Hydroxychloroquine and Cognitive Function After Surgery
试验速览
- 阶段
- 4 期
- 状态
- 终止
- 发起方
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Ktrans Volume Transfer Constant
研究概览
简要总结
The purpose of this study is to determine whether hydroxychloroquine decreases the relative leakage of the brain barrier after surgery.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 50 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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)
排除标准
- •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.
研究组 & 干预措施
Phase 1
6 evaluable subjects (3 cardiac, 3 noncardiac patients): 1000 mg HCQ on the day prior to surgery.
干预措施: Hydroxychloroquine (Drug)
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.
干预措施: Hydroxychloroquine (Drug)
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
干预措施: Hydroxychloroquine (Drug)
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.
干预措施: Hydroxychloroquine (Drug)
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.
干预措施: Hydroxychloroquine (Drug)
结局指标
主要结局
Ktrans Volume Transfer Constant
时间窗: 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.
次要结局
未报告次要终点