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Tadalafil Effects in Left Ventricle Diastolic Dysfunction in Resistant Hypertensive Patients

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ClinicalTrials.gov Identifier: NCT01743911
Recruitment Status : Completed
First Posted : December 6, 2012
Last Update Posted : December 6, 2012
Information provided by (Responsible Party):

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
Hypertension Other: sugar pill Drug: Tadalafil

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  (Clinical Trial)
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 : September 2010
Primary Completion Date : April 2012
Study Completion Date : August 2012

Resource links provided by the National Library of Medicine

Drug Information available for: Tadalafil
U.S. FDA Resources

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 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

Outcome Measures

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

Secondary Outcome Measures :
  1. Change in endothelial function [ Time Frame: baseline and 2 weeks ]
    Outcome measure assessed by flow-mediated dilation before and after a 2-week tadalafil administration period.

  2. Change in blood pressure levels [ Time Frame: Baseline and 2 weeks ]
    Blood pressure measurements assessed before and after a 2-week tadalafil administration period.

  3. Change in B-type Natriuretic Peptide (BNP-32) levels [ Time Frame: Baseline and 2 weeks ]
    Plasma brain natriuretic peptide (BNP-32)assessed before and after a 2-week tadalafil administration period

  4. Change in cyclic guanosine monophosphate (cGMP) levels [ Time Frame: Baseline and 2 weeks ]
    Cyclic guanosine monophosphate (cGMP) levels assessed before and after a 2-week tadalafil administration period

  5. Change in nitrite levels [ Time Frame: Baseline and 2 weeks ]
    Nitrite levels assessed before and after a 2-week tadalafil administration period.

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   35 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01743911

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
Principal Investigator: Heitor Moreno-Junior, MD, PhD Faculty of Medical Sciences - Unicamp
More Information

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] ( Other Identifier: FAPESP )
First Posted: December 6, 2012    Key Record Dates
Last Update Posted: December 6, 2012
Last Verified: December 2012

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

Additional relevant MeSH terms:
Vascular Diseases
Cardiovascular Diseases
Phosphodiesterase 5 Inhibitors
Vasodilator Agents
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Urological Agents