Clinical trial NCT03275155: Pathophysiology and Risk of Atrial Fibrillation Detected After Ischemic Stroke
Official title: The PAthophysiology and Risk of Atrial Fibrillation Detected After Ischemic StrokE (PARADISE): Prospective Non-interventional Cohort Study
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Stroke, Ischemic
Transient Ischemic Attack
Atrial Fibrillation
Keywords: Autonomic Dysfunction
Inflammation
Cognitive impairment
Interoception
Gait impairment
Lead sponsor: London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
Sponsor class: OTHER
Collaborators: name: Western University, Canada
name: London Health Sciences Centre
name: Parkwood Hospital, London, Ontario
name: El Instituto de Neurociencia Cognitiva y Traslacional (INCYT)
name: Instituto de Neurologia Cognitiva (INECO)
First posted: 2017-09-07
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Ischemic stroke and transient ischemic attack patients presenting at the University Hospital of the London Health Science Center, London, Ontario, Canada.

Brief summary: This prospective non-interventional cohort study investigates the pathophysiology of Atrial Fibrillation Detected After Stroke or transient ischemic attack (AFDAS) by comparing the autonomic function and inflammation between patients with AFDAS, patients with atrial fibrillation (AF) diagnosed before the ischemic event or known AF (KAF), and patients with normal sinus rhythm (NSR) after 14 day of cardiac monitoring following the event onset.

Detailed description: This study enrolls patients with acute ischemic stroke at the London Health Sciences Center in London, Ontario, Canada. The heart rhythm of the patients is monitored with a CardioSTAT® Holter device (Icentia) for 14 days after the ischemic event onset. Based on this cardiac monitoring and previous medical history, patients are stratified into three groups: (a) atrial fibrillation detected after stroke or transient ischemic attack (AFDAS), (b) atrial fibrillation diagnosed before the ischemic event or known AF (KAF), and (c) normal sinus rhythm (NSR).

Autonomic function is assessed by the levels of plasma catecholamines, a battery of validated autonomic tests \[autonomic reflex screening (ARS)\], heart rate variability (HRV) through data obtained by Holter monitoring by standard quantitative analysis methods according to the guidelines of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology and by the analysis of diurnal variation of heart rate. Blood samples are collected for the analysis of inflammatory markers (e.g. CRP, TNF-α, IL-1β, and IL-6), and potential AFDAS predictors such as brain natriuretic peptide (BNP- AFDAS biomarker), endothelin-1 (endothelial dysfunction marker), Lipoprotein(a) \[Lp(a)\] and thrombin-activatable fibrinolysis inhibitor (TAFI) plasma levels, TAFI activity, TAFI single nucleotide polymorphisms (SNPs), apo(a) isoform size and plasma catecholamines levels. Furthermore, specific neuroimaging findings (e.g., specific regions of the insula or its connections) and clinical features (e.g., impaired interoceptive processing, cognitive impairment, etc) are also analyzed. Interoception is assessed using a heartbeat detection task without feedback condition and gait, balance, frailty, and cognitive status in patients are evaluated by the administration of a battery of tests. Stroke recurrence will be assessed by a structured phone interview at 6 and 12 months after the initial stroke.

Eligibility criteria: Inclusion Criteria:

1. MCA territory-transient ischemic attack or -acute ischemic stroke patients seen in the Emergency Department or admitted to University Hospital, London, Ontario, Canada
2. Age ≥ 18 years old
3. Patient or Substitute Decision Maker must give written informed consent

Exclusion Criteria:

1. Patients with autonomic dysfunction such as Parkinson's disease that can be interfering with outcome assessment based on qualified investigator's judgment.
2. Patients taking tricyclic antidepressant (TCAs)
3. Patients in whom the acute stroke is primarily hemorrhagic
4. Patients with both TIA and atrial fibrillation
5. Patients with both TIA and large vessel disease
6. Patients with inflammatory diseases

Primary outcomes:
measure: Changes and Differences in Autonomic Function
timeFrame: Within 48 hours of stroke onset and at 12, 30 and 90 days.
measure: Changes and Differences in Inflammatory Responses
timeFrame: Within 48 hours of stroke onset and at 12, 30 and 90 days.
measure: Changes and Differences in Heart Rate Variability (HRV)
timeFrame: At 14 days.
Secondary outcomes:
measure: Biomarkers
timeFrame: Within 48 hours of stroke onset, at 12, 30 and 90 days and at 6 months.
measure: Atrial Fibrillation Burden
timeFrame: At 14 days
measure: Gait Impairments
timeFrame: At 6 months
measure: Frailty
timeFrame: At 6 months
measure: Cognitive Impairment
timeFrame: At 6 months
Other outcomes:
measure: Stroke Recurrence
timeFrame: At 90, 180, and 360 days
measure: Death
timeFrame: At 90, 180, and 360 days
Locations:
city: London
country: Canada
facility: University Hospital, London Helath Sciences Center
state: Ontario
Study officials:
affiliation: Lawson Health Research Institute, London Health Sciences Center, Western University
name: Luciano A Sposato, MD
role: PRINCIPAL_INVESTIGATOR
References: