater than -17% will also be included. Peak global longitudinal strain analysis will be performed for all eligible single right ventricles noted by subjective echo reports to have abnormal systolic function if no qualifying cardiac MRI assessment of ejection fraction is available.
Who cannot join
- Clinically unstable or ongoing illness.
- Evidence of untreated Fontan pathway obstruction.
- Presence of uncontrolled arrhythmias.
- Evidence of moderate or greater atrioventricular valve regurgitation.
- Pregnancy.
- History of sulfonamide allergy
Show all 15Show fewer
- Known G6PD deficiency
- Patients on certain drugs that have potentially dangerous interactions with probenecid: doripenem, zalcitabine, deferiperone, citalopram, methotrexate, ciprofloxacin, amoxicillin, cefprozil, cefpodoxime, cefotaxime, meropenem, ertapenem, valganciclovir, ganciclovir, ziovudine ketorolac, cefdinir, cephalexin, dapsone, indomethacin, and piperacillin.Each subject's medication list will be reviewed prior to study participation.
- Impaired renal function as defined by a GFR < 60mL/min/1.73 m2 within the last year.
- Patients at a higher risk for arrhythmia including those with a prior history of arrhythmia including atrial and ventricular dysrhythmia or those on established anti-arrhythmic therapy.
- Admission to the hospital due to a clinically significant arrhythmia within the previous month.
- Greater than moderate atrioventricular regurgitation as denoted on most recent echo report.
- Patients with atrio-pulmonary Fontan
- Currently enrolled in an interventional drug trial or completed an interventional drug trial within the past 30 days.
- Not appropriate for MRI screening due to having an implanted device.
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: TRPV2 Agonists in Fontan Circulation Patients
There are currently very few proven pharmacologic options available for these patients. The recent discovery of transient receptor potential vanilloid (TRPV) channels, particularly TRPV2 channels, in the cardiovascular system is promising as a potential pathway for pharmacologic intervention for Fontan patients. Probenecid, a drug best known as a treatment for gout or as a penicillin adjunct, acts as a TRPV2 agonist and has recently become the subject of study as a model therapy for the treatment of cardiomyopathy due to its positive inotropic and lusitropic effects. The purpose of this pilot study is to determine if probenecid will improve magnetic resonance (MRI) parameters of systolic and/or diastolic dysfunction as well as associated symptoms in patients with a Fontan circulation. The investigators will quantitatively assess functional improvement with pre- and post-treatment cardiopulmonary exercise testing.
- Conditions
- Fontan
- Being tested
- Probenecid, Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ProbenecidDrug
This is a cross-over pilot study where participants will receive both the study medication (probenecid), as well as a placebo to see if the study medication improves magnetic resonance parameters of systolic and diastolic dysfunction that occurs in the Fontan population.
PlaceboOther
placebo
| Study group | Role | What they receive |
|---|---|---|
| Probenecid | Experimental | the study medication (probenecid) as well as a placebo. Receives: Drug: Probenecid; Other: Placebo |
| Placebo | Placebo comparator | placebo compared to probenecid Receives: Drug: Probenecid; Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in End Diastolic and End Systolic Volume as Measured by Standard and Advanced MRI Parameters
Determine if Fontan patients treated with probenecid for four weeks will experience increased systolic and diastolic function (as measured via standard and advanced MRI parameters) compared with four weeks of placebo. Participants will be assigned to either the placebo arm or study medication arm for the first four weeks. They will then undergo a four week wash out period. Finally, participants will be placed into the study arm that they were not assigned to in the first four weeks when they return for the last four weeks of study participation. There will be four MRI scans over the course of the 12 week study period.
Measured: Total time participation in the study will be twelve weeks. Four weeks on the placebo or study medication, four weeks of a washout period and another four weeks with the study medication or placebo.
Secondary outcomes (5)
Changes in Exercise Performance (VO2 Absolute) as Determined by Completing Four Graded Exercise Tests Utilizing a Cycle Ergometer Ramp Protocol; Pre and Post Study Drug and Placebo Administration.
Determine if Fontan patients treated with probenecid for four weeks will experience improved exercise performance compared with four weeks of placebo as measured by a maximal graded exercise test. Participants will complete a graded maximal cycle ergometer test at each of their four study visits.
Measured: Total time participation in the study will be twelve weeks. Four weeks on the placebo or study medication, four weeks of a washout period and another four weeks with the study medication or placebo.
Impact of Study Medication on Exercise Capacity (Indexed VO2 [ml/kg/Min] of Single Ventricle Patients.
Determine if there is a quantitative difference in indexed VO2 max when patients have been taking the study medication (probenecid) versus a placebo.
Measured: Total time participation in the study will be twelve weeks. Four weeks on the placebo or study medication, four weeks of a washout period and another four weeks with the study medication or placebo.
Impact of Study Medication on the MRI Ejection Fraction of Single Ventricle Patients.
Determine if there is a quantitative difference in ejection fraction when patients are taking the study medication (probenecid) versus when they are taking a placebo.
Measured: Total time participation in the study will be twelve weeks. Four weeks on the placebo or study medication, four weeks of a washout period and another four weeks with the study medication or placebo.
Impact of Study Medication on MRI Flow Rates of the Ventricles (Cardiac Output) in Single Ventricle Patients
Determine if there is a quantitative difference in cardiac output of single ventricle patients when taking the study medication (probenecid) versus taking a placebo.
Measured: Total time participation in the study will be twelve weeks. Four weeks on the placebo or study medication, four weeks of a washout period and another four weeks with the study medication or placebo.
Impact of Study Medication on MRI Strain Values in Single Ventricle Patients
Determine if there is a quantitative difference in longitudinal, circumferential, and radial strain MRI values when subjects take the study medication (probenecid) versus a placebo.
Measured: Total time participation in the study will be twelve weeks. Four weeks on the placebo or study medication, four weeks of a washout period and another four weeks with the study medication or placebo.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 May 2019
- Study start21 Mar 2017
- Primary completion30 Jun 2020
- Study completion31 Dec 2020
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.
- 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Hospital Medical Center, Cincinnati
- Sponsor type
- University, hospital or other
- Collaborators
- American Heart Association
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03965351
- Sponsor's protocol ID
- 2017-0541
- Status last verified
- Jan 2021
- First submitted
- 16 May 2018
- Last updated
- 9 Jul 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 9 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- TRPV2 Agonists in Fontan Circulation Patients
- ClinicalTrials.gov ID
- NCT03965351
- Acronym / sponsor ID
- 2017-0541
- Conditions
- Fontan
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 8 participants (actual)
- Lead sponsor
- Children's Hospital Medical Center, CincinnatiUniversity, hospital or other
- Collaborators
- American Heart Association
- Study start
- 21 Mar 2017 (actual)
- Primary completion
- 30 Jun 2020 (actual)
- Study completion
- 31 Dec 2020 (actual)
- First posted
- 29 May 2019 (actual)
- Results
- Posted 9 Jul 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
There are currently very few proven pharmacologic options available for these patients. The recent discovery of transient receptor potential vanilloid (TRPV) channels, particularly TRPV2 channels, in the cardiovascular system is promising as a potential pathway for pharmacologic intervention for Fontan patients. Probenecid, a drug best known as a treatment for gout or as a penicillin adjunct, acts as a TRPV2 agonist and has recently become the subject of study as a model therapy for the treatment of cardiomyopathy due to its positive inotropic and lusitropic effects. The purpose of this pilot study is to determine if probenecid will improve magnetic resonance (MRI) parameters of systolic and/or diastolic dysfunction as well as associated symptoms in patients with a Fontan circulation. The investigators will quantitatively assess functional improvement with pre- and post-treatment cardiopulmonary exercise testing.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Probenecid | Experimental | Drug: Probenecid, Other: Placebothe study medication (probenecid) as well as a placebo. |
| Placebo | Placebo comparator | Drug: Probenecid, Other: Placeboplacebo compared to probenecid |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- ≥ 12 years old
- Single ventricle congenital heart disease status post Fontan procedure.
- Impaired ventricular function as assessed by preexisting echocardiographic studies and any available MRI studies.
Key exclusion criteria (15 listed)
- Clinically unstable or ongoing illness.
- Evidence of untreated Fontan pathway obstruction.
- Presence of uncontrolled arrhythmias.
- Evidence of moderate or greater atrioventricular valve regurgitation.
- Pregnancy.
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 |
|---|---|---|
| ProbenecidThis is a cross-over pilot study where participants will receive both the study medication (probenecid), as well as a placebo to see if the study medication improves magnetic resonance parameters of systolic and diastolic dysfunction that occurs in the Fontan population. | Drug | Placebo, Probenecid |
| Placeboplacebo | Other | Placebo, Probenecid |
Primary outcome
Changes in End Diastolic and End Systolic Volume as Measured by Standard and Advanced MRI Parameters
Time frame: Total time participation in the study will be twelve weeks. Four weeks on the placebo or study medication, four weeks of a washout period and another four weeks with the study medication or placebo.
Determine if Fontan patients treated with probenecid for four weeks will experience increased systolic and diastolic function (as measured via standard and advanced MRI parameters) compared with four weeks of placebo. Participants will be assigned to either the placebo arm or study medication arm for the first four weeks. They will then undergo a four week wash out period. Finally, participants will be placed into the study arm that they were not assigned to in the first four weeks when they return for the last four weeks of study participation. There will be four MRI scans over the course of the 12 week study period.
5 secondary outcomes
Changes in Exercise Performance (VO2 Absolute) as Determined by Completing Four Graded Exercise Tests Utilizing a Cycle Ergometer Ramp Protocol; Pre and Post Study Drug and Placebo Administration.
Time frame: Total time participation in the study will be twelve weeks. Four weeks on the placebo or study medication, four weeks of a washout period and another four weeks with the study medication or placebo.
Impact of Study Medication on Exercise Capacity (Indexed VO2 [ml/kg/Min] of Single Ventricle Patients.
Time frame: Total time participation in the study will be twelve weeks. Four weeks on the placebo or study medication, four weeks of a washout period and another four weeks with the study medication or placebo.
Impact of Study Medication on the MRI Ejection Fraction of Single Ventricle Patients.
Time frame: Total time participation in the study will be twelve weeks. Four weeks on the placebo or study medication, four weeks of a washout period and another four weeks with the study medication or placebo.
Impact of Study Medication on MRI Flow Rates of the Ventricles (Cardiac Output) in Single Ventricle Patients
Time frame: Total time participation in the study will be twelve weeks. Four weeks on the placebo or study medication, four weeks of a washout period and another four weeks with the study medication or placebo.
Impact of Study Medication on MRI Strain Values in Single Ventricle Patients
Time frame: Total time participation in the study will be twelve weeks. Four weeks on the placebo or study medication, four weeks of a washout period and another four weeks with the study medication or placebo.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jul 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Undecided
Related trials for Fontan
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A Simple Method for Monitoring the End-organ Function in Patients With Fontan Circulation.
Fontan Procedure, Fontan Circulation
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Fontan Associated Liver Disease and the Evaluation of Biomarkers for Disease Severity Assessment
Congenital Heart Disease
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Cholate Clearance in Fontan and Heart Failure
Fontan, Right Heart Failure
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Pulmonary Determinants of Cardiorespiratory Fitness in Fontan Patients
Fontan Procedure, Congenital Heart Disease
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SGLT2 Inhibition With Empagliflozin in Fontan Circulatory Failure
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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 4 study testing Probenecid 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 5 inclusion and 15 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 9 Jul 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. Some participants in this study may receive a placebo. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 9 Jul 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?
Changes in End Diastolic and End Systolic Volume as Measured by Standard and Advanced MRI Parameters (time frame: Total time participation in the study will be twelve weeks. Four weeks on the placebo or study medication, four weeks of a washout period and another four weeks with the study medication or placebo.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 9 Jul 2021.