<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/NCT03814850</url>
  </required_header>
  <id_info>
    <org_study_id>20191282</org_study_id>
    <secondary_id>20180869</secondary_id>
    <nct_id>NCT03814850</nct_id>
  </id_info>
  <brief_title>Remote Ischemic PreConditioning (RIPC)</brief_title>
  <official_title>Remote Ischemic PreConditioning Provides Neuroprotection: A Phase 2, Single Center, Randomized, Double-Blind, Sham-Controlled, Safety and Efficacy Study Evaluating the Use of Remote Ischemic Preconditioning in Patients Undergoing Endovascular Repair of Brain Aneurysms</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sebastian Koch</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Miami</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to learn about protecting the brain from low blood flow&#xD;
      (ischemia) with limb preconditioning. From human studies the investigators know that the&#xD;
      brain can be protected from dangerous low blood flow by reducing the blood flow to an arm or&#xD;
      leg for just a short period of time. This is called limb preconditioning. The investigators&#xD;
      are studying the safety and feasibility of preconditioning and their effect of protecting the&#xD;
      brain from ischemia in two different groups. This is a Phase 2, randomized, double-blind,&#xD;
      sham-controlled, design. Up to 50 male and female patients undergoing elective endovascular&#xD;
      repair of unruptured brain aneurysm who are randomized to the remote ischemic preconditioned&#xD;
      or sham group will be enrolled. This study consists of one 3-9 month study period for each&#xD;
      patient plus up to 14 days for enrollment activities. Subjects are required to return between&#xD;
      3-9 months for end-of-study procedures.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Not yet recruiting</overall_status>
  <start_date type="Anticipated">December 1, 2023</start_date>
  <completion_date type="Anticipated">December 31, 2025</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2025</primary_completion_date>
  <phase>N/A</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>Supportive Care</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>The person performing the RIPC is not blinded.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence of all adverse events and serious adverse events.</measure>
    <time_frame>9 months</time_frame>
    <description>Adverse events are all conditions/symptoms/findings and all abnormal clinically significant laboratory tests both expected and unexpected, occurring from onset of the intervention until study completion.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in procedurally-induced vascular cognitive impairment.</measure>
    <time_frame>Baseline, Day 2-4</time_frame>
    <description>As measured by the NIH-toolbox for neurocognitive testing.NIH-Toolbox normalized scores to define a single cognitive battery index.C. Score:0= No deficit, no change; 400= Maximum deficit.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in procedurally-induced vascular cognitive impairment.</measure>
    <time_frame>Baseline, 3-9 months.</time_frame>
    <description>As measured by the NIH-toolbox for neurocognitive testing. NIH-Toolbox normalized scores to define a single cognitive battery index.C. Score:0= No deficit, no change; 400= Maximum deficit</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Volume of embolic strokes by Diffusion Weighted Imaging (DWI).</measure>
    <time_frame>Timeframe: Baseline, 12-96 hours post procedures</time_frame>
    <description>Measured in select patients by Diffusion Weighted Imaging (DWI) via Magnetic Resonance Imaging (MRI) that undergo 4 cycles of 5 minutes of limb ischemia followed by 5 minutes reperfusion.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Volume of embolic strokes by Fluid-attenuated Inversion Recovery (FLAIR).</measure>
    <time_frame>Timeframe: Baseline, 12-96 hours post procedures.</time_frame>
    <description>Measured in select patients by Fluid-attenuated Inversion Recovery (FLAIR) via Magnetic Resonance Imaging (MRI) that undergo 4 cycles of 5 minutes of limb ischemia followed by 5 minutes reperfusion.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Frequency of large (&gt;10 cc value) strokes.</measure>
    <time_frame>2-4 days post procedures.</time_frame>
    <description>As measured by MRI imaging when performed.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">50</enrollment>
  <condition>Unruptured Cerebral Aneurysm</condition>
  <arm_group>
    <arm_group_label>Treatment group: standard blood pressure cuff</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>A standard blood pressure cuff inflated on the participants arm for 4 cycles; each cycle will include 5 minutes of inflation followed by 5 minutes of deflection. RIPC will be applied via a standard blood pressure cuff. The ischemic cycle will involve cuff inflating to 30mmHg above resting systolic blood pressure and demonstration of loss of radial pulse.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sham group: standard blood pressure cuff</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
    <description>The blood pressure cuff will be inflated to 30mmHg during the first 5 minutes of each cycle and deflated for the following 5 minutes, with re-demonstration of radial pulse. This will be repeated for 4 cycles.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Standard Manual Aneroid Sphygmomanometer</intervention_name>
    <description>Use of a standard manual blood pressure cuff and manometer for the conditioning intervention.</description>
    <arm_group_label>Sham group: standard blood pressure cuff</arm_group_label>
    <arm_group_label>Treatment group: standard blood pressure cuff</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. A diagnosis of an unruptured brain aneurysm deemed suitable for repair by&#xD;
             neuroendovascular techniques involving intraluminal occlusion by detachable platinum&#xD;
             coils, stent-assisted coiling, pipeline stent, balloon-assisted coiling, covered stent&#xD;
             only, neck-bridge device, re-coiling, or re-treatment of a previously coiled/treated&#xD;
             aneurysm. There are no restrictions on adjunctive devices.&#xD;
&#xD;
          2. Absence of ongoing ischemic symptoms such as transient ischemic attacks, minor&#xD;
             strokes, stroke-in-evolution, or clinical evidence of cerebral vasospasm within 2&#xD;
             weeks prior to randomization. (If a CT scan, cerebral angiogram, or other imaging&#xD;
             performed during the 2 weeks prior to randomization shows radiological vasospasm&#xD;
             deemed by the treating physician to be potentially clinically significant, the subject&#xD;
             is excluded).&#xD;
&#xD;
          3. Male or female with a minimum age of 18 years on the day of enrollment.&#xD;
&#xD;
          4. Informed consent and availability of the subject for the entire study period and&#xD;
             willingness of the subject to adhere to protocol requirements, as evidenced by a&#xD;
             signed Informed Consent Form.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Dissecting or mycotic brain aneurysm. Fusiform or atherosclerotic intracerebral&#xD;
             aneurysms may be eligible for the trial if endovascular treatment is planned with a&#xD;
             goal of exclusion of the aneurysm from the circulation.&#xD;
&#xD;
          2. Planned endovascular vessel sacrifice as the primary modality for aneurysm treatment.&#xD;
&#xD;
          3. Known history of life-threatening allergic reaction to any medication.&#xD;
&#xD;
          4. Soft tissue, orthopedic, or vascular injury which, in the judgment of the&#xD;
             investigator, would preclude arm ischemic conditioning (e.g. superficial wounds,&#xD;
             venous, arterial ulcers, gangrene).&#xD;
&#xD;
          5. History of peripheral vascular disease or deep vein thrombosis in either arm.&#xD;
&#xD;
          6. Women who are pregnant, or have a positive urine or blood (β-hCG) pregnancy test.&#xD;
&#xD;
          7. Women who are breastfeeding.&#xD;
&#xD;
          8. Any clinically significant psychiatric or psychological disease, which would preclude&#xD;
             the patient from completing the protocol.&#xD;
&#xD;
          9. Pre-morbid (estimated) modified Rankin scale score of greater than 2. A subject is not&#xD;
             excluded if they have a pre-morbid modified Rankin scale of greater than 2 but the&#xD;
             disability does not interfere with the subject's ability to complete an MRI and the&#xD;
             cognitive evaluations.&#xD;
&#xD;
         10. Previous serious traumatic brain injury that would preclude the patient from&#xD;
             completing the protocol or preclude MRI analysis of small strokes.&#xD;
&#xD;
         11. Patients with peripherally inserted central catheters, hemodialysis shunts,&#xD;
             arteriovenous fistulae or grafts in the treatment limb, or lymphedema.&#xD;
&#xD;
         12. Patients with known Human Immunodeficiency Virus (HIV) infection.&#xD;
&#xD;
         13. Patients who are unable to have an MRI scan for any reason.&#xD;
&#xD;
         14. Participation in a clinical trial with an investigational drug within 30 days&#xD;
             preceding this study. Previous participation in any clinical trial investigating&#xD;
             ischemia following endovascular aneurysm treatment, participation in another trial&#xD;
             involving RIPC, or prior receipt of RIPC.&#xD;
&#xD;
         15. Severe or unstable concomitant condition disease or chronic condition, which, in the&#xD;
             opinion of the investigator, could affect assessment of the safety or efficacy of&#xD;
             study intervention.&#xD;
&#xD;
         16. Any other medical condition that the site investigator deems would put the patient at&#xD;
             excessive risk of participation in the study or an expected life expectancy less than&#xD;
             1 year or that would result in inability to collect clinical outcomes at 30 days.&#xD;
&#xD;
         17. Systolic blood pressure above 200mm Hg.&#xD;
&#xD;
         18. Cannot tolerate inflation of the tourniquet on their arm consistent with blood&#xD;
             pressure cuff.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Robert Starke, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Miami</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Sebastian Koch, MD</last_name>
    <role>Study Director</role>
    <affiliation>University of Miami</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Robert Starke, M.D.</last_name>
    <phone>305-355-1101</phone>
    <email>RStarke@med.miami.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Sebastian Koch, MD</last_name>
    <phone>305 243-6732</phone>
    <email>skoch@med.miami.edu</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Jackson Memorial Hospital</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33136</zip>
        <country>United States</country>
      </address>
    </facility>
    <contact>
      <last_name>Anabela M Cieslicki</last_name>
      <phone>305-243-8044</phone>
      <email>axc1623@med.miami.edu</email>
    </contact>
    <contact_backup>
      <last_name>Robert Starke, M.D.</last_name>
      <phone>305-355-1101</phone>
      <email>RStarke@med.miami.edu</email>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>University of Miami</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33136</zip>
        <country>United States</country>
      </address>
    </facility>
    <contact>
      <last_name>Anabela M Cieslicki</last_name>
      <phone>305-243-8044</phone>
      <email>axc1623@med.miami.edu</email>
    </contact>
    <contact_backup>
      <last_name>Robert Starke, M.D.</last_name>
      <phone>305-355-1101</phone>
      <email>RStarke@med.miami.edu</email>
    </contact_backup>
    <investigator>
      <last_name>Robert Starke, M.D.</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>January 16, 2019</study_first_submitted>
  <study_first_submitted_qc>January 22, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 24, 2019</study_first_posted>
  <last_update_submitted>April 3, 2023</last_update_submitted>
  <last_update_submitted_qc>April 3, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 4, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>University of Miami</investigator_affiliation>
    <investigator_full_name>Sebastian Koch</investigator_full_name>
    <investigator_title>Professor of Clinical Neurology</investigator_title>
  </responsible_party>
  <keyword>brain aneurysm</keyword>
  <keyword>endovascular repair</keyword>
  <keyword>ischemic stroke</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Intracranial Aneurysm</mesh_term>
    <mesh_term>Aneurysm</mesh_term>
  </condition_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/NCT03814850
org study id: 20191282
secondary id: 20180869
nct id: NCT03814850
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: Yes
The purpose of this study is to learn about protecting the brain from low blood flow
      (ischemia) with limb preconditioning. From human studies the investigators know that the
      brain can be protected from dangerous low blood flow by reducing the blood flow to an arm or
      leg for just a short period of time. This is called limb preconditioning. The investigators
      are studying the safety and feasibility of preconditioning and their effect of protecting the
      brain from ischemia in two different groups. This is a Phase 2, randomized, double-blind,
      sham-controlled, design. Up to 50 male and female patients undergoing elective endovascular
      repair of unruptured brain aneurysm who are randomized to the remote ischemic preconditioned
      or sham group will be enrolled. This study consists of one 3-9 month study period for each
      patient plus up to 14 days for enrollment activities. Subjects are required to return between
      3-9 months for end-of-study procedures.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Supportive Care
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: The person performing the RIPC is not blinded.
measure: Incidence of all adverse events and serious adverse events.
time frame: 9 months
description: Adverse events are all conditions/symptoms/findings and all abnormal clinically significant laboratory tests both expected and unexpected, occurring from onset of the intervention until study completion.
measure: Change in procedurally-induced vascular cognitive impairment.
time frame: Baseline, Day 2-4
description: As measured by the NIH-toolbox for neurocognitive testing.NIH-Toolbox normalized scores to define a single cognitive battery index.C. Score:0= No deficit, no change; 400= Maximum deficit.
measure: Change in procedurally-induced vascular cognitive impairment.
time frame: Baseline, 3-9 months.
description: As measured by the NIH-toolbox for neurocognitive testing. NIH-Toolbox normalized scores to define a single cognitive battery index.C. Score:0= No deficit, no change; 400= Maximum deficit
measure: Volume of embolic strokes by Diffusion Weighted Imaging (DWI).
time frame: Timeframe: Baseline, 12-96 hours post procedures
description: Measured in select patients by Diffusion Weighted Imaging (DWI) via Magnetic Resonance Imaging (MRI) that undergo 4 cycles of 5 minutes of limb ischemia followed by 5 minutes reperfusion.
measure: Volume of embolic strokes by Fluid-attenuated Inversion Recovery (FLAIR).
time frame: Timeframe: Baseline, 12-96 hours post procedures.
description: Measured in select patients by Fluid-attenuated Inversion Recovery (FLAIR) via Magnetic Resonance Imaging (MRI) that undergo 4 cycles of 5 minutes of limb ischemia followed by 5 minutes reperfusion.
measure: Frequency of large (>10 cc value) strokes.
time frame: 2-4 days post procedures.
description: As measured by MRI imaging when performed.
arm group label: Treatment group: standard blood pressure cuff
arm group type: Experimental
description: A standard blood pressure cuff inflated on the participants arm for 4 cycles; each cycle will include 5 minutes of inflation followed by 5 minutes of deflection. RIPC will be applied via a standard blood pressure cuff. The ischemic cycle will involve cuff inflating to 30mmHg above resting systolic blood pressure and demonstration of loss of radial pulse.
arm group label: Sham group: standard blood pressure cuff
arm group type: Sham Comparator
description: The blood pressure cuff will be inflated to 30mmHg during the first 5 minutes of each cycle and deflated for the following 5 minutes, with re-demonstration of radial pulse. This will be repeated for 4 cycles.
intervention type: Device
intervention name: Standard Manual Aneroid Sphygmomanometer
description: Use of a standard manual blood pressure cuff and manometer for the conditioning intervention.
arm group label: Sham group: standard blood pressure cuff
arm group label: Treatment group: standard blood pressure cuff
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Robert Starke, M.D.
role: Principal Investigator
affiliation: University of Miami
last name: Sebastian Koch, MD
role: Study Director
affiliation: University of Miami
last name: Robert Starke, M.D.
phone: 305-355-1101
email: RStarke@med.miami.edu
last name: Sebastian Koch, MD
phone: 305 243-6732
email: skoch@med.miami.edu
facility: 
contact: 
contact backup: 
facility: 
contact: 
contact backup: 
investigator: 
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: University of Miami
investigator full name: Sebastian Koch
investigator title: Professor of Clinical Neurology
mesh term: Intracranial Aneurysm
mesh term: Aneurysm
sharing ipd: No