Intervention: Tadalafil
Trial phase: Phase 1 | Phase 2
ATC code: C02KX52 | C02KX54 | G04BE08 | G04CA54 | G04CB51
SMILES: [H][C@]12Cc3c([nH]c4ccccc34)[C@@H](c3ccc4c(c3)OCO4)N1C(=O)CN(C)C2=O
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 15
Group description: Subject received Tadalafil daily for a total of 12 weeks

Tadalafil: Tadalafil 5 mg tablet. Daily. Tadalafil dose varies from 5 mg to 20 mg for 12 weeks. If blood pressure is >95 then subject dismissed from the Clinical Research Unit (CRU) on 2 (5 mg) tabs of tadalafil or placebo. If blood pressure is between 90 - 95 mmHg systolic, then dismiss on 1 (5 mg) tab of Tadalafil.

At 2 weeks (± 5 days) if blood pressure is> 100 than add 1 (5 mg) tab of Tadalafil to make a total of 3 (5mg) tabs of Tadalafil.

At 4 weeks(± 5 days) if blood pressure is > 100 add 1 (5 mg) tab to make a total of 4 (5 mg) tablets of Tadalafil.
Eligibility 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