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Effects of the TNF-alpha Inhibiton on Hemodynamic Parameters in Resistant Hypertension

Phase 4
Completed
Conditions
Hypertension
Interventions
Biological: Infliximab
Other: Saline
Registration Number
NCT02743390
Lead Sponsor
University of Campinas, Brazil
Brief Summary

Resistant hypertension (RH) is characterized by high blood pressure (BP) in spite of concurrent use of three or more antihypertensive agents of different classes, combined at optimal doses. Currently it has been largely discussed the influence of inflammation in RH. The BP variation promotes increased expression of pro-inflammatory cytokines, such as tumor necrosis factor-alpha, interleukins 1 and 6. It was showed that treatment with TNF-α inhibitor improves BP and endothelial function, and reduces arterial stiffness in patients with rheumatoid arthritis. Recently, it was demonstrated that TNF-α levels are increased in RH subjects compared to normotensives. This study aims to assess whether the acute inhibition of TNF-α changes hemodynamic parameters, such as mean BP levels in RH.

Detailed Description

This crossover, double-blind study will include 12 resistant hypertensive subjects - regularly followed at the Outpatient Resistant Hypertension Clinic/UNICAMP - which will randomized assigned to (1) saline infusion followed by infliximab infusion (TNF-α inhibitor, 3 mg/kg) and (2) infliximab followed by saline, for two hours and washout of the 40-day period between both infusions. It is expected that the TNF-α inhibition regulates hemodynamic parameters, such as mean BP, cardiac Output, total peripheral resistance, which may allow a better rational approach for the RH treatment.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
10
Inclusion Criteria
  • the diagnosis recommended by the AHA Statment on Resistant Hypertension (2008)
  • a 6-month period clinic follow-up
  • give written informed consent form
Exclusion Criteria
  • secondary Hypertension
  • pseudoresistance hypertension (poor medication adherence and white coat hypertension)
  • patients with symptomatic ischemic heart disease, impaired renal function, liver disease and history of stroke, myocardial infarction and peripheral vascular diseases
  • pregnant women
  • smoking
  • autoimmune diseases

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
TNF-alpha inhibitor drugInfliximabInfliximab infusion (TNF-α inhibitor, 3 mg/kg, 250mL)
Placebo drugSalineSaline infusion (250mL)
Primary Outcome Measures
NameTimeMethod
Mean blood pressure in mmHg15 minutes

Mean blood pressure will be simultaneously assessed for 15 minutes in baseline, during and post the infusions

Secondary Outcome Measures
NameTimeMethod
Cardiac hypertrophy in g/m²Baseline and post-1 week of the infusions

Left ventricular mass index will be determined by echocardiography in baseline and post-1 week of the infusions

Endothelial function in percentageBaseline and post-1 week of the infusions

Endothelial function will be assessed by flow-mediated dilation in baseline and post-1 week of the infusions

Arterial stiffness in m/sBaseline and post-1 week of the infusions

Arterial stiffness will be determined by pulse wave velocity in baseline and post-1 week of the infusions

Tumor necrosis factor-alpha in pg/mLBaseline and post-1 week of the infusions

Plasma concentration of tumor necrosis factor-alpha will be determined by ELISA

Interleukin-6Baseline and post-1 week of the infusions

Plasma concentration of Interleukin-6 will be determined by ELISA

Interleukin-10Baseline and post-1 week of the infusions

Plasma concentration of Interleukin-10 will be determined by ELISA

Trial Locations

Locations (1)

University of Campinas (UNICAMP)

🇧🇷

Campinas, São Paulo, Brazil

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