<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/NCT03025087</url>
  </required_header>
  <id_info>
    <org_study_id>Pro00046611</org_study_id>
    <nct_id>NCT03025087</nct_id>
  </id_info>
  <brief_title>Hydroxychloroquine and Cognitive Function After Surgery</brief_title>
  <official_title>Hydroxychloroquine and Cognitive Function After Surgery</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Duke University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Duke University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to determine whether hydroxychloroquine decreases the relative&#xD;
      leakage of the brain barrier after surgery.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Hydroxychloroquine will be administered preoperatively to 30 patients undergoing cardiac&#xD;
      surgery. All patients will undergo magnetic resonance imaging (MRI) with gadolinium in the&#xD;
      post-operative period before hospital discharge in order to assess blood-brain barrier&#xD;
      permeability.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Suspended</overall_status>
  <why_stopped>
    Interim analysis&#xD;
  </why_stopped>
  <start_date type="Actual">June 19, 2017</start_date>
  <completion_date type="Anticipated">December 2024</completion_date>
  <primary_completion_date type="Anticipated">December 2024</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Ratio of T1 relaxivity difference</measure>
    <time_frame>Postoperative day 1-5</time_frame>
    <description>Relative blood brain barrier leakage for the segmented regions of interest (cortex, diencephalon, hippocampus, cerebellum, global) will be expressed as the ratio of T1 relaxivity difference between the initial and final post-contrast maps divided by magnitude of the initial enhancement from baseline. All positive ratios represent a relative magnitude estimate of contrast retention in brain extracellular space.</description>
  </primary_outcome>
  <number_of_arms>5</number_of_arms>
  <enrollment type="Anticipated">30</enrollment>
  <condition>Individuals Undergoing Cardiac and General Surgery</condition>
  <arm_group>
    <arm_group_label>Phase 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>6 evaluable subjects (3 cardiac, 3 noncardiac patients): 1000 mg HCQ on the day prior to surgery.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Phase 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>6 evaluable subjects (3 cardiac, 3 noncardiac patients): 1000 mg HCQ on the day prior to surgery followed by 400 mg daily until the day of MRI imaging on postoperative day 1-5</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Phase 3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>6 evaluable cardiac subjects 1000 mg HCQ on the day prior to surgery followed by 400 mg twice daily (800 mg total) until the day of MRI imaging on postoperative day 1-5.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Phase 4</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>6 evaluable cardiac subjects: 1000 mg HCQ on the day prior to surgery followed by 500 mg twice daily (1000 mg total) until the day of MRI imaging on postoperative day 1-5.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Phase 5</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>6 evaluable cardiac subjects: 1000 mg HCQ 1-2 hours after separation from CPB followed by the highest tolerated dose from the previous 4 phases divided into 2 equal daily doses until the day of MRI imaging on postoperative day 1-5.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Hydroxychloroquine</intervention_name>
    <description>Participants will be getting hydroxychloroquine</description>
    <arm_group_label>Phase 1</arm_group_label>
    <arm_group_label>Phase 2</arm_group_label>
    <arm_group_label>Phase 3</arm_group_label>
    <arm_group_label>Phase 4</arm_group_label>
    <arm_group_label>Phase 5</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male or female, age ≥ 50 years old.&#xD;
&#xD;
          2. Patients scheduled to undergo cardiac surgery (CABG, CABG + Valve, Valve) with CPB.&#xD;
&#xD;
          3. Patient has voluntarily signed and dated the study-specific informed consent form&#xD;
             approved by Duke University Health System Institutional Review Board (DUHS IRB)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Cardiac surgery scheduled to be performed without cardiopulmonary bypass&#xD;
&#xD;
          2. Patients requiring emergent operation&#xD;
&#xD;
          3. Patients with a history of myocardial infarction within 7 days of surgery&#xD;
&#xD;
          4. Patients with a history of porphyria, psoriasis, chronic dermatitis, or retinal&#xD;
             disease&#xD;
&#xD;
          5. Patients receiving preoperative digoxin&#xD;
&#xD;
          6. Patients with symptomatic cerebrovascular disease with substantial residual deficit&#xD;
&#xD;
          7. Patients with a history of alcohol abuse within 2 years of screening&#xD;
&#xD;
          8. Patients with a history of psychiatric illness and/or anxiety requiring medical&#xD;
             treatment.&#xD;
&#xD;
          9. Patients with impaired liver and/or kidney functions (AST, ALT 2 times the upper limit&#xD;
             of normal)&#xD;
&#xD;
         10. Patients with impaired renal functions (GFR &lt; 30ml/min)&#xD;
&#xD;
         11. Patients with less than a 7th-grade education or unable to read and thus unable&#xD;
             complete the neuropsychological testing&#xD;
&#xD;
         12. Patients scoring &lt; 26 on a baseline Mini Mental State examination (MMSE) or scoring&#xD;
             &gt;27 on the Center for Epidemiological Studies - Depression (CES-D) scale&#xD;
&#xD;
         13. Female subjects of childbearing potential who have had menstrual period within the&#xD;
             past two years&#xD;
&#xD;
         14. Patients with bodily implants unsafe for MRI use&#xD;
&#xD;
         15. Patients with a history of claustrophobia&#xD;
&#xD;
         16. Known or suspected hypersensitivity to quinine (chloroquine or hydroxychloroquine)&#xD;
&#xD;
         17. Patient with pre-existing diagnosis of G6PD deficiency&#xD;
&#xD;
         18. Patients who have participated in another interventional clinical study within the&#xD;
             previous 30 days&#xD;
&#xD;
         19. Any other concurrent disease or illness that, in the opinion of the investigator,&#xD;
             makes the patient unsuitable for the study&#xD;
&#xD;
         20. Major ophthalmologic comorbidities (ex: ruptured globe, retinal vascular occlusive&#xD;
             disease, retinal artery occlusion, anterior ischemic optic neuropathy, media&#xD;
             opacification due to corneal abnormalities or cataract that prevent ocular and optical&#xD;
             coherence tomography examination, glaucoma, age-related macular degeneration, history&#xD;
             of intravitreal injections, and macular edema)&#xD;
&#xD;
         21. Patients who have received chemotherapy in the last 12 months&#xD;
&#xD;
         22. Patient with a QTc of 450 msec or greater (or 500 msec or greater in those with known&#xD;
             IVCD, RBBB, or LBBB) at baseline will be excluded.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>50 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Joseph P Mathew, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Duke Health</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Duke Health</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27710</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>January 17, 2017</study_first_submitted>
  <study_first_submitted_qc>January 17, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 19, 2017</study_first_posted>
  <last_update_submitted>August 18, 2023</last_update_submitted>
  <last_update_submitted_qc>August 18, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 22, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hydroxychloroquine</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/NCT03025087
org study id: Pro00046611
nct id: NCT03025087
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
The purpose of this study is to determine whether hydroxychloroquine decreases the relative
      leakage of the brain barrier after surgery.
Hydroxychloroquine will be administered preoperatively to 30 patients undergoing cardiac
      surgery. All patients will undergo magnetic resonance imaging (MRI) with gadolinium in the
      post-operative period before hospital discharge in order to assess blood-brain barrier
      permeability.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Ratio of T1 relaxivity difference
time frame: Postoperative day 1-5
description: Relative blood brain barrier leakage for the segmented regions of interest (cortex, diencephalon, hippocampus, cerebellum, global) will be expressed as the ratio of T1 relaxivity difference between the initial and final post-contrast maps divided by magnitude of the initial enhancement from baseline. All positive ratios represent a relative magnitude estimate of contrast retention in brain extracellular space.
arm group label: Phase 1
arm group type: Experimental
description: 6 evaluable subjects (3 cardiac, 3 noncardiac patients): 1000 mg HCQ on the day prior to surgery.
arm group label: Phase 2
arm group type: Experimental
description: 6 evaluable subjects (3 cardiac, 3 noncardiac patients): 1000 mg HCQ on the day prior to surgery followed by 400 mg daily until the day of MRI imaging on postoperative day 1-5
arm group label: Phase 3
arm group type: Experimental
description: 6 evaluable cardiac subjects 1000 mg HCQ on the day prior to surgery followed by 400 mg twice daily (800 mg total) until the day of MRI imaging on postoperative day 1-5.
arm group label: Phase 4
arm group type: Experimental
description: 6 evaluable cardiac subjects: 1000 mg HCQ on the day prior to surgery followed by 500 mg twice daily (1000 mg total) until the day of MRI imaging on postoperative day 1-5.
arm group label: Phase 5
arm group type: Experimental
description: 6 evaluable cardiac subjects: 1000 mg HCQ 1-2 hours after separation from CPB followed by the highest tolerated dose from the previous 4 phases divided into 2 equal daily doses until the day of MRI imaging on postoperative day 1-5.
intervention type: Drug
intervention name: Hydroxychloroquine
description: Participants will be getting hydroxychloroquine
arm group label: Phase 1
arm group label: Phase 2
arm group label: Phase 3
arm group label: Phase 4
arm group label: Phase 5
criteria: 
gender: All
minimum age: 50 Years
maximum age: N/A
healthy volunteers: No
last name: Joseph P Mathew, MD
role: Principal Investigator
affiliation: Duke Health
facility: 
country: United States
responsible party type: Sponsor
mesh term: Hydroxychloroquine
sharing ipd: No