Hydroxychloroquine and Cognitive Function After Surgery

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

Study Overview

• Status: Active, not recruiting
• Conditions: Individuals Undergoing Cardiac and General Surgery
• Intervention / Treatment: Drug: Hydroxychloroquine

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.

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Bonita Hilliard, RN, BSN; Phone Number: 919-684-0861; Email: bonita.funk@duke.edu
• Study Contact Backup: Name: Joseph P Mathew, MD; Phone Number: 919-681-6646; Email: joseph.mathew@duke.edu

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / 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 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; Participants will be getting hydroxychloroquine
Experimental: Phase 4; 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; Participants will be getting hydroxychloroquine
Experimental: Phase 5; 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; Participants will be getting hydroxychloroquine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ktrans Volume transfer constant	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.	Postoperative day 1-5

Collaborators and Investigators

• Sponsor: Duke University
• Investigators: Principal Investigator: Joseph P Mathew, MD, Duke Health

Study record dates

Study Major Dates

• Study Start (Actual): June 19, 2017
• Primary Completion (Actual): May 22, 2023
• Study Completion (Estimated): June 1, 2024

Study Registration Dates

• First Submitted: January 17, 2017
• First Submitted That Met QC Criteria: January 17, 2017
• First Posted (Estimated): January 19, 2017

Study Record Updates

• Last Update Posted (Actual): March 21, 2024
• Last Update Submitted That Met QC Criteria: March 20, 2024
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Hydroxychloroquine
• Other Study ID Numbers: Pro00046611

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• 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