Tadalafil Effects in Left Ventricle Diastolic Dysfunction in Resistant Hypertensive Patients
Left ventricle diastolic dysfunction (LVDD) is associated with resistant hypertension. In addition, brain natriuretic peptide (BNP) levels are elevated when LVDD is present. It has been shown that phosphodiesterase-5 (PDE5) inhibition improves left ventricle diastolic function in hypertensive rats, despite any difference in blood pressure levels. Also, left ventricle diastolic function enhancement reduces BNP concentration in hypertensive patients. However, it is unknown if these effects exists in humans with resistant hypertension. Therefore, this study was developed to evaluate if the use of a PDE5 inhibitor (tadalafil) for 2 weeks improves LVDD and its effects in BNP levels in resistant hypertensive patients.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
|Official Title:||Phosphodiesterase-5 Inhibitor (Tadalafil) Two Weeks Administration Period Effects in Left Ventricle Diastolic Dysfunction and BNP Levels in Resistant Hypertensive Patients|
- Change in Left Ventricle Diastolic Dysfunction [ Time Frame: Baseline and 2 weeks ] [ Designated as safety issue: No ]Outcome measurement assessed by Echocardiogram before and after a 2-week tadalafil administration period.
- Change in endothelial function [ Time Frame: baseline and 2 weeks ] [ Designated as safety issue: No ]Outcome measure assessed by flow-mediated dilation before and after a 2-week tadalafil administration period.
- Change in blood pressure levels [ Time Frame: Baseline and 2 weeks ] [ Designated as safety issue: No ]Blood pressure measurements assessed before and after a 2-week tadalafil administration period.
- Change in B-type Natriuretic Peptide (BNP-32) levels [ Time Frame: Baseline and 2 weeks ] [ Designated as safety issue: No ]Plasma brain natriuretic peptide (BNP-32)assessed before and after a 2-week tadalafil administration period
- Change in cyclic guanosine monophosphate (cGMP) levels [ Time Frame: Baseline and 2 weeks ] [ Designated as safety issue: No ]Cyclic guanosine monophosphate (cGMP) levels assessed before and after a 2-week tadalafil administration period
- Change in nitrite levels [ Time Frame: Baseline and 2 weeks ] [ Designated as safety issue: No ]Nitrite levels assessed before and after a 2-week tadalafil administration period.
|Study Start Date:||September 2010|
|Study Completion Date:||August 2012|
|Primary Completion Date:||April 2012 (Final data collection date for primary outcome measure)|
Placebo Comparator: sugar pill
Intervention: sugar pill
Other: sugar pill
Sugar pills: 20mg orally, once a day for 2 weeks
Other Name: No brand name.
Active Comparator: tadalafil
Tadalafil pills: 20mg orally, once a day for 2 weeks.
Other Name: Cialis, Lilly, USA
Resistant hypertensive patients have a high incidence of left ventricle diastolic dysfunction (LVDD). Lowering blood pressure levels improves diastolic function, however, there is no proved effective treatment specifically for this disease. Studies in hypertensive rats have shown presence of phosphodiesterase-5 in cardiac cells and an improvement in left ventricle diastolic function using a phosphodiesterase-5 (PDE5) inhibitor, the sildenafil. PDE5 has also been demonstrated in human heart cells with cardiac disease. In addition, LVDD is associated with high levels of brain natriuretic peptide (BNP), which reduces with diastolic function improvement. Therefore, it is reasonable to suppose that PDE-5 inhibitor use in humans with LVDD and resistant hypertension could improve diastolic function. Objective: Evaluate the chronic effect of a PDE-5 inhibitor on LVDD and BNP levels in resistant hypertensive patients. Casuistic and methods: 20 resistant hypertensive patients with LVDD types I and II will be evaluated with echocardiography study, ambulatory blood pressure monitoring (ABPM), office blood pressure measurements, endothelial function analysis using the brachial artery flow mediation dilation technique (FMD) and BNP plasma levels. Then, the subjects will receive oral placebo for 2 weeks. After this period, the same exams will be repeated. Two weeks later, the protocol will be performed again to the same 20 patients, using tadalafil (the longest half-life PDE-5 inhibitor) 20mg orally instead of the placebo. Hypothesis: investigators hypothesize that the use of tadalafil will improve left ventricle diastolic function with BNP reduced levels and this effect will be independent of blood pressure decrease or endothelial function improvement.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01743911
|Laboratory of Cardiovascular Pharmacology - FCM - Unicamp|
|Campinas, São Paulo, Brazil, 13083-970|
|Principal Investigator:||Heitor Moreno-Junior, MD, PhD||Faculty of Medical Sciences - Unicamp|