Tadalafil Effects in Left Ventricle Diastolic Dysfunction in Resistant Hypertensive Patients

This study has been completed.
Sponsor:
Collaborator:
Fundação de Amparo à Pesquisa do Estado de São Paulo
Information provided by (Responsible Party):
Heitor Moreno Junior, University of Campinas, Brazil
ClinicalTrials.gov Identifier:
NCT01743911
First received: November 30, 2012
Last updated: December 4, 2012
Last verified: December 2012
  Purpose

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 Intervention
Hypertension
Other: sugar pill
Drug: Tadalafil

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by University of Campinas, Brazil:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Enrollment: 20
Study Start Date: September 2010
Study Completion Date: August 2012
Primary Completion Date: April 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Intervention: tadalafil
Drug: Tadalafil
Tadalafil pills: 20mg orally, once a day for 2 weeks.
Other Name: Cialis, Lilly, USA

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

Ages Eligible for Study:   35 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01743911

Locations
Brazil
Laboratory of Cardiovascular Pharmacology - FCM - Unicamp
Campinas, São Paulo, Brazil, 13083-970
Sponsors and Collaborators
University of Campinas, Brazil
Fundação de Amparo à Pesquisa do Estado de São Paulo
Investigators
Principal Investigator: Heitor Moreno-Junior, MD, PhD Faculty of Medical Sciences - Unicamp
  More Information

No publications provided

Responsible Party: Heitor Moreno Junior, MD, PhD., University of Campinas, Brazil
ClinicalTrials.gov Identifier: NCT01743911     History of Changes
Other Study ID Numbers: CAAE 0044.0.146.000-09, [2009/53430-7]
Study First Received: November 30, 2012
Last Updated: December 4, 2012
Health Authority: Brazil: National Committee of Ethics in Research

Keywords provided by University of Campinas, Brazil:
Tadalafil
Resistant Hypertension
Left Ventricle Diastolic Dysfunction
Brain natriuretic peptide

Additional relevant MeSH terms:
Hypertension
Vascular Diseases
Cardiovascular Diseases
Tadalafil
Phosphodiesterase 5 Inhibitors
Vasodilator Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Urological Agents

ClinicalTrials.gov processed this record on September 30, 2014