Hydroxychloroquine and Cognitive Function After Surgery

Duke University

Status and phase: Terminated; Phase 4

Conditions: Individuals Undergoing Cardiac and General Surgery

Treatments: Drug: Hydroxychloroquine

Study type: Interventional

Funder types: Other

Identifiers

NCT03025087

Pro00046611

Details and patient eligibility

About

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

Full 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.

Enrollment: 24 patients

Sex: All

Ages: 50+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Male or female, age ≥ 50 years old.
2. Patients scheduled to undergo cardiac surgery (CABG, CABG + Valve, Valve) with CPB.
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 a 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 < 30ml/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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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24 participants in 5 patient groups

Phase 1

Experimental group

Description:

6 evaluable subjects (3 cardiac, 3 noncardiac patients): 1000 mg HCQ on the day prior to surgery.

Treatment:

Drug: Hydroxychloroquine

Phase 2

Experimental group

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

Treatment:

Drug: Hydroxychloroquine

Phase 3

Experimental group

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.

Treatment:

Drug: Hydroxychloroquine

Phase 4

Experimental group

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.

Treatment:

Drug: Hydroxychloroquine

Phase 5

Experimental group

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.

Treatment:

Drug: Hydroxychloroquine