Tadalafil Effects in Left Ventricle Diastolic Dysfunction in Resistant Hypertensive Patients

Hypertension Clinical Trial

Official title:

Phosphodiesterase-5 Inhibitor (Tadalafil) Two Weeks Administration Period Effects in Left Ventricle Diastolic Dysfunction and BNP Levels in Resistant Hypertensive Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01743911
• Other study ID #: CAAE 0044.0.146.000-09
• Secondary ID: [2009/53430-7]
• Status: Completed
• Phase: N/A
• First received: November 30, 2012
• Last updated: December 4, 2012
• Start date: September 2010
• Est. completion date: August 2012

Study information

• Verified date: December 2012
• Source: University of Campinas, Brazil
• Contact: n/a
• Is FDA regulated: No
• Health authority: Brazil: National Committee of Ethics in Research
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: August 2012
• Est. primary completion date: April 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 35 Years to 75 Years

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Single Blind (Subject), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hypertension

Intervention

Other:
• sugar pill
Sugar pills: 20mg orally, once a day for 2 weeks

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

Locations

Country	Name	City	State
Brazil	Laboratory of Cardiovascular Pharmacology - FCM - Unicamp	Campinas	São Paulo

Sponsors (2)

Lead Sponsor	Collaborator
University of Campinas, Brazil	Fundação de Amparo à Pesquisa do Estado de São Paulo

Country where clinical trial is conducted

Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Left Ventricle Diastolic Dysfunction	Outcome measurement assessed by Echocardiogram before and after a 2-week tadalafil administration period.	Baseline and 2 weeks	No
Secondary	Change in endothelial function	Outcome measure assessed by flow-mediated dilation before and after a 2-week tadalafil administration period.	baseline and 2 weeks	No
Secondary	Change in blood pressure levels	Blood pressure measurements assessed before and after a 2-week tadalafil administration period.	Baseline and 2 weeks	No
Secondary	Change in B-type Natriuretic Peptide (BNP-32) levels	Plasma brain natriuretic peptide (BNP-32)assessed before and after a 2-week tadalafil administration period	Baseline and 2 weeks	No
Secondary	Change in cyclic guanosine monophosphate (cGMP) levels	Cyclic guanosine monophosphate (cGMP) levels assessed before and after a 2-week tadalafil administration period	Baseline and 2 weeks	No
Secondary	Change in nitrite levels	Nitrite levels assessed before and after a 2-week tadalafil administration period.	Baseline and 2 weeks	No