Clinical trial NCT01743911: Tadalafil Effects in Left Ventricle Diastolic Dysfunction in Resistant Hypertensive Patients
Official title: Phosphodiesterase-5 Inhibitor (Tadalafil) Two Weeks Administration Period Effects in Left Ventricle Diastolic Dysfunction and BNP Levels in Resistant Hypertensive Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Hypertension
Keywords: Tadalafil
Resistant Hypertension
Left Ventricle Diastolic Dysfunction
Brain natriuretic peptide
Lead sponsor: University of Campinas, Brazil
Sponsor class: OTHER
Collaborators: name: Fundação de Amparo à Pesquisa do Estado de São Paulo
First posted: 2012-12-06
Enrollment: 20
Sex: ALL
Minimum age (years): 35
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Exclusion Criteria:

* valvulopathy
* decompensated heart failure
* important cardiac arrhythmias
* nephropathy
* hepatopathy
* autoimmune disease
* tabagism
* decompensated diabetes
* uncontrolled dislipidemia

Primary outcomes:
measure: Change in Left Ventricle Diastolic Dysfunction
timeFrame: Baseline and 2 weeks
Secondary outcomes:
measure: Change in endothelial function
timeFrame: baseline and 2 weeks
measure: Change in blood pressure levels
timeFrame: Baseline and 2 weeks
measure: Change in B-type Natriuretic Peptide (BNP-32) levels
timeFrame: Baseline and 2 weeks
measure: Change in cyclic guanosine monophosphate (cGMP) levels
timeFrame: Baseline and 2 weeks
measure: Change in nitrite levels
timeFrame: Baseline and 2 weeks
Other outcomes:
Locations:
city: Campinas
country: Brazil
facility: Laboratory of Cardiovascular Pharmacology - FCM - Unicamp
state: São Paulo
Study officials:
affiliation: Faculty of Medical Sciences - Unicamp
name: Heitor Moreno-Junior, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: