Repurposing Probenecid as a Positive Inotrope for the Treatment of Heart Failure
- Conditions
- Systolic Heart Failure
- Interventions
- Drug: Placebo
- Registration Number
- NCT01814319
- Lead Sponsor
- University of Cincinnati
- Brief Summary
Probenecid is an FDA approved drug for the treatment gout and hyperuricemia. It has been used safely in humans for decades for this and other indications. The investigators have recently discovered that this drug can also stimulate other receptors in the heart and therefore improve its function. The hypothesis of this study is that probenecid can be used to improve the function of the heart and therefore the symptoms in patients with heart failure.
- Detailed Description
The investigators will test the hypothesis that oral administration of probenecid results in improved symptomatology and heart function in patients with systolic heart failure. There will be three cohorts.
Cohort 1 will enroll up to 50 subjects in a double-blinded, randomized, placebo-control, cross-over study with each patient serving as his or her own control. The subjects will have stable HF, an ejection fraction of less than or equal to 40% and NYHA II to IV symptoms. Each subject will undergo 1 week of investigational product (IP), consisting of oral probenecid therapy 1 gram twice a day or placebo with weekly follow.
The subjects will undergo EKGs, laboratory analysis, physical exams; dyspnea and quality of life questionnaires and a 6 minute walk test (MWT) at baseline. There will be 2 optional sub-studies one for echocardiographic data and the other biomarkers.
Cohort 2 will enroll up to 50 subjects in a double-blinded, randomized, placebo-control study and will include patients admitted to the hospital with acute decompensated HF. Each subject will also receive Investigational product consisting of either 1 gram orally twice daily of probenecid or placebo during their hospitalization. They will have daily follow-up with EKG and appropriate laboratory work. In addition to the EKG, laboratory analysis, physical exams, dyspnea and quality of life questionnaires and 6 MWT data will be collected; additional data such as length of hospital stay, biomarkers, use of inotropic therapy and diuretics, and rate of diuresis will also be collected.
Cohort 3 will enroll up to 50 healthy subjects in a double-blinded, randomized, placebo-control study. Each subject will also receive Investigational product consisting of either 2 grams orally of probenecid or placebo. During a 6 hour course subjects will have laboratory analysis, physical exam, telemetry, EKG and echocardiographic studies performed as measures of both safety and effect of the compound.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 20
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Probenecid Probenecid 1 gr oral twice daily Probenecid 1 gr oral twice daily or placebo will be given to the subject for 1 week (randomly assigned). A subsequent 1 week washout period will occur followed by the alternate therapy. placebo Placebo Probenecid 1 gr oral twice daily or placebo will be given to the subject for 1 week (randomly assigned). A subsequent 1 week washout period will occur followed by the alternate (placebo) therapy.
- Primary Outcome Measures
Name Time Method 6 minute walk test 1 week Measure for changes in the distance that the patient can walk over 6 minutes.
shortness of breath 1 week Measure objectively if there are changes in perceived shortness of breath using a standardized scale
- Secondary Outcome Measures
Name Time Method Ejection fraction 1 week We will measure via echocardiography the systolic function of the heart
beta naturietic peptide 1 week We will measure for changes in the beta natuiretic peptide as a marker of cardiac function and dilatation.
serum electrolytes 1 week We will measure several important electrolytes such as Na, K and Ca.
Trial Locations
- Locations (1)
University of Cincinnati
🇺🇸Cincinnati, Ohio, United States