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.
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
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
HEALTH_SERVICES_RESEARCH
Masking
QUADRUPLE
Enrollment
60
AV-001 or Placebo administered via IV bolus injection.
London Health Sciences Centre
London, Ontario, Canada
RECRUITINGEvaluate the effect of AV-001 (high dose, low dose) on structural brain injury associated with HD, using MRI as compared to placebo controls.
We will assess brain structure using MRI, allowing accurate detailed study of brain WM structural integrity.
Time frame: Before and after dialysis on study visit day 3.
Evaluate circulating biomarkers of vascular injury (S-100β )
Blood Samples (S-100β) will be collected Pre-HD, Peak-HD and Post HD for analysis.
Time frame: Study Visit Day 1 to Study Visit Day 3. (over a 1-week period)
Evaluate circulatory biomarkers of vascular injury (transthyretin)
Blood samples (transthyretin) will be collected Pre-HD, Peak HD and Post HD for analysis.
Time frame: Study Visit Day 1 to Study Visit Day 3 (over a 1-week period)
Evaluate circulatory biomarkers of vascular injury (TNF-a)
Blood Samples (TNF-a) will be collected Pre-HD, Peak-HD and Post HD for analysis
Time frame: Study Visit Day 1 to Study Visit Day 3. (over a 1-week period)
Evaluate circulatory biomarkers of vascular injury (IL-6)
Blood samples (IL-6) will be collected Pre-HD, Peak-HD and Post HD for analysis
Time frame: Study Visit Day 1 to Study Visit Day 3. (over a 1-week period)
Evaluate circulatory biomarkers of vascular injury (serum lipopolysaccharide)
Blood Samples (serum lipopolysaccharide) will be collected Pre-HD, Peak-HD and Post HD for analysis
Time frame: Study Visit Day 1 to Study Visit Day 3. (over a 1-week period)
Evaluate circulatory biomarkers of vascular injury (complete blood count)
Blood Samples (complete blood count) will be collected Pre-HD, Peak-HD and Post HD for analysis.
Time frame: Study Visit Day 1 to Study Visit Day 3. (over a 1-week period)
Evaluate circulatory biomarkers of vascular injury (urea)
Blood Samples (urea) will be collected Pre-HD, Peak-HD and Post HD for analysis.
Time frame: Study Visit Day 1 to Study Visit Day 3. (over a 1-week period)
Evaluate circulatory biomarkers of vascular injury (electrolytes)
Blood Samples (electrolytes) will be collected Pre-HD, Peak-HD and Post HD for analysis.
Time frame: Study Visit Day 1 to Study Visit Day 3. (over a 1-week period)
Evaluate circulating biomarkers of vascular injury (dialysate composition)
Dialysate composition (sodium, potassium, calcium, magnesium, glucose) will be collected Pre-HD, Peak-HD and Post HD for analysis.
Time frame: Study Visit Day 1 to Study Visit Day 3 (over a 1-week period)
Evaluate circulatory biomarkers of vascular injury (Clot)
Blood Samples (clot-troponin T and C-reactive protein) will be collected Pre-HD, Peak-HD and Post HD for analysis.
Time frame: Study visit Day 1 to Study Visit Day 3 (over a 1-week period)
Evaluate circulatory biomarkers of vascular injury (AV-001 specific biomarkers)
AV-001 specific circulatory biomarkers (soluble Tie2, CXCL10, MCP-1, Angiopoietin-1, Angiopoietin-2) will be collected Pre-HD, Peak-HD and Post HD for analysis.
Time frame: 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)
The Montreal Cognitive Assessment (MoCA) is validated and highly sensitive for the detection of mild cognitive impairment and measures short term memory; visuospatial abilities; executive function; attention; concentration and working memory; language; and orientation to time and place.
Time frame: Study Visit Day 1 to Study Visit Day 3 (1 week)
Evaluate variations in cognitive assessment performance scores using Trailsmaking Test A
The Trailsmaking 'A' Test is sensitive to various neurological impairments and provide information on visual search, scanning, speed of processing, mental flexibility and executive functions. The patient is asked to connect numbers 1 through 25 as quickly as possible.
Time frame: Study Visit Day 1 to Study Visit Day 3 (1 week)
Trailsmaking B (TMTB)
The Trailsmaking 'B' Test is sensitive to various neurological impairments and provide information on visual search, scanning, speed of processing, mental flexibility and executive functions. Patients are asked to alternate numbers and letters which requires thinking flexibility and mental shifting.
Time frame: Study Visit Day 1 to Study Visit Day 3 (1 week)
Evaluate variations in cognitive performance scores using Creyos
Creyos encompass assessments of short-term memory, reasoning, attention and verbal ability. Creyos is an online platform and will be completed on a study designated tablet.
Time frame: Study Visit Day 1 to Study Visit Day 3 (1 week)
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