Tadalafil Effects in Left Ventricle Diastolic Dysfunction in Resistant Hypertensive Patients

Sponsor

University of Campinas, Brazil (Other)

Overall Status

Completed

CT.gov ID

NCT01743911

Collaborator

Fundação de Amparo à Pesquisa do Estado de São Paulo (Other)

Enrollment

Location

Arms

Duration (Months)

0.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Hypertension	Other: sugar pill Drug: Tadalafil	N/A

Detailed Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

20 participants

Allocation:

Non-Randomized

Intervention Model:

Crossover Assignment

Masking:

Single (Participant)

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

Study Start Date :

Sep 1, 2010

Actual Primary Completion Date :

Apr 1, 2012

Actual Study Completion Date :

Aug 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: sugar pill Intervention: sugar pill	Other: sugar pill Sugar pills: 20mg orally, once a day for 2 weeks Other Names: No brand name.
Active Comparator: tadalafil Intervention: tadalafil	Drug: Tadalafil Tadalafil pills: 20mg orally, once a day for 2 weeks. Other Names: Cialis, Lilly, USA

Arm

Intervention/Treatment

Placebo Comparator: sugar pill

Intervention: sugar pill

Other: sugar pill

Sugar pills: 20mg orally, once a day for 2 weeks

Other Names:

No brand name.

Active Comparator: tadalafil

Intervention: tadalafil

Drug: Tadalafil

Tadalafil pills: 20mg orally, once a day for 2 weeks.

Other Names:

Cialis, Lilly, USA

Outcome Measures

Primary Outcome Measures

Change in Left Ventricle Diastolic Dysfunction [Baseline and 2 weeks]
Outcome measurement assessed by Echocardiogram before and after a 2-week tadalafil administration period.

Secondary Outcome Measures

Change in endothelial function [baseline and 2 weeks]
Outcome measure assessed by flow-mediated dilation before and after a 2-week tadalafil administration period.
Change in blood pressure levels [Baseline and 2 weeks]
Blood pressure measurements assessed before and after a 2-week tadalafil administration period.
Change in B-type Natriuretic Peptide (BNP-32) levels [Baseline and 2 weeks]
Plasma brain natriuretic peptide (BNP-32)assessed before and after a 2-week tadalafil administration period
Change in cyclic guanosine monophosphate (cGMP) levels [Baseline and 2 weeks]
Cyclic guanosine monophosphate (cGMP) levels assessed before and after a 2-week tadalafil administration period
Change in nitrite levels [Baseline and 2 weeks]
Nitrite levels assessed before and after a 2-week tadalafil administration period.

Eligibility Criteria

Criteria

Ages Eligible for Study:

35 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

resistant hypertension (according to Resistant Hypertension - American Heart Association Statement - 2008);
compliance with antihypertensive treatment;
age >35 years;
left ventricle diastolic dysfunction types I and II