Hydroxychloroquine and Cognitive Function After Surgery

NCT03025087 | Terminated Phase 4 Results FDA Drug

• 1 other identifier: Pro00046611
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Individuals Undergoing Cardiac and General Surgery

Outcome Measures

Primary Outcomes (1)

• 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. Ktrans is a constant assessed on the postoperative MRI and has no units of measure.

  Postoperative day 1-5

Study Arms (5)

Phase 1

EXPERIMENTAL

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

Drug: Hydroxychloroquine

Phase 2

EXPERIMENTAL

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

Phase 3

EXPERIMENTAL

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

Phase 4

EXPERIMENTAL

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

Phase 5

EXPERIMENTAL

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

Interventions

Hydroxychloroquine DRUG

Participants will be getting hydroxychloroquine

Phase 1; Phase 2; Phase 3; Phase 4; Phase 5

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Duke University: lead

Study Sites (1)

Duke Health

Durham, North Carolina, 27710, United States

Location

MeSH Terms

Interventions

Hydroxychloroquine

Intervention Hierarchy (Ancestors)

Chloroquine; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Joseph Mathew, MD
• Organization: Duke University

joseph.mathew@duke.edu

919-681-6646

Study Officials

• Joseph P Mathew, MD

  Duke Health

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 17, 2017
• First Posted: January 19, 2017
• Study Start: June 19, 2017
• Primary Completion: May 22, 2023
• Study Completion: April 19, 2024
• Last Updated: August 20, 2024
• Results First Posted: June 12, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)