Modulating ApoE Signalling to Reduce Brain Inflammation, deLirium and postopErative Cognitive Dysfunction (MARBLE): A Phase 2 Trial to Evaluate the Efficacy and Feasibility of CN-105 in Preventing Postoperative Cognitive Dysfunction and Delirium
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 203
- 试验地点
- 1
- 主要终点
- Number of Adverse Events (AEs) of Grade II or Higher Per Patient
研究概览
简要总结
This research study will evaluate the effectiveness and estimate the feasibility of administering an investigational drug called 'CN-105' (the study drug), to prevent postoperative cognitive decline, delirium (serious confusion) and underlying brain inflammatory and brain activity changes in adults 60 years and older undergoing surgery.
详细描述
This research study will evaluate the effectiveness and estimate the feasibility of administering an investigational drug called 'CN-105' (the study drug), to prevent postoperative cognitive decline, delirium (serious confusion) and underlying brain inflammatory and brain activity changes in adults 60 years and older undergoing surgery. The word "investigational" means the study drug is still being tested in research studies and is not approved by the U.S. Food and Drug Administration (FDA).
It is hoped that CN-105 will block signaling via a gene known as ApoE4, the most common gene implicated in late life Alzheimer's disease.
Depending on when patients enroll in this study, participants will receive either a placebo or a progressively higher dose of CN-105 until the safest and best tolerated dose is reached. The study drug is given via IV (intravenous, meaning through a vein) infusion in the hospital. Study drug infusions will be given up to 4 days after surgery.
Participants will also perform memory and thinking tests, as well as complete a survey and functional assessments, both prior to surgery and again 6 weeks after surgery. Each of those research visits will last about 1 hour.
Additionally, the investigators will collect a blood sample and a cerebrospinal fluid (CSF) sample prior to the participant's surgery, 24 hours after surgery, and again 6 weeks after surgery. To obtain the CSF (cerebrospinal fluid) sample, investigators will perform a lumbar (the lower part of the spinal column) puncture. During surgery, investigators will also record participant brain waves from the scalp using an EEG (electroencephalography) monitor. An electroencephalography monitor reads the electrical activity of the brain in different places using a cap with sensors that is worn on the head.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Participants will be randomized to receive either CN-105 or placebo after they consent to participate in the trial. Participants will be enrolled in 1 of 3 dose cohorts of 67 subjects each. An independent statistician will prepare dose stratified mixed block size randomization lists in a 3 to 1 ratio to achieve the desired distribution of drug and placebo. In each block of 67 trial participants, 50 will receive CN-105 and 17 will receive placebo, in a double-blind fashion.
CN-105 and placebo will be prepared in identical bags labelled simply with the trial participant's number (1-201) to keep all trial staff and clinicians blinded to randomization. Only the investigational pharmacist will have the randomization list for each participant showing what dose of CN-105 or placebo will be administered. To minimize bias, investigators conducting the laboratory assays on the CSF and blood samples will be blinded to trial group assignment during the course of the trial.
入排标准
- 年龄范围
- 60 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Ability to speak English
- •Undergoing non-cardiac, non-neurologic surgical procedures; surgery scheduled to last > 2 hours; due to be admitted to the hospital following surgery
排除标准
- •Inmate of a correctional facility
- •Scheduled to receive systemic chemotherapy between the time of the two cognitive testing sessions
- •Known inability to undergo LPs due to anticoagulant use, severe anxiety, or other clinical contraindication known ahead of time.
- •Inappropriate for study inclusion based on the judgement of the principal investigator.
- •If a patient undergoes major head trauma that occurs between the times of the two cognitive testing sessions, then they will be withdrawn from the study.
研究组 & 干预措施
CN-105
Cohort 1: 50 Patients Dose of CN-105: 0.1 mg/kg
Cohort 2: 50 Patients Dose of CN-105: 0.5 mg/kg
Cohort 3: 50 Patients Dose of CN-105: 1 mg/kg
干预措施: CN-105 (Drug)
Placebo
Cohort 1: 17 Patients receiving placebo
Cohort 2: 17 Patients receiving placebo
Cohort 3: 17 Patients receiving placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Number of Adverse Events (AEs) of Grade II or Higher Per Patient
时间窗: up to 6-week follow-up
Safety of CN-105 administration, as measured by adverse event (AE) rates of Grade II and higher in CN-105 versus placebo-treated patients.
次要结局
- Change in Cerebrospinal Fluid (CSF) IL-6 Cytokine Levels Between Drug vs Placebo Treated Patients(Baseline, 24 hours, approximately 6 weeks)
- Change in CSF IL-8 Cytokine Levels Between Drug vs Placebo Treated Patients(Baseline, 24 hours, approximately 6 weeks)
- Change in CSF MCP-1 Cytokine Levels Between Drug vs Placebo Treated Patients(Baseline, 24 hours, approximately 6 weeks)
- Change in CSF G-CSF Cytokine Levels Between Drug vs Placebo Treated Patients(Baseline, 24 hours, approximately 6 weeks)
- Change in Cognitive Change Index (CCI) Between Drug vs Placebo Treated Patients(Baseline, approximately 6 weeks)
- Feasibility of Drug Administration as Measured by the Percentage of Doses Given Within the Correct Time Window(admission to preoperative holding to hospital discharge (up to postoperative day 4))
- Number of Participants Who Experience Delirium(Baseline, day of surgery (twice), post-operative days 1 - 5 (twice), 6 weeks +/- 3 weeks)
- Peak Severity of Delirium Symptoms Between Drug vs. Placebo Treated Patients(Baseline, day of surgery (twice), post-operative days 1 - 5 (twice), 6 weeks +/- 3 weeks)
研究者
Miles Berger, MD PhD
Assistant Professor, Neuroanesthesiology Division, Anesthesiology Department
Duke University