MR Evidence of Cardiac Inflammation Post-Stroke (MIRACLE)

Magnetic Resonance Imaging Evidence of Cardiac Inflammation Post-Stroke

The present study is an investigator initiated, single-centre, prospective, proof-of-concept cohort study aiming to enroll 44 patients with acute middle cerebral artery (MCA) ischemic stroke, involving the right (n=22) and left (n=22) MCA territories and 24 control patients with acute focal neurological symptoms but no evidence of acute brain infarct on DWI-MRI.

Study Overview

• Status: Recruiting
• Conditions: Inflammation; Myocardial Injury; Stroke, Ischemic
• Intervention / Treatment: Diagnostic test: Gadolinium-enhanced cardiac MRI; Diagnostic test: B Natriuretic Peptide; Diagnostic test: Systemic inflammatory markers

Detailed Description

The present study is an investigator-initiated, single-center, prospective cohort study. The study aims to enroll 44 patients with acute/subacute middle cerebral artery (MCA) ischemic stroke. The investigators will compare inflammatory markers among 44 patients with MCA ischemic stroke within 10 days post-stroke vs. 60±15 days post-stroke. Other measures to be determined at both time points include B-Type Natriuretic Peptide and systemic inflammatory markers.

• Study Type: Observational
• Enrollment (Estimated): 44

Contacts and Locations

• Study Contact: Name: Diana Ayan, MSc; Phone Number: 35826 +1 519.685.8500; Email: diana.ayan@lhsc.on.ca
• Study Contact Backup: Name: Jennifer Moussa; Phone Number: 33110 +1 519.685.8500; Email: jennifer.moussa@lhsc.on.ca

Study Locations

• Canada
  • Ontario
    • London, Ontario, Canada, N6A 5A5
      • Recruiting
      • Heart & Brain Lab, Western University
      • Contact: Jennifer Moussa; Phone Number: 33110 +1(519) 685-8500; Email: jennifer.moussa@lhsc.on.ca
      • Contact: Diana Ayan, MSc; Phone Number: 35826 +1(519) 685-8500; Email: diana.ayan@lhsc.on.ca
      • Contact: Luciano Sposato, MD, MBA

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The investigators will include 44 patients with right (n=22) and left (n=22) MCA ischemic stroke. The investigators aim to include at least 50% of female patients. The investigators will include 24 participants in a control group. Participants in the control group will be patients presenting with acute stroke symptoms but no evidence of acute brain infarction on DWI-MRI imaging. Participants will be divided by sex: the investigators aim to enroll 12 female and 12 male participants. The investigators will aim to enroll participants within the same age range as the stroke participants.

Description

Inclusion Criteria:

• Acute ischemic stroke in the right or left MCA territory. Acute ischemic stroke is defined as acute onset focal symptoms matching an acute brain infarct documented on Head computed tomography or diffusion-weighted imaging (DWI) MRI of the brain showing restricted diffusion.

Exclusion Criteria:

• History of known atrial fibrillation, prior myocardial infarction, coronary artery disease, heart failure, prior cardiovascular surgery or percutaneous intervention.
• Previous stroke (occurred within 3 months before the index event)
• Impaired renal function defined as a creatinine clearance <97 mL/min in men or <88 mL/min in women, according to the Cockcroft formula.
• hs-TnT >100 on routine acute stroke baseline bloodwork upon admission.
• Clinically or neurologically unstable patients as per the treating physician.
• Ongoing infection or recent infection within the previous 3 months
• Surgery within 3 months before the stroke
• Concurrent and active inflammatory conditions (connective tissue diseases, rheumatological disease, etc.) or use of anti-inflammatory medications
• Pregnancy, Stage IV renal insufficiency, eGFR <30, and any other contraindications to the use of gadolinium.
• Stroke with symptomatic hemorrhagic transformation
• Subjects will be excluded if they fail the LHSC standard MRI screening questionnaire (cardiac pacemakers/wires, aneurysm clips, shunt/surgical clips, shrapnel/bullets, dentures or metal braces, intra-uterine devices, heart valves, ear implants, prostheses, medication patches such as Nicoderm, Habitrol, or Transderm-Nitro, claustrophobia, history of a head or eye injury involving metal fragments.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Cases (Ischemic stroke): Left and right middle cerebral artery ischemic stroke; Patients presenting with acute onset focal neurological deficits and DWI-MRI evidence of an acute brain infarct of the left or right middle cerebral artery ischemic stroke.	Diagnostic test: Gadolinium-enhanced cardiac MRI; Cardiac magnetic resonance imaging (MRI) with a protocol designed to measure myocardial inflammation and fibrosis.; Diagnostic test: B Natriuretic Peptide; Measurement of B Natriuretic Peptide on patients' blood samples at 10 and 60+/-15 days.; Diagnostic test: Systemic inflammatory markers; Measurement of a panel of 92 systemic inflammatory markers on patients' blood samples at 10 and 60+/-15 days.
Controls (TIA): Patients with acute focal neurological symptoms without brain infarct on MRI.; Patients presenting with acute onset focal neurological deficits presumed to be of vascular origin, WITHOUT DWI-MRI evidence of an acute brain infarct.	Diagnostic test: Gadolinium-enhanced cardiac MRI; Cardiac magnetic resonance imaging (MRI) with a protocol designed to measure myocardial inflammation and fibrosis.; Diagnostic test: B Natriuretic Peptide; Measurement of B Natriuretic Peptide on patients' blood samples at 10 and 60+/-15 days.; Diagnostic test: Systemic inflammatory markers; Measurement of a panel of 92 systemic inflammatory markers on patients' blood samples at 10 and 60+/-15 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The severity of left ventricular myocardial inflammation on cardiac MRI within 10 days post-stroke	Proportion of left ventricular myocardium showing inflammatory changes on gadolinium-enhanced cardiac MRI	Within 10 days of stroke onset
The extent of left ventricular fibrosis measured on gadolinium-enhanced cardiac MRI within 10 days of stroke onset	Proportion of left ventricular myocardium showing fibrosis on gadolinium-enhanced cardiac MRI	Within 10 days of stroke onset

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in left ventricular inflammation measured on gadolinium-enhanced cardiac MRI at 10 and 60±15 days post-stroke	Quantification of left ventricular inflammation measured on gadolinium-enhanced cardiac MRI	At 60±15 days compared to first 10 days
Change in B-Type Natriuretic Peptide (NT-proBNP) levels in the second measurement performed at 60±15 days post-stroke relative to the plasma sample drawn within 10 days.	Change in levels of NT-proBNP between 10 and 60±15 days post-stroke	At 60±15 days compared to first 10 days
Change in systemic inflammatory markers between 10 and 60±15 days post-stroke	High-performance protein biomarker panel for following 92 inflammatory biomarkers in pg/mL ADA; ARTN; AXIN1; NGF; CCL13; CCL19; CCL2; CCL20; CCL23; CCL25; CCL28; CCL3; CCL4; CCL7; CCL8; CXCL10; CXCL11; CXCL5; CXCL6; CXCL9; CDCP1; CASP8; CST5; DNER; CCL11; EIF4EBP1; FGF19; FGF21; FGF23; FGF5; FLT3LG; CX3CL1; GDNF; CXCL1; HGF; IFNG; IL1A; IL10; IL10RA; IL10RB; IL12B; IL13; IL15RA; IL17A; IL17C; IL18; IL18R1; IL2; IL2RB; IL20; IL20RA; IL22RA1; IL24; IL33; IL4; IL5; IL6; IL7; CXCL8; MMP1; KITLG; LIF; LIFR; LTA; CSF1; SIRT2; CD244;NTF3;NRTN;OSM;CD274;S100A12;TGFA;STAMBP;SLAMF1;MMP10;SULT1A1;CD6;CD5;CD8A;TSLP;TGFB1;TNF;TNFSF10;TNFSF11;TNFSF12;TNFSF14;TNFRSF11B;CD40;TNFRSF9;PLAU;VEGFA	At 60±15 days compared to first 10 days
Changes in left atrial inflammation measured on gadolinium-enhanced cardiac MRI at 10 and 60±15 days post-stroke	Quantification of left atrial inflammation measured on gadolinium-enhanced cardiac MRI	At 60±15 days compared to first 10 days
Changes in left atrial fibrosis measured on gadolinium-enhanced cardiac MRI at 10 and 60±15 days post-stroke	Quantification of left atrial fibrosis measured on gadolinium-enhanced cardiac MRI	At 60±15 days compared to first 10 days

Collaborators and Investigators

• Sponsor: Lawson Health Research Institute
• Collaborators: McMaster University; Western University, Canada
• Investigators: Principal Investigator: Luciano Sposato, MD, London Health Sciences Center, Western University

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2021
• Primary Completion (Estimated): June 16, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: January 31, 2022
• First Submitted That Met QC Criteria: February 3, 2023
• First Posted (Actual): February 6, 2023

Study Record Updates

• Last Update Posted (Actual): September 20, 2024
• Last Update Submitted That Met QC Criteria: September 18, 2024
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke; Ischemic Stroke; Inflammation
• Other Study ID Numbers: R-21-323

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No