Hydroxychloroquine and Cognitive Function After Surgery

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

Detailed Description
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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.

Official Title
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Hydroxychloroquine and Cognitive Function After Surgery

Conditions
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Individuals Undergoing Cardiac and General Surgery

Intervention / Treatment
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* Drug: Hydroxychloroquine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, age ≥ 50 years old. Patients scheduled to undergo cardiac surgery (CABG, CABG + Valve, Valve) with CPB. 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: Cardiac surgery scheduled to be performed without cardiopulmonary bypass Patients requiring emergent operation Patients with a history of myocardial infarction within 7 days of surgery Patients with a history of porphyria, psoriasis, chronic dermatitis, or retinal disease Patients receiving preoperative digoxin Patients with symptomatic cerebrovascular disease with substantial residual deficit Patients with a history of alcohol abuse within 2 years of screening Patients with a history of psychiatric illness and/or anxiety requiring medical treatment. Patients with impaired liver and/or kidney functions (AST, ALT 2 times the upper limit of normal) Patients with impaired renal functions (GFR < 30ml/min) Patients with less than a 7th-grade education or unable to read and thus unable complete the neuropsychological testing Patients scoring < 26 on a baseline Mini Mental State examination (MMSE) or scoring >27 on the Center for Epidemiological Studies - Depression (CES-D) scale Female subjects of childbearing potential who have had menstrual period within the past two years Patients with bodily implants unsafe for MRI use Patients with a history of claustrophobia Known or suspected hypersensitivity to quinine (chloroquine or hydroxychloroquine) Patient with pre-existing diagnosis of G6PD deficiency Patients who have participated in another interventional clinical study within the previous 30 days Any other concurrent disease or illness that, in the opinion of the investigator, makes the patient unsuitable for the study 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) Patients who have received chemotherapy in the last 12 months 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.

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase 1<br>6 evaluable subjects (3 cardiac, 3 noncardiac patients): 1000 mg HCQ on the day prior to surgery. | Drug: Hydroxychloroquine<br>* Participants will be getting hydroxychloroquine<br>|
| Experimental: Phase 2<br>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<br>* Participants will be getting hydroxychloroquine<br>|
| Experimental: Phase 3<br>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. | Drug: Hydroxychloroquine<br>* Participants will be getting hydroxychloroquine<br>|
| Experimental: Phase 4<br>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. | Drug: Hydroxychloroquine<br>* Participants will be getting hydroxychloroquine<br>|
| Experimental: Phase 5<br>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. | Drug: Hydroxychloroquine<br>* Participants will be getting hydroxychloroquine<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ratio of T1 relaxivity difference | 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. | Postoperative day 1-5 |