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

Hypertension Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02743390
• Other study ID #: 2015171517
• Status: Completed
• Phase: Phase 4
• First received: April 5, 2016
• Last updated: November 7, 2017
• Start date: March 2015
• Est. completion date: July 2017

Study information

• Verified date: November 2017
• Source: University of Campinas, Brazil
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: July 2017
• Est. primary completion date: July 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 35 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Hypertension

Intervention

Biological:
• Infliximab
Monoclonal antibody biologic drug that inhibits tumour necrosis factor alpha (TNF-a), 3 mg/kg for 2 hours (250mL)

Other:
• Saline
Saline for 2 hours (250mL)

Locations

Country	Name	City	State
Brazil	University of Campinas (UNICAMP)	Campinas	São Paulo

Sponsors (1)

Lead Sponsor	Collaborator
University of Campinas, Brazil

Country where clinical trial is conducted

Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Interleukin-6	Plasma concentration of Interleukin-6 will be determined by ELISA	Baseline and post-1 week of the infusions
Secondary	Interleukin-10	Plasma concentration of Interleukin-10 will be determined by ELISA	Baseline and post-1 week of the infusions