Effects of Sildenafil in Resistant Hypertensives and Genetic Polymorphism

NCT ID: NCT01392638

Last Updated: 2012-10-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-07-31
• Study Completion Date: 2012-09-30

Brief Summary

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.

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.

Conditions

Hypertension

Keywords

Sildenafil; Nitric oxide synthase; Polymorphism; Hemodynamics

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

sugar pill

Intervention: sugar pill

Group Type: PLACEBO_COMPARATOR

sugar pill

Intervention Type: OTHER

Sugar pills: 37.5, 50.0, and 100.0 mg each 30 minutes.

sildenafil

Intervention: sildenafil citrate

Group Type: ACTIVE_COMPARATOR

sildenafil

Intervention Type: DRUG

Sildenafil pills: 37.5, 50.0, and 100.0 mg each 30 minutes.

Interventions

sugar pill

Sugar pills: 37.5, 50.0, and 100.0 mg each 30 minutes.

Intervention Type: OTHER

sildenafil

Sildenafil pills: 37.5, 50.0, and 100.0 mg each 30 minutes.

Intervention Type: DRUG

Other Intervention Names

No brand name.; Viagra, Pfizzer Lab., USA

Eligibility 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

• Minimum Eligible Age: 35 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fundação de Amparo à Pesquisa do Estado de São Paulo

OTHER_GOV

Sponsor Role: collaborator

University of Campinas, Brazil

OTHER

Sponsor Role: lead

Responsible Party

Heitor Moreno Junior

MD. PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Heitor Moreno, PhD

Role: PRINCIPAL_INVESTIGATOR

Faculty of Medical Sciences - Unicamp

Locations

Laboratory of Cardiovascular Pharmacology - FCM - Unicamp

Campinas, São Paulo, Brazil

Countries

Brazil

Other Identifiers

FAPESP

Identifier Type: OTHER

Identifier Source: secondary_id

CAAE-0758.0.146.000-09

Identifier Type: -

Identifier Source: org_study_id