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

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

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.

Study Overview

• Status: Completed
• Conditions: Hypertension
• Intervention / Treatment: Biological: Infliximab; Other: Saline

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.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 4

Contacts and Locations

Study Locations

• Brazil
  • São Paulo
    • Campinas, São Paulo, Brazil, 13083970
      • University of Campinas (UNICAMP)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: TNF-alpha inhibitor drug; Infliximab infusion (TNF-α inhibitor, 3 mg/kg, 250mL)	Biological: Infliximab; Monoclonal antibody biologic drug that inhibits tumour necrosis factor alpha (TNF-α), 3 mg/kg for 2 hours (250mL); Other Names: Tumour necrosis factor alpha (TNF-α) inhibitor
PLACEBO_COMPARATOR: Placebo drug; Saline infusion (250mL)	Other: Saline; Saline for 2 hours (250mL)

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Campinas, Brazil
• Investigators: Study Chair: Ana Paula Faria, PhD, University of Campinas

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 1, 2015
• Primary Completion (ACTUAL): July 1, 2017
• Study Completion (ACTUAL): July 1, 2017

Study Registration Dates

• First Submitted: April 5, 2016
• First Submitted That Met QC Criteria: April 18, 2016
• First Posted (ESTIMATE): April 19, 2016

Study Record Updates

• Last Update Posted (ACTUAL): November 9, 2017
• Last Update Submitted That Met QC Criteria: November 7, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Keywords: blood pressure; inflammation; tumor Necrosis Factor-alpha
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension; Antirheumatic Agents; Gastrointestinal Agents; Dermatologic Agents; Infliximab
• Other Study ID Numbers: 2015171517

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED