<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04478500</url>
  </required_header>
  <id_info>
    <org_study_id>DHC20180023</org_study_id>
    <nct_id>NCT04478500</nct_id>
  </id_info>
  <brief_title>Neuroinflammation in Hypertension Study</brief_title>
  <acronym>MINIHT</acronym>
  <official_title>The Role of Neuroinflammation in Hypertension.Minocycline for Resistant Hypertension: a Randomized Double Blind Placebo-Controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Royal Perth Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Royal Perth Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      To demonstrate that in patients with resistant hypertension oral treatment with minocycline&#xD;
      via inhibition of central immune cell activation and inflammation results in reduced central&#xD;
      sympathetic outflow and concomitant lowering of BP.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a randomized, double-blind, placebo controlled, parallel group design study aiming to&#xD;
      compare the effects of minocycline 100mg twice daily vs matched placebo for 12 weeks on&#xD;
      ambulatory BP and the parameters of sympathetic and immune activation&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">July 2, 2020</start_date>
  <completion_date type="Anticipated">February 1, 2025</completion_date>
  <primary_completion_date type="Anticipated">August 1, 2024</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The difference in the daytime systolic blood pressure between groups after respective treatment.</measure>
    <time_frame>12 weeks</time_frame>
    <description>Office and ambulatory blood pressures</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Assessment of change in central and peripheral inflammation</measure>
    <time_frame>12 weeks</time_frame>
    <description>FDG PET</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in muscle sympathetic nerve activity</measure>
    <time_frame>12 weeks</time_frame>
    <description>Muscle sympathetic nerve activity assessed by microneurography</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in central Blood Pressure</measure>
    <time_frame>12 weeks</time_frame>
    <description>central Blood Pressure assessed by Sphygmocor XCEL</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">60</enrollment>
  <condition>Resistant Hypertension</condition>
  <arm_group>
    <arm_group_label>Minocycline Group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Subjects will be randomized to receive Minocycline 100mg twice daily</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo Group</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Subjects will be randomized to receive placebo.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Minocycline</intervention_name>
    <description>Participants will be randomly assigned to receive either Minocycline 100mg twice daily or Placebo.&#xD;
Comprehensive testing will be performed at baseline, and at the end of the 12 week intervention phase.</description>
    <arm_group_label>Minocycline Group</arm_group_label>
    <arm_group_label>Placebo Group</arm_group_label>
    <other_name>Akamin</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Aged: 45 -65 years&#xD;
&#xD;
          -  Signed informed consent&#xD;
&#xD;
          -  Clinical diagnosis of Resistant Hypertension&#xD;
&#xD;
          -  Daytime systolic ambulatory BP &gt;135mmHg.&#xD;
&#xD;
        Exclusion Criteria:• eGFR of &lt;45 mL/min/1.73m2&#xD;
&#xD;
          -  History of myocardial infarction (MI) or any cardiovascular event within 3 months of&#xD;
             screening period, clinically significant AV conduction disturbances and/or&#xD;
             arrhythmias,&#xD;
&#xD;
          -  current of past history of heart failure (LVEF ≤40%)&#xD;
&#xD;
          -  psychotropic agents, antidepressants and NSAIDS&#xD;
&#xD;
          -  alcohol consumption of &gt;3 standard drinks.&#xD;
&#xD;
          -  known hypersensitivity or contraindication to minocycline or other tetracyclines.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>45 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Markus Schlaich, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Western Australia and Royal Perth Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Revathy Carnagarin, MD</last_name>
    <phone>+61892240316</phone>
    <email>revathy.carnagarin@uwa.edu.au</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Omar Azzam, MD</last_name>
    <phone>+61892242244</phone>
    <email>omar.azzam@health.wa.gov.au</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Royal Perth Hospital</name>
      <address>
        <city>Perth</city>
        <state>Western Australia</state>
        <zip>6000</zip>
        <country>Australia</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Anu Joyson, MSC RN</last_name>
      <phone>=08 922</phone>
      <phone_ext>40390</phone_ext>
      <email>anu.joyson@uwa.edu.au</email>
    </contact>
    <investigator>
      <last_name>Markus Schlaich, Prof</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Australia</country>
  </location_countries>
  <reference>
    <citation>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.</citation>
    <PMID>30129037</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>25963715</PMID>
  </reference>
  <verification_date>September 2022</verification_date>
  <study_first_submitted>July 10, 2020</study_first_submitted>
  <study_first_submitted_qc>July 16, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 20, 2020</study_first_posted>
  <last_update_submitted>September 28, 2022</last_update_submitted>
  <last_update_submitted_qc>September 28, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">September 29, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Royal Perth Hospital</investigator_affiliation>
    <investigator_full_name>Dr Markus Schlaich</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neuroinflammatory Diseases</mesh_term>
    <mesh_term>Hypertension</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Minocycline</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04478500
org study id: DHC20180023
nct id: NCT04478500
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
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.
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
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: The difference in the daytime systolic blood pressure between groups after respective treatment.
time frame: 12 weeks
description: Office and ambulatory blood pressures
measure: Assessment of change in central and peripheral inflammation
time frame: 12 weeks
description: FDG PET
measure: Change in muscle sympathetic nerve activity
time frame: 12 weeks
description: Muscle sympathetic nerve activity assessed by microneurography
measure: Change in central Blood Pressure
time frame: 12 weeks
description: central Blood Pressure assessed by Sphygmocor XCEL
arm group label: Minocycline Group
arm group type: Active Comparator
description: Subjects will be randomized to receive Minocycline 100mg twice daily
arm group label: Placebo Group
arm group type: Placebo Comparator
description: Subjects will be randomized to receive placebo.
intervention type: Drug
intervention name: Minocycline
description: 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.
arm group label: Minocycline Group
arm group label: Placebo Group
other name: Akamin
criteria: 
gender: All
minimum age: 45 Years
maximum age: 65 Years
healthy volunteers: No
last name: Markus Schlaich, MD
role: Principal Investigator
affiliation: University of Western Australia and Royal Perth Hospital
last name: Revathy Carnagarin, MD
phone: +61892240316
email: revathy.carnagarin@uwa.edu.au
last name: Omar Azzam, MD
phone: +61892242244
email: omar.azzam@health.wa.gov.au
facility: 
status: Recruiting
contact: 
investigator: 
country: Australia
citation: 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.
PMID: 30129037
citation: 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.
PMID: 25963715
responsible party type: Principal Investigator
investigator affiliation: Royal Perth Hospital
investigator full name: Dr Markus Schlaich
investigator title: Professor
mesh term: Neuroinflammatory Diseases
mesh term: Hypertension
mesh term: Minocycline
sharing ipd: No