Pathophysiology and Risk of Atrial Fibrillation Detected After Ischemic Stroke

Atrial Fibrillation Clinical Trial

— PARADISE  

Official title:

The PAthophysiology and Risk of Atrial Fibrillation Detected After Ischemic StrokE (PARADISE): Prospective Non-interventional Cohort Study

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03275155
• Other study ID #: R-17-032
• Status: Active, not recruiting
• Start date: April 18, 2017
• Est. completion date: May 7, 2025

Study information

• Verified date: October 2023
• Source: Lawson Health Research Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 100
• Est. completion date: May 7, 2025
• Est. primary completion date: May 7, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Atrial Fibrillation
• Ischemia
• Ischemic Attack, Transient
• Ischemic Stroke
• Stroke
• Stroke, Ischemic
• Transient Ischemic Attack

Locations

Country	Name	City	State
Canada	University Hospital, London Helath Sciences Center	London	Ontario

Sponsors (6)

Lead Sponsor	Collaborator
Lawson Health Research Institute	El Instituto de Neurociencia Cognitiva y Traslacional (INCYT), Instituto de Neurologia Cognitiva (INECO), London Health Sciences Centre, Parkwood Hospital, London, Ontario, Western University, Canada

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Stroke Recurrence	Number of stroke recurrences in patients with (a) AFDAS , (b) KAF and (c) NSR	At 90, 180, and 360 days
Other	Death	Number of deaths in (a) AFDAS , (b) KAF and (c) NSR groups	At 90, 180, and 360 days
Primary	Changes and Differences in Autonomic Function	Differences in Composite Autonomic Severity Score (CASS) on an 11-point scale between patients with (a) AFDAS, (b) KAF , and (c) NSR	Within 48 hours of stroke onset and at 12, 30 and 90 days.
Primary	Changes and Differences in Inflammatory Responses	Differences in levels of plasma markers or temporal responses (CRP,TNFa, IL-6, IL-1ß, etc) between patients with (a) AFDAS, (b)KAF and (c) NSR.	Within 48 hours of stroke onset and at 12, 30 and 90 days.
Primary	Changes and Differences in Heart Rate Variability (HRV)	Differences in HRV parameters between patients with (a) AFDAS, and (b) NSR	At 14 days.
Secondary	Biomarkers	Differences in levels of plasma markers (BNP,endothelin-1, Lp(a), and TAFI) or neuroimaging/clinical predictors between patients with (a) AFDAS , (b) KAF and (c) NSR	Within 48 hours of stroke onset, at 12, 30 and 90 days and at 6 months.
Secondary	Atrial Fibrillation Burden	Difference in atrial fibrillation burden (sum of atrial fibrillation episodes for a period of time) of AFDAS subjects with mild stroke/TIA compared to AFDAS subjects with moderate/severe stroke.	At 14 days
Secondary	Gait Impairments	Differences in gait parameters in patients with a) AFDAS , (b) KAF and (c) NSR.	At 6 months
Secondary	Frailty	Differences in frailty in patients with (a) AFDAS , (b) KAF and (c) NSR	At 6 months
Secondary	Cognitive Impairment	Differences in cognition in patients with (a) AFDAS , (b) KAF and (c) NSR	At 6 months