Hydroxychloroquine and Cognitive Function After Surgery

Phase 4

Terminated

Conditions: Individuals Undergoing Cardiac and General Surgery

Interventions: Drug: Hydroxychloroquine

Registration Number: NCT03025087

Lead Sponsor: Duke University

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

Detailed Description: 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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 24

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Phase 1	Hydroxychloroquine	6 evaluable subjects (3 cardiac, 3 noncardiac patients): 1000 mg HCQ on the day prior to surgery.
Phase 2	Hydroxychloroquine	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
Phase 4	Hydroxychloroquine	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.
Phase 3	Hydroxychloroquine	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.
Phase 5	Hydroxychloroquine	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.

Primary Outcome Measures

Name	Time	Method
Ktrans Volume Transfer Constant	Postoperative day 1-5	Ktrans represents the "permeability" or "leakage" constant across the blood-brain barrier and is calculated by measuring the amount of gadolinium-based contrast agent in the extravascular-extracellular space. Ktrans is a constant assessed on the postoperative MRI and has no units of measure.

Secondary Outcome Measures