Neuroinflammation in Hypertension Study (MINIHT)

The Role of Neuroinflammation in Hypertension.Minocycline for Resistant Hypertension: a Randomized Double Blind Placebo-Controlled Trial

To demonstrate that in patients with resistant hypertension oral treatment with minocycline via inhibition of central immune cell activation and inflammation results in reduced central sympathetic outflow and concomitant lowering of BP.

Study Overview

• Status: Recruiting
• Conditions: Resistant Hypertension
• Intervention / Treatment: Drug: Minocycline

Detailed Description

This is a randomized, double-blind, placebo controlled, parallel group design study aiming to compare the effects of minocycline 100mg twice daily vs matched placebo for 12 weeks on ambulatory BP and the parameters of sympathetic and immune activation

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Revathy Carnagarin, MD; Phone Number: +61892240316; Email: revathy.carnagarin@uwa.edu.au
• Study Contact Backup: Name: Omar Azzam, MD; Phone Number: +61892242244; Email: omar.azzam@health.wa.gov.au

Study Locations

• Australia
  • Western Australia
    • Perth, Western Australia, Australia, 6000
      • Recruiting
      • Royal Perth Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Aged: 45 -65 years
• Signed informed consent
• Clinical diagnosis of Resistant Hypertension
• Daytime systolic ambulatory BP >135mmHg.

Exclusion Criteria:• eGFR of <45 mL/min/1.73m2

• History of myocardial infarction (MI) or any cardiovascular event within 3 months of screening period, clinically significant AV conduction disturbances and/or arrhythmias,
• current of past history of heart failure (LVEF ≤40%)
• psychotropic agents, antidepressants and NSAIDS
• alcohol consumption of >3 standard drinks.
• known hypersensitivity or contraindication to minocycline or other tetracyclines.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Minocycline Group; Subjects will be randomized to receive Minocycline 100mg twice daily	Drug: Minocycline; Participants will be randomly assigned to receive either Minocycline 100mg twice daily or Placebo. Comprehensive testing will be performed at baseline, and at the end of the 12 week intervention phase.; Other Names: Akamin
PLACEBO_COMPARATOR: Placebo Group; Subjects will be randomized to receive placebo.	Drug: Minocycline; Participants will be randomly assigned to receive either Minocycline 100mg twice daily or Placebo. Comprehensive testing will be performed at baseline, and at the end of the 12 week intervention phase.; Other Names: Akamin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The difference in the daytime systolic blood pressure between groups after respective treatment.	Office and ambulatory blood pressures	12 weeks
Assessment of change in central and peripheral inflammation	FDG PET	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in muscle sympathetic nerve activity	Muscle sympathetic nerve activity assessed by microneurography	12 weeks
Change in central Blood Pressure	central Blood Pressure assessed by Sphygmocor XCEL	12 weeks

Collaborators and Investigators

• Sponsor: Royal Perth Hospital
• Investigators: Principal Investigator: Markus Schlaich, MD, University of Western Australia and Royal Perth Hospital

Publications and helpful links

General Publications

• Carnagarin R, Matthews V, Zaldivia MTK, Peter K, Schlaich MP. The bidirectional interaction between the sympathetic nervous system and immune mechanisms in the pathogenesis of hypertension. Br J Pharmacol. 2019 Jun;176(12):1839-1852. doi: 10.1111/bph.14481. Epub 2018 Sep 25.
• Santisteban MM, Ahmari N, Carvajal JM, Zingler MB, Qi Y, Kim S, Joseph J, Garcia-Pereira F, Johnson RD, Shenoy V, Raizada MK, Zubcevic J. Involvement of bone marrow cells and neuroinflammation in hypertension. Circ Res. 2015 Jul 3;117(2):178-91. doi: 10.1161/CIRCRESAHA.117.305853. Epub 2015 May 11.

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 2, 2020
• Primary Completion (ANTICIPATED): August 1, 2024
• Study Completion (ANTICIPATED): February 1, 2025

Study Registration Dates

• First Submitted: July 10, 2020
• First Submitted That Met QC Criteria: July 16, 2020
• First Posted (ACTUAL): July 20, 2020

Study Record Updates

• Last Update Posted (ACTUAL): September 29, 2022
• Last Update Submitted That Met QC Criteria: September 28, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension; Anti-Infective Agents; Anti-Bacterial Agents; Minocycline
• Other Study ID Numbers: DHC20180023

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No