Study to Determine How Cialis Effects the Renal Function in Response to Volume Expansion in Preclinical Diastolic Cardiomyopathy (Aim3)

• Status: Completed
• Trial end date: 2019-12-01
• Target enrollment: 0
• Participant gender: All

Summary

To determine the effect of 12 weeks of chronic PDEV inhibition with Tadalafil versus placebo on basal cardiorenal and humoral function and on the integrated cardiorenal and humoral response to acute sodium loading in subjects with preclinical Diastolic dysfunction (PDD) and renal (kidney) dysfunction

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Mayo Clinic
• Treatments: Tadalafil

Criteria

Inclusion Criteria:

• - Inclusion Criteria:

• A total of 39 patients with PDD as defined by an ejection fraction of greater than 50%, no clinical signs or symptoms of congestive heart failure, a minimal distance on 6-minute walk of equal or >450 meters will be recruited and calculated creatinine clearance of equal or less than 90 ml/min and greater than 30 ml/min, using the (MDRD-measurement of renal dysfunction, formula) assessed within the past 36 months. If the subject is not able to walk 450 meters due to pain in hips and knees and not fatigue or shortness of breath than they will still qualify for the protocol.

Exclusion Criteria:

• Current or anticipated future need for nitrate therapy

• Systolic blood pressure < 90 mmHg or > 180 mm Hg

• Diastolic blood pressure < 40 mmHg or > 100 mmHg

• Patients taking alpha antagonists or cytochrome P450 3A4 inhibitors (ketoconazole, itraconazole, erythromycin, saquinavir, cimetidine or serum proteases inhibitors for HIV) who cannot be taken off these medications for the duration of the study.

• Patients taking the following selective alpha blockers and who are unable to stop for the duration of the study;

• Alfuzosin

• Prazosin

• Doxazosin

• Tamsulosin

• Terazosin

• Silodosin

• Patients with retinitis pigmentosa, previous diagnosis of nonischemic optic neuropathy, untreated proliferative retinopathy or unexplained visual disturbance

• Patients with sickle cell anemia, multiple myeloma, leukemia or penile deformities placing them at risk for priapism (angulation, cavernosal fibrosis or Peyronie's disease)

• Patients with an allergy to iodine.

• Patients on PDEV inhibition for pulmonary hypertension

• Patients on PDEV inhibition for erectile dysfunction who are not willing to stop the medication for the duration of the study

• Valve disease (> moderate aortic or mitral stenosis; > moderate aortic or mitral regurgitation)

• Obstructive Hypertrophic cardiomyopathy

• Infiltrative or inflammatory myocardial disease (amyloid, sarcoid)

• Pericardial disease

• Have experienced a myocardial infarction or unstable angina, or have undergone percutaneous transluminal coronary angiography (PTCA) or coronary artery bypass grafting (CABG) within 60 days prior to consent, or requires either PTCA or CABG at the time of consent

• Severe congenital heart diseases

• Sustained ventricular tachycardia or ventricular fibrillation within 14 days of screening

• Second or third degree heart block without a permanent cardiac pacemaker

• Stroke within 3 months of screening or other evidence of significantly compromised Central Nervous System (CNS) perfusion

• Hemoglobin <9 g/dL

• Patients with severe liver disease (AST > 3x normal, alkaline phosphatase or bilirubin > 2x normal)

• Serum sodium of < 125 mEq/dL or > 150 mEq/dL

• Serum potassium of < 3.2 mEq/dL or > 5.9 mEq/dL

• Prior diagnosis of intrinsic renal diseases including renal artery stenosis of > 50%

• Peritoneal or hemodialysis within 90 days or anticipation that dialysis or ultrafiltration of any form will be required during the study period

• Less than 21 years of age

• Pregnant or nursing women.

• Women of child bearing potential who do not have a negative pregnancy test at study entry and who are not using effective contraception

• Non-cardiac condition limiting life expectancy to less than one year, per physician judgment

• Other acute or chronic medical conditions or laboratory abnormality which may increase the risks associated with study participation or may interfere with interpretation of the data

• Received an investigational drug within 1 month prior to dosing

• In the opinion of the investigator is unlikely to comply with the study protocol or is unsuitable for any reasons