A Randomized, Double-Blind, Placebo-Controlled Phase 2 Exploratory Study to Evaluate the Neuroprotective Effects of AV-001 on Hemodialysis-induced Brain Injury Via Cerebrovascular Stabilization in Chronic Hemodialysis Patients
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Evaluate the effect of AV-001 (high dose, low dose) on structural brain injury associated with HD, using MRI as compared to placebo controls.
研究概览
简要总结
Cognitive decline is increasingly recognized among patients receiving maintenance hemodialysis (HD). This can include trouble remembering, slower thinking or mentally feeling foggy.
This research is being done to determine if a new medication (AV-001) can protect the brain from injury caused by hemodialysis by strengthening blood vessels in the brain and reducing inflammation.
If successful, this research could lead to better protection for the brains of people undergoing regular dialysis, potentially reducing the risk of cognitive decline and stroke.
详细描述
Hemodialysis provides life-sustaining treatment for many chronic kidney disease patients around the world. Moderate to severe cognitive impairment is very common in HD patients with up to 70% being affected who are ≥ 55 years of age and ~ 10% in those between 21-39 years of age. Significant cognitive impairment is evident within 6 months of starting HD.
This study is a phase 2 exploratory study in patients receiving hemodialysis treatments. Investigators will recruit 60 patients from the renal program at the London Health Sciences Centre.
Study participants will receive AV-001 (low or high dose) or placebo 60 minutes prior to HD initiation at 3 HD treatment sessions within 1 week (Monday, Wednesday and Friday)
Study participants will also undergo:
- Vital sign collection (blood pressure and heart rate)
- Blood collection
- Cognitive assessments
- Vascular ultrasound
- MRI
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Health Services Research
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Ability to provide informed consent
- •Male and non-pregnant female patients (>18 years old)
- •HD for ≥ 3 months
- •Thrice weekly HD schedule
排除标准
- •HD <90 days
- •Contraindication to MRI
- •Established severe cognitive impairment (Montreal Cognitive Assessment test (MoCA) <18 or formal diagnosis of dementia)
- •Previous clinical stroke
- •Pregnancy, breastfeeding, or intending pregnancy
- •Intradialytic hypotension event (defined as: drop in SBP ≥40mmHg + symptoms + intervention) in previous month as evidenced by HD record
研究组 & 干预措施
Group 1 Placebo
Participants randomized into one group 1placebo. Placebo will be administered 60 minutes prior to hemodialysis initiation, 3 x over a one-week treatment period.
干预措施: AV-001 or Placebo Injection (Drug)
Group 2: AV-001 low dose (12.5μg/kg)
Participants randomized into group 2 will receive AV-001 low dose. AV-001 low dose will be administered 60 minutes prior to hemodialysis initiation, 3 x over a one-week treatment period.
干预措施: AV-001 or Placebo Injection (Drug)
Group 3: AV-001 High Dose (25μg/kg)
Participants randomized into group 3 will receive AV-001 high dose. AV-001 high dose will be administered 60 minutes prior to hemodialysis initiation, 3 x over a one-week treatment period.
干预措施: AV-001 or Placebo Injection (Drug)
结局指标
主要结局
Evaluate the effect of AV-001 (high dose, low dose) on structural brain injury associated with HD, using MRI as compared to placebo controls.
时间窗: Before and after dialysis on study visit day 3.
We will assess brain structure using MRI, allowing accurate detailed study of brain WM structural integrity.
次要结局
- Evaluate circulating biomarkers of vascular injury (S-100β )(Study Visit Day 1 to Study Visit Day 3. (over a 1-week period))
- Evaluate circulatory biomarkers of vascular injury (transthyretin)(Study Visit Day 1 to Study Visit Day 3 (over a 1-week period))
- Evaluate circulatory biomarkers of vascular injury (IL-6)(Study Visit Day 1 to Study Visit Day 3. (over a 1-week period))
- Evaluate circulatory biomarkers of vascular injury (urea)(Study Visit Day 1 to Study Visit Day 3. (over a 1-week period))
- Evaluate circulatory biomarkers of vascular injury (TNF-a)(Study Visit Day 1 to Study Visit Day 3. (over a 1-week period))
- Evaluate circulatory biomarkers of vascular injury (serum lipopolysaccharide)(Study Visit Day 1 to Study Visit Day 3. (over a 1-week period))
- Evaluate circulatory biomarkers of vascular injury (complete blood count)(Study Visit Day 1 to Study Visit Day 3. (over a 1-week period))
- Evaluate circulatory biomarkers of vascular injury (electrolytes)(Study Visit Day 1 to Study Visit Day 3. (over a 1-week period))
- Evaluate circulating biomarkers of vascular injury (dialysate composition)(Study Visit Day 1 to Study Visit Day 3 (over a 1-week period))
- Evaluate circulatory biomarkers of vascular injury (Clot)(Study visit Day 1 to Study Visit Day 3 (over a 1-week period))
- Evaluate circulatory biomarkers of vascular injury (AV-001 specific biomarkers)(Study Visit Day 1 to Study Visit Day 3. (over a 1-week period))
- Evaluate variations in cognitive assessment performance scores using Montreal Cognitive Assessment (MoCA)(Study Visit Day 1 to Study Visit Day 3 (1 week))
- Evaluate variations in cognitive assessment performance scores using Trailsmaking Test A(Study Visit Day 1 to Study Visit Day 3 (1 week))
- Trailsmaking B (TMTB)(Study Visit Day 1 to Study Visit Day 3 (1 week))
- Evaluate variations in cognitive performance scores using Creyos(Study Visit Day 1 to Study Visit Day 3 (1 week))
研究者
Chris McIntyre
MBBS DM
London Health Sciences Centre Research Institute