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出境医 / 临床实验 / Magnetic Resonance Imaging (MRI) for Aortic Dissection to Visualise Inflammation

Magnetic Resonance Imaging (MRI) for Aortic Dissection to Visualise Inflammation

Study Description
Brief Summary:
The study is a single-centre, prospective, observational cross-sectional imaging study aimed to determine if macrophage-mediated inflammation can be visualised in the aorta of patients with aortic dissection (AD) using ultrasmall super paramagnetic iron oxides (USPIO)-enhanced magnetic resonance imaging (MRI).

Condition or disease Intervention/treatment
Aortic Dissection Aortic Diseases Diagnostic Test: Magnetic Resonance Imaging (MRI) using ultrasmall super paramagnetic iron oxides (USPIOs)

Detailed Description:

Aortic dissection (AD) is a condition in which a disruption of the medial layer (in most cases provoked by a tear or an ulcer in the intima) results in separation of the aortic wall layers, with concomitant 'false lumen' formation and malperfusion of end organs.

The underlying mechanism of the condition has, until recently, remained unclear. The Pi of the present sutdy has shed light on a mechanism that shows that inflammation underlies the condition. The PI of the present study has showed that inflammation in the aorta is triggered by macrophage infiltration into the aortic wall in both pre-clinical models using animal models of the condition (murine) and in patient tissue samples obtained at time of surgery.

Macrophage infiltration into the aortic wall, as a result of activation of the cytokine, granulocyte-macrophage colony stimulating factor (GM-CSF), is the trigger for an inflammatory cascade that is presently understood to underlie the pathogenic mechanism of the condition

Non-invasive assessment of macrophage infiltration would prove that this pathogenic mechanism exists (proof-of-concept). Macrophage infiltration has been shown to be feasible by contrast-enhanced Magnetic Resonance Imaging (MRI) using ultrasmall super paramagnetic iron oxides (USPIOs).

The hypothesis of the present study is that macrophage-mediated inflammation can be visualised in the aorta of patients with AD using the USPIO-enhanced MRI technique, and use the present study to confirm this (proof-of-concept).

Study Design
Layout table for study information
Study Type : Observational
Estimated Enrollment : 20 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Magnetic Resonance Imaging (MRI) for Aortic Dissection to Visualise Inflammation
Actual Study Start Date : September 11, 2019
Estimated Primary Completion Date : March 31, 2022
Estimated Study Completion Date : March 31, 2022
Arms and Interventions
Group/Cohort Intervention/treatment
Acute aortic dissection
stable patients with confirmed diagnosis of acute AD.
Diagnostic Test: Magnetic Resonance Imaging (MRI) using ultrasmall super paramagnetic iron oxides (USPIOs)
All patients will undergo two MRI scans (one MRI scan pre-USPIO administration, and one MRI scan 24-36 hours following USPIO administration) and blood samples will be taken for future biomarker analysis.

Chronic aortic dissection
patients with diagnosis of chronic AD, being followed up in outpatient aortic clinic.
Diagnostic Test: Magnetic Resonance Imaging (MRI) using ultrasmall super paramagnetic iron oxides (USPIOs)
All patients will undergo two MRI scans (one MRI scan pre-USPIO administration, and one MRI scan 24-36 hours following USPIO administration) and blood samples will be taken for future biomarker analysis.

Outcome Measures
Primary Outcome Measures :
  1. Visualisation of inflammation [ Time Frame: Up to 36 hours ]
    To determine if macrophage-mediated inflammation can be visualised in the aorta of patients with aortic dissection using USPIO-enhanced MRI

  2. Feasibility [ Time Frame: Up to 36 hours ]
    To establish the feasibility of imaging macrophage-mediated inflammation in the aorta of patients with aortic dissection, using USPIO-enhanced MRI.


Secondary Outcome Measures :
  1. Timing [ Time Frame: Up to 36 hours ]
    To determine the timing of macrophage infiltration in aortic dissection (acute or chronic phase)

  2. Localisation [ Time Frame: Up to 36 hours ]
    To assess if macrophage mediated inflammation is localised to the site of dissection and the surrounding aorta or more widespread in the vasculature.


Biospecimen Retention:   Samples Without DNA
Blood samples

Eligibility Criteria
Layout table for eligibility information
Ages Eligible for Study:   40 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Acute patients will be identified in cardiologic inward, after that patients have been discharged from the coronary care unit at Glenfield Hospital, Leicester. Chronic patients will be identified from the aortic outpatient clinic at Glenfield Hospital.
Criteria

Inclusion Criteria:

  • Confirmed diagnosis of acute or chronic aortic dissection (>2 week after initial intimal injury)
  • Able and willing to comply with all study requirements.
  • Age > 40 years (Patients under the age of 40 years will not be included as they may have a connective tissue disorder accounting for their condition)
  • Able and willing to give informed consent
  • An adequate understanding of written and verbal English

Exclusion Criteria:

  • Past history of systemic iron overload or haemochromatosis
  • Renal failure (estimated glomerular filtration rate < 30ml/min)
  • Contraindication to MRI
  • Known allergy to iron-containing compounds
  • Participants who have participated in another research study involving an investigational product in the past 12 weeks.
  • Female participants who are pregnant or lactating.
  • Unwilling or unable to give informed consent
Contacts and Locations

Contacts
Layout table for location contacts
Contact: Andrea Salzano, MD +44 (0) 1162583041 andrea.salzano@leicester.ac.uk
Contact: Toru Suzuki, MD, PhD +44 (0)116 204 4741 tsuzuki@leicester.ac.uk

Locations
Layout table for location information
United Kingdom
University of Leicester Not yet recruiting
Leicester, United Kingdom, LE3 9QP
Contact: Andrea Salzano, MD       andrea.salzano@leicester.ac.uk   
Contact: Toru Suzuki, PhD       tsuzuki@leicester.ac.uk   
Sub-Investigator: Gerry P McCann, MD         
Sub-Investigator: Anvesha Singh, PhD         
University Hospitals of Leicester NHS Trust Recruiting
Leicester, United Kingdom
Contact: Prof Suzuki         
Sponsors and Collaborators
University of Leicester
Investigators
Layout table for investigator information
Study Chair: Toru Suzuki, MD, PhD University of Leicester
Tracking Information
First Submitted Date May 7, 2019
First Posted Date May 14, 2019
Last Update Posted Date May 3, 2021
Actual Study Start Date September 11, 2019
Estimated Primary Completion Date March 31, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: May 9, 2019)
  • Visualisation of inflammation [ Time Frame: Up to 36 hours ]
    To determine if macrophage-mediated inflammation can be visualised in the aorta of patients with aortic dissection using USPIO-enhanced MRI
  • Feasibility [ Time Frame: Up to 36 hours ]
    To establish the feasibility of imaging macrophage-mediated inflammation in the aorta of patients with aortic dissection, using USPIO-enhanced MRI.
Original Primary Outcome Measures Same as current
Change History
Current Secondary Outcome Measures
 (submitted: May 9, 2019)
  • Timing [ Time Frame: Up to 36 hours ]
    To determine the timing of macrophage infiltration in aortic dissection (acute or chronic phase)
  • Localisation [ Time Frame: Up to 36 hours ]
    To assess if macrophage mediated inflammation is localised to the site of dissection and the surrounding aorta or more widespread in the vasculature.
Original Secondary Outcome Measures Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Magnetic Resonance Imaging (MRI) for Aortic Dissection to Visualise Inflammation
Official Title Magnetic Resonance Imaging (MRI) for Aortic Dissection to Visualise Inflammation
Brief Summary The study is a single-centre, prospective, observational cross-sectional imaging study aimed to determine if macrophage-mediated inflammation can be visualised in the aorta of patients with aortic dissection (AD) using ultrasmall super paramagnetic iron oxides (USPIO)-enhanced magnetic resonance imaging (MRI).
Detailed Description

Aortic dissection (AD) is a condition in which a disruption of the medial layer (in most cases provoked by a tear or an ulcer in the intima) results in separation of the aortic wall layers, with concomitant 'false lumen' formation and malperfusion of end organs.

The underlying mechanism of the condition has, until recently, remained unclear. The Pi of the present sutdy has shed light on a mechanism that shows that inflammation underlies the condition. The PI of the present study has showed that inflammation in the aorta is triggered by macrophage infiltration into the aortic wall in both pre-clinical models using animal models of the condition (murine) and in patient tissue samples obtained at time of surgery.

Macrophage infiltration into the aortic wall, as a result of activation of the cytokine, granulocyte-macrophage colony stimulating factor (GM-CSF), is the trigger for an inflammatory cascade that is presently understood to underlie the pathogenic mechanism of the condition

Non-invasive assessment of macrophage infiltration would prove that this pathogenic mechanism exists (proof-of-concept). Macrophage infiltration has been shown to be feasible by contrast-enhanced Magnetic Resonance Imaging (MRI) using ultrasmall super paramagnetic iron oxides (USPIOs).

The hypothesis of the present study is that macrophage-mediated inflammation can be visualised in the aorta of patients with AD using the USPIO-enhanced MRI technique, and use the present study to confirm this (proof-of-concept).

Study Type Observational
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples Without DNA
Description:
Blood samples
Sampling Method Probability Sample
Study Population Acute patients will be identified in cardiologic inward, after that patients have been discharged from the coronary care unit at Glenfield Hospital, Leicester. Chronic patients will be identified from the aortic outpatient clinic at Glenfield Hospital.
Condition
  • Aortic Dissection
  • Aortic Diseases
Intervention Diagnostic Test: Magnetic Resonance Imaging (MRI) using ultrasmall super paramagnetic iron oxides (USPIOs)
All patients will undergo two MRI scans (one MRI scan pre-USPIO administration, and one MRI scan 24-36 hours following USPIO administration) and blood samples will be taken for future biomarker analysis.
Study Groups/Cohorts
  • Acute aortic dissection
    stable patients with confirmed diagnosis of acute AD.
    Intervention: Diagnostic Test: Magnetic Resonance Imaging (MRI) using ultrasmall super paramagnetic iron oxides (USPIOs)
  • Chronic aortic dissection
    patients with diagnosis of chronic AD, being followed up in outpatient aortic clinic.
    Intervention: Diagnostic Test: Magnetic Resonance Imaging (MRI) using ultrasmall super paramagnetic iron oxides (USPIOs)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Recruiting
Estimated Enrollment
 (submitted: May 9, 2019)
20
Original Estimated Enrollment Same as current
Estimated Study Completion Date March 31, 2022
Estimated Primary Completion Date March 31, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion Criteria:

  • Confirmed diagnosis of acute or chronic aortic dissection (>2 week after initial intimal injury)
  • Able and willing to comply with all study requirements.
  • Age > 40 years (Patients under the age of 40 years will not be included as they may have a connective tissue disorder accounting for their condition)
  • Able and willing to give informed consent
  • An adequate understanding of written and verbal English

Exclusion Criteria:

  • Past history of systemic iron overload or haemochromatosis
  • Renal failure (estimated glomerular filtration rate < 30ml/min)
  • Contraindication to MRI
  • Known allergy to iron-containing compounds
  • Participants who have participated in another research study involving an investigational product in the past 12 weeks.
  • Female participants who are pregnant or lactating.
  • Unwilling or unable to give informed consent
Sex/Gender
Sexes Eligible for Study: All
Ages 40 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts
Contact: Andrea Salzano, MD +44 (0) 1162583041 andrea.salzano@leicester.ac.uk
Contact: Toru Suzuki, MD, PhD +44 (0)116 204 4741 tsuzuki@leicester.ac.uk
Listed Location Countries United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number NCT03948555
Other Study ID Numbers 0688
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement
Plan to Share IPD: No
Responsible Party University of Leicester
Study Sponsor University of Leicester
Collaborators Not Provided
Investigators
Study Chair: Toru Suzuki, MD, PhD University of Leicester
PRS Account University of Leicester
Verification Date April 2021