Clinical trial NCT02743390: Effects of the TNF-alpha Inhibiton on Hemodynamic Parameters in Resistant Hypertension
Official title: Effects of the TNF-alpha Inhibiton on Blood Pressure, Hemodynamic Parameters and Biomarkers in Resistant Hypertension
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Hypertension
Keywords: blood pressure
inflammation
tumor Necrosis Factor-alpha
Lead sponsor: University of Campinas, Brazil
Sponsor class: OTHER
First posted: 2016-04-19
Enrollment: 10
Sex: ALL
Minimum age (years): 35
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Mean blood pressure in mmHg
timeFrame: 15 minutes
Secondary outcomes:
measure: Cardiac hypertrophy in g/m²
timeFrame: Baseline and post-1 week of the infusions
measure: Endothelial function in percentage
timeFrame: Baseline and post-1 week of the infusions
measure: Arterial stiffness in m/s
timeFrame: Baseline and post-1 week of the infusions
measure: Tumor necrosis factor-alpha in pg/mL
timeFrame: Baseline and post-1 week of the infusions
measure: Interleukin-6
timeFrame: Baseline and post-1 week of the infusions
measure: Interleukin-10
timeFrame: Baseline and post-1 week of the infusions
Other outcomes:
Locations:
city: Campinas
country: Brazil
facility: University of Campinas (UNICAMP)
state: São Paulo
Study officials:
affiliation: University of Campinas
name: Ana Paula Faria, PhD
role: STUDY_CHAIR
References: