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Hydroxychloroquine and Cognitive Function After Surgery

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ClinicalTrials.gov Identifier: NCT03025087
Recruitment Status : Suspended (Recruitment suspending during the COVID-19 pandemic.)
First Posted : January 19, 2017
Last Update Posted : April 21, 2020
Sponsor:
Information provided by (Responsible Party):
Duke University

Brief Summary:
The purpose of this study is to determine whether hydroxychloroquine decreases the relative leakage of the brain barrier after surgery.

Condition or disease Intervention/treatment Phase
Individuals Undergoing Cardiac and General Surgery Drug: Hydroxychloroquine Phase 4

Detailed Description:
Hydroxychloroquine will be administered preoperatively to 30 patients undergoing cardiac or noncardiac 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Hydroxychloroquine and Cognitive Function After Surgery
Actual Study Start Date : June 19, 2017
Estimated Primary Completion Date : March 2021
Estimated Study Completion Date : March 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Phase 1
6 evaluable subjects (3 cardiac, 3 noncardiac patients): 1000 mg HCQ on the day prior to surgery.
Drug: Hydroxychloroquine
Participants will be getting hydroxychloroquine

Experimental: Phase 2
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
Drug: Hydroxychloroquine
Participants will be getting hydroxychloroquine

Experimental: Phase 3
6 evaluable subjects (3 cardiac, 3 noncardiac patients): 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.
Drug: Hydroxychloroquine
Participants will be getting hydroxychloroquine

Experimental: Phase 4
6 evaluable subjects (3 cardiac, 3 noncardiac patients): 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.
Drug: Hydroxychloroquine
Participants will be getting hydroxychloroquine

Experimental: Phase 5
6 evaluable subjects (3 cardiac, 3 noncardiac patients): 1000 mg HCQ 1-2 hours after separation from CPB or at end of noncardiac surgery 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.
Drug: Hydroxychloroquine
Participants will be getting hydroxychloroquine




Primary Outcome Measures :
  1. Ratio of T1 relaxivity difference [ Time Frame: Postoperative day 1-5 ]
    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.



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Ages Eligible for Study:   50 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female, age ≥ 50 years old.
  2. Patients scheduled to undergo cardiac surgery (CABG, CABG + Valve, Valve) with CPB or general surgery (e.g. orthopedic, abdominal, urological).
  3. Patient has voluntarily signed and dated the study-specific informed consent form approved by Duke University Health System Institutional Review Board (DUHS IRB)

Exclusion Criteria:

  1. Cardiac surgery scheduled to be performed without cardiopulmonary bypass
  2. Patients requiring emergent operation
  3. Patients with a history of myocardial infarction within 7 days of surgery
  4. Patients with a history of porphyria, psoriasis, chronic dermatitis, or retinal disease
  5. Patients receiving preoperative digoxin
  6. Patients with symptomatic cerebrovascular disease with substantial residual deficit
  7. Patients with a history of alcohol abuse within 2 years of screening
  8. Patients with history of psychiatric illness and/or anxiety requiring medical treatment.
  9. Patients with impaired liver and/or kidney functions (AST, ALT 2 times the upper limit of normal)
  10. Patients with impaired renal functions (GFR < 60ml/min)
  11. Patients with less than a 7th grade education or unable to read and thus unable complete the neuropsychological testing
  12. Patients scoring < 26 on a baseline Mini Mental State examination (MMSE) or scoring >27 on the Center for Epidemiological Studies - Depression (CES-D) scale
  13. Female subjects of childbearing potential who have had menstrual period within the past two years
  14. Patients with bodily implants unsafe for MRI use
  15. Patients with a history of claustrophobia
  16. Known or suspected hypersensitivity to quinine (chloroquine or hydroxychloroquine)
  17. Patient with pre-existing diagnosis of G6PD deficiency
  18. Patients who have participated in another interventional clinical study within the previous 30 days
  19. Any other concurrent disease or illness that, in the opinion of the investigator, makes the patient unsuitable for the study
  20. Major ophthalmologic comorbidities (ex: ruptured globe, retinal vascular occlusive disease, retinal artery occlusion, anterior ischemic optic neuropathy, media opacification due to corneal abnormalities or cataract that prevent ocular and optical coherence tomography examination, glaucoma, age-related macular degeneration, history of intravitreal injections, and macular edema)
  21. Patients who have received chemotherapy in the last 12 months
  22. Patient with a QTc of 450 msec or greater (or 500 msec or greater in those with known IVCD, RBBB, or LBBB) at baseline will be excluded.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03025087


Locations
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United States, North Carolina
Duke Health
Durham, North Carolina, United States, 27710
Sponsors and Collaborators
Duke University
Investigators
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Principal Investigator: Joseph P Mathew, MD Duke Health
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Responsible Party: Duke University
ClinicalTrials.gov Identifier: NCT03025087    
Other Study ID Numbers: Pro00046611
First Posted: January 19, 2017    Key Record Dates
Last Update Posted: April 21, 2020
Last Verified: April 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Hydroxychloroquine
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antirheumatic Agents