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

Study Overview
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Brief Summary
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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
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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.

Official Title
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Effects of the TNF-alpha Inhibiton on Blood Pressure, Hemodynamic Parameters and Biomarkers in Resistant Hypertension

Conditions
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Hypertension

Intervention / Treatment
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* Biological: Infliximab
* Other: Saline


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: TNF-alpha inhibitor drug<br>Infliximab infusion (TNF-α inhibitor, 3 mg/kg, 250mL) | Biological: Infliximab<br>* Monoclonal antibody biologic drug that inhibits tumour necrosis factor alpha (TNF-α), 3 mg/kg for 2 hours (250mL)<br>* Other names: Tumour necrosis factor alpha (TNF-α) inhibitor;|
| Placebo Comparator: Placebo drug<br>Saline infusion (250mL) | Other: Saline<br>* Saline for 2 hours (250mL)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean blood pressure in mmHg | Mean blood pressure will be simultaneously assessed for 15 minutes in baseline, during and post the infusions | 15 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cardiac hypertrophy in g/m² | Left ventricular mass index will be determined by echocardiography in baseline and post-1 week of the infusions | Baseline and post-1 week of the infusions | 
| Endothelial function in percentage | Endothelial function will be assessed by flow-mediated dilation in baseline and post-1 week of the infusions | Baseline and post-1 week of the infusions | 
| Arterial stiffness in m/s | Arterial stiffness will be determined by pulse wave velocity in baseline and post-1 week of the infusions | Baseline and post-1 week of the infusions | 
| Tumor necrosis factor-alpha in pg/mL | Plasma concentration of tumor necrosis factor-alpha will be determined by ELISA | Baseline and post-1 week of the infusions | 
| Interleukin-6 | Plasma concentration of Interleukin-6 will be determined by ELISA | Baseline and post-1 week of the infusions | 
| Interleukin-10 | Plasma concentration of Interleukin-10 will be determined by ELISA | Baseline and post-1 week of the infusions | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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blood pressure, inflammation, tumor Necrosis Factor-alpha