Hydroxychloroquine and Cognitive Function After Surgery

• Sponsor: Duke University (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT03025087
• Collaborator: (none)
• Enrollment: 30
• Location: 1
• Arms: 5
• Anticipated Duration (Months): 68.4
• Patients Per Site Per Month: 0.4

Study Details

Study Description

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.

Study Design

• Study Type: Interventional
• Anticipated 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: Jun 19, 2017
• Anticipated Primary Completion Date: Mar 1, 2023
• Anticipated Study Completion Date: Mar 1, 2023

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Ratio of T1 relaxivity difference [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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 50 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

1. Female subjects of childbearing potential who have had menstrual period within the past two years

2. Patients with bodily implants unsafe for MRI use

3. Patients with a history of claustrophobia

4. Known or suspected hypersensitivity to quinine (chloroquine or hydroxychloroquine)

5. Patient with pre-existing diagnosis of G6PD deficiency

6. Patients who have participated in another interventional clinical study within the previous 30 days

7. Any other concurrent disease or illness that, in the opinion of the investigator, makes the patient unsuitable for the study

8. 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)

9. Patients who have received chemotherapy in the last 12 months

10. 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Duke Health	Durham	North Carolina	United States	27710

Sponsors and Collaborators

• Duke University

Investigators

• Principal Investigator: Joseph P Mathew, MD, Duke Health

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Duke University
• ClinicalTrials.gov Identifier: NCT03025087
• Other Study ID Numbers: Pro00046611
• First Posted: Jan 19, 2017
• Last Update Posted: Feb 8, 2022
• Last Verified: Jan 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• 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: Hydroxychloroquine

Study Results

No Results Posted as of Feb 8, 2022