<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/NCT03040128</url>
  </required_header>
  <id_info>
    <org_study_id>MITCH</org_study_id>
    <nct_id>NCT03040128</nct_id>
  </id_info>
  <brief_title>Use of Minocycline in Intracerebral Hemorrhage</brief_title>
  <official_title>Minocycline and Matrix Metalloproteinase Inhibition in Acute Intracerebral Hemorrhage: A Pilot Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Tennessee</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of Southern California</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Tennessee</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      To date, no neuroprotective drugs have demonstrated clinical efficacy in intracerebral&#xD;
      hemorrhage (ICH). This study will use intravenous (IV) minocycline in ICH to evaluate for (1)&#xD;
      safety/ tolerability and (2) evaluate for clinical efficacy&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Intracerebral hemorrhage (ICH) remains a devastating neurological disorder with high&#xD;
      mortality and poor prognosis with unchanged mortality rates (53-59%). Acute treatment options&#xD;
      for ICH remain supportive with no available effective drug or surgical therapy. All trials so&#xD;
      far have failed to improve clinical outcome in randomized, double-blinded trials. However,&#xD;
      one area of interest has been maintaining the integrity of the blood-brain-barrier (BBB) and&#xD;
      preventing the growth of vasogenic edema. Matrix metalloproteinases (MMP) are a family of&#xD;
      ubiquitous zinc-dependent endopeptidase enzymes whose primary function is the digestion of&#xD;
      collagen type IV, laminin, and fibronectin for the purpose of remodeling extracellular basal&#xD;
      lamina. Elevated MMP-9 as a pathological process associated with larger hematoma volume,&#xD;
      larger perihematomal edema, and poorer clinical outcome in intracerebral hemorrhage is well&#xD;
      documented in animal models and patients. One particular MMP-9 inhibitor gaining usage in&#xD;
      cerebrovascular disease is minocycline. Normally FDA-approved for bacterial infection and&#xD;
      acne vulgaris, minocycline has also been found to be both a safe and effective treatment in&#xD;
      ischemic stroke; its potential role as a neuroprotectant in ischemic stroke is currently&#xD;
      being tested in a large, randomized, double-blinded trial. Minocycline's beneficial role as a&#xD;
      neuroprotectant may also extend to ICH. By inhibiting MMP-9, minocycline may decrease BBB&#xD;
      permeability, resulting in less perihematomal edema and decreased mass effect. Although&#xD;
      numerous animal ICH models support minocycline's role as an inhibitor of MMP-9 and&#xD;
      neuroprotectant, its use has never been studied in humans with ICH.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 27, 2013</start_date>
  <completion_date type="Actual">November 30, 2016</completion_date>
  <primary_completion_date type="Actual">November 30, 2016</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <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>
    <masking_description>random number generator (placebo vs. study drug)</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Number of patients with Treatment-related Adverse Effects</measure>
    <time_frame>day 90</time_frame>
    <description>Treatment-related adverse effects as noted by package insert: fever, nausea, vomiting, C-diff, hepatic toxicity, dermatitis, anaphylaxis, renal injury)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Volume (ml) of Perihematomal Edema</measure>
    <time_frame>Change from baseline perihematomal edema volume to chronic (day 5-11) perihematomal edema volume</time_frame>
    <description>Volumetric analysis (ml) computed from computed tomography head</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>modified Rankin score</measure>
    <time_frame>day 90</time_frame>
    <description>modified Rankin score (points ranging from 0 to 6)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Barthel Index</measure>
    <time_frame>day 90</time_frame>
    <description>Barthel Index score (points ranging from 0 to 100)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>National Institutes of Health Stroke Scale Score</measure>
    <time_frame>day 90</time_frame>
    <description>National Institutes of Health Stroke Scale Score (points ranging from 0 to 42)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Glasgow Coma Score</measure>
    <time_frame>day 90</time_frame>
    <description>Glasgow Coma Score (points ranging from 3 to 15)</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">20</enrollment>
  <condition>Intracerebral Hemorrhage</condition>
  <arm_group>
    <arm_group_label>placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>normal saline infusion</description>
  </arm_group>
  <arm_group>
    <arm_group_label>minocycline</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>intravenous minocycline</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Minocycline</intervention_name>
    <description>high-dose, intravenous minocycline</description>
    <arm_group_label>minocycline</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>normal saline infusion</intervention_name>
    <arm_group_label>placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria:&#xD;
&#xD;
          1. Age 18-80 yo&#xD;
&#xD;
          2. Acute neurological deficit with corresponding ICH noted on head CT&#xD;
&#xD;
          3. Glasgow Coma Scale (GCS) &gt; 8&#xD;
&#xD;
          4. Onset of symptoms within 12 hrs&#xD;
&#xD;
          5. &lt; 30 ml of blood noted on initial CTH (30 ml hematoma volume is a noted independent&#xD;
             marker between good and poor clinical outcome)&#xD;
&#xD;
          6. ICH score &lt; 3&#xD;
&#xD;
          7. English/ Spanish speaking&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Allergy to tetracycline and tetracycline analogues&#xD;
&#xD;
          2. Pregnancy or suspected pregnancy&#xD;
&#xD;
          3. Hepatic and/or renal insufficiency (LFTs 3x greater than upper limit of normal;&#xD;
             creatinine &gt; 2 mg/dL)&#xD;
&#xD;
          4. Thrombocytopenia (plt count &lt; 75,000)&#xD;
&#xD;
          5. History of intolerance to minocycline&#xD;
&#xD;
          6. Baseline modified Rankin score &gt; 1&#xD;
&#xD;
          7. Stuporous or comatose (GCS &lt; 8)&#xD;
&#xD;
          8. Presence of concomitant serious illness that would confound study, including serious&#xD;
             psychiatric disease or prior suicide attempts.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <verification_date>January 2017</verification_date>
  <study_first_submitted>January 25, 2017</study_first_submitted>
  <study_first_submitted_qc>January 30, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">February 2, 2017</study_first_posted>
  <last_update_submitted>January 30, 2017</last_update_submitted>
  <last_update_submitted_qc>January 30, 2017</last_update_submitted_qc>
  <last_update_posted type="Estimate">February 2, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Tennessee</investigator_affiliation>
    <investigator_full_name>Jason Chang</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cerebral Hemorrhage</mesh_term>
    <mesh_term>Hemorrhage</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>
  <pending_results>
    <submitted>May 3, 2018</submitted>
    <returned>June 4, 2018</returned>
  </pending_results>
  <!-- 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/NCT03040128
org study id: MITCH
nct id: NCT03040128
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
To date, no neuroprotective drugs have demonstrated clinical efficacy in intracerebral
      hemorrhage (ICH). This study will use intravenous (IV) minocycline in ICH to evaluate for (1)
      safety/ tolerability and (2) evaluate for clinical efficacy
Intracerebral hemorrhage (ICH) remains a devastating neurological disorder with high
      mortality and poor prognosis with unchanged mortality rates (53-59%). Acute treatment options
      for ICH remain supportive with no available effective drug or surgical therapy. All trials so
      far have failed to improve clinical outcome in randomized, double-blinded trials. However,
      one area of interest has been maintaining the integrity of the blood-brain-barrier (BBB) and
      preventing the growth of vasogenic edema. Matrix metalloproteinases (MMP) are a family of
      ubiquitous zinc-dependent endopeptidase enzymes whose primary function is the digestion of
      collagen type IV, laminin, and fibronectin for the purpose of remodeling extracellular basal
      lamina. Elevated MMP-9 as a pathological process associated with larger hematoma volume,
      larger perihematomal edema, and poorer clinical outcome in intracerebral hemorrhage is well
      documented in animal models and patients. One particular MMP-9 inhibitor gaining usage in
      cerebrovascular disease is minocycline. Normally FDA-approved for bacterial infection and
      acne vulgaris, minocycline has also been found to be both a safe and effective treatment in
      ischemic stroke; its potential role as a neuroprotectant in ischemic stroke is currently
      being tested in a large, randomized, double-blinded trial. Minocycline's beneficial role as a
      neuroprotectant may also extend to ICH. By inhibiting MMP-9, minocycline may decrease BBB
      permeability, resulting in less perihematomal edema and decreased mass effect. Although
      numerous animal ICH models support minocycline's role as an inhibitor of MMP-9 and
      neuroprotectant, its use has never been studied in humans with ICH.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: random number generator (placebo vs. study drug)
measure: Number of patients with Treatment-related Adverse Effects
time frame: day 90
description: Treatment-related adverse effects as noted by package insert: fever, nausea, vomiting, C-diff, hepatic toxicity, dermatitis, anaphylaxis, renal injury)
measure: Volume (ml) of Perihematomal Edema
time frame: Change from baseline perihematomal edema volume to chronic (day 5-11) perihematomal edema volume
description: Volumetric analysis (ml) computed from computed tomography head
measure: modified Rankin score
time frame: day 90
description: modified Rankin score (points ranging from 0 to 6)
measure: Barthel Index
time frame: day 90
description: Barthel Index score (points ranging from 0 to 100)
measure: National Institutes of Health Stroke Scale Score
time frame: day 90
description: National Institutes of Health Stroke Scale Score (points ranging from 0 to 42)
measure: Glasgow Coma Score
time frame: day 90
description: Glasgow Coma Score (points ranging from 3 to 15)
arm group label: placebo
arm group type: Placebo Comparator
description: normal saline infusion
arm group label: minocycline
arm group type: Experimental
description: intravenous minocycline
intervention type: Drug
intervention name: Minocycline
description: high-dose, intravenous minocycline
arm group label: minocycline
intervention type: Other
intervention name: normal saline infusion
arm group label: placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: Accepts Healthy Volunteers
responsible party type: Principal Investigator
investigator affiliation: University of Tennessee
investigator full name: Jason Chang
investigator title: Principal Investigator
mesh term: Cerebral Hemorrhage
mesh term: Hemorrhage
mesh term: Minocycline
sharing ipd: No
submitted: May 3, 2018
returned: June 4, 2018