Effects of Sildenafil in Resistant Hypertensives and Genetic Polymorphism

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:
NCT01392638
First received: January 25, 2011
Last updated: October 29, 2012
Last verified: October 2012
  Purpose

Sildenafil citrate slightly reduces blood pressure in treated hypertensives patients. However, it is unknown if the simultaneous use of sildenafil plus, at least, 3 classes of antihypertensive agents in patients with resistant arterial hypertension may have a synergic effect on the patients blood pressure. Moreover, sildenafil improves the endogen nitric oxide effects. The nitric oxide is an important signaling molecule in the body that contributes to vessel homeostasis by inhibiting vascular smooth muscle contraction and growth. Hypertension often impaired NO pathways. Nitric oxide is produced by an enzyme, called nitric oxide synthase (NOS3), that show some genetics variants, which means that this enzyme can be different from person to person. Therefore, the objective of the present study is to examine the influence of a genetic variant (known to affect NOS3 levels) in sildenafil acute effects on hemodynamic and cardiovascular function. The investigators hypothesis is that individuals with the genetic variant associated to higher levels of NOS3 will have more benefits from sildenafil treatment.


Condition Intervention
Hypertension
Other: sugar pill
Drug: sildenafil

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: Influence of the Nitric Oxide Synthase T-786C Polymorphism on the Response to Acute Inhibition of Phosphodiesterase 5 in Resistant Hypertension

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Cardiac Output, total peripheral resistance, mean arterial pressure [ Time Frame: Each 30 minutes ] [ Designated as safety issue: No ]
    Hemodynamic measures each 30 minutes


Secondary Outcome Measures:
  • Left ventricular diastolic function parameters, endothelial function [ Time Frame: Pre- and post-sildenafil accumulated doses ] [ Designated as safety issue: No ]
    Assessment of how hemodynamic changes determined by sildenafil would affect endothelial and left ventricular diastolic parameters.


Enrollment: 120
Study Start Date: July 2010
Study Completion Date: September 2012
Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: sugar pill
Intervention: sugar pill
Other: sugar pill
Sugar pills: 37.5, 50.0, and 100.0 mg each 30 minutes.
Other Name: No brand name.
Active Comparator: sildenafil
Intervention: sildenafil citrate
Drug: sildenafil
Sildenafil pills: 37.5, 50.0, and 100.0 mg each 30 minutes.
Other Name: Viagra, Pfizzer Lab., USA

Detailed Description:

Endothelial dysfunction is one of the mechanisms involved in the maintenance of the high blood pressure levels in resistants hypertensives patients, which is directly related to the NO-GMPc pathway. The phosphodiesterase 5 inhibitor, sildenafil citrate, slightly reduces systolic and diastolic blood pressures in treated hypertensives patients. However, it is unknown if the simultaneous use of sildenafil plus, at least, 3 classes of antihypertensive agents in patients with resistant arterial hypertension may have a synergic effect on the patients blood pressure. Moreover, sildenafil improves the endogen nitric oxide effects produced by eNOS. Therefore, since the genetics polymorphisms of eNOS can affect the NO tissue levels, it seems reasonable to suppose that the acute effects of sildenafil may be modulated by them. Objective: To examine the influence of the T-786C polymorphism of eNOS gene in sildenafil acute effects on hemodynamic and cardiovascular function in resistant hypertensives patients. Casuistics and Methods: Around 120 patients with HAR will be genotyped for the T-786C eNOS polymorphism, from which the investigators will enroll in this study 15 patients with TT genotype and 15 patients with CC genotype. The patients will be monitored with the Portapres system (non-invasive hemodynamic). After basal records of the studied variables, increasing doses of sildenafil will be administrated (37.5, 50.0 e 100.0 mg). Five minutes before each new dose, the studied variables will be recorded again. Hypothesis: The investigators hypothesize that the sildenafil, besides the anti-ischemic effect, will improve the patients hemodynamic status and, moreover, that it will occur a modulation of this effect by the T-786C polymorphism.

  Eligibility

Ages Eligible for Study:   35 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • resistant hypertensive (according to Resistant Hypertension - AHA Statement - 2008);
  • compliance with antihypertensive treatment;
  • age >35 years;
  • diastolic dysfunction

Exclusion Criteria:

  • valvulopathy
  • decompensated heart failure
  • important cardiac arrhythmias
  • nephropathy
  • hepatopathy
  • autoimmune disease
  • tabagism
  • decompensated diabetes
  • uncontrolled dislipidemia
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01392638

Locations
Brazil
Laboratory of Cardiovascular Pharmacology - FCM - Unicamp
Campinas, SP, Brazil
Sponsors and Collaborators
University of Campinas, Brazil
Fundação de Amparo à Pesquisa do Estado de São Paulo
Investigators
Principal Investigator: Heitor Moreno, 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: NCT01392638     History of Changes
Other Study ID Numbers: CAAE-0758.0.146.000-09, FAPESP
Study First Received: January 25, 2011
Last Updated: October 29, 2012
Health Authority: Brazil: National Committee of Ethics in Research

Keywords provided by University of Campinas, Brazil:
Sildenafil
Nitric oxide synthase
Polymorphism
Hemodynamics

Additional relevant MeSH terms:
Hypertension
Vascular Diseases
Cardiovascular Diseases
Nitric Oxide
Sildenafil
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Asthmatic Agents
Respiratory System Agents
Therapeutic Uses
Free Radical Scavengers
Antioxidants
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Endothelium-Dependent Relaxing Factors
Vasodilator Agents
Cardiovascular Agents
Protective Agents
Phosphodiesterase 5 Inhibitors
Phosphodiesterase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on April 15, 2014