Hypertension
Conditions
Keywords
blood pressure, inflammation, tumor Necrosis Factor-alpha
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.
Interventions
BIOLOGICALInfliximab
Monoclonal antibody biologic drug that inhibits tumour necrosis factor alpha (TNF-α), 3 mg/kg for 2 hours (250mL)
OTHERSaline
Saline for 2 hours (250mL)
Sponsors
University of Campinas, Brazil
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
35 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean blood pressure in mmHg | 15 minutes | Mean blood pressure will be simultaneously assessed for 15 minutes in baseline, during and post the infusions |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Endothelial function in percentage | Baseline 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/s | Baseline 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 |
| Cardiac hypertrophy in g/m² | Baseline 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 |
| Interleukin-6 | Baseline and post-1 week of the infusions | Plasma concentration of Interleukin-6 will be determined by ELISA |
| Interleukin-10 | Baseline and post-1 week of the infusions | Plasma concentration of Interleukin-10 will be determined by ELISA |
| Tumor necrosis factor-alpha in pg/mL | Baseline and post-1 week of the infusions | Plasma concentration of tumor necrosis factor-alpha will be determined by ELISA |
Countries
Brazil
Outcome results
None listed