Greater Manchester CARDIOvascular Pathology in Immune-Mediated Inflammatory Diseases

NCT06600737 | Recruiting

• 1 other identifier: 320989
• Study Type: observational
• Target: 325
• Locations: 1 country
• Sites: 1

Brief Summary

The researchers would like to know more about cardiovascular abnormalities in patients with immune-mediated inflammatory diseases (IMID) and with the aim to provide new biomarkers (clinical, blood, imaging) for early diagnosis, prognosis and prediction of CVD in patients with IMID. This is important as there are still many things that are not known about this and finding out more could improve how patients are treated in future. Participants with IMID diagnoses will be recruited from rheumatology/cardiology departments as in-patients or outpatients. Once consented, researchers will collect past, present and future clinical information about them, including routine cardiovascular imaging and blood tests. Participants will also be asked to complete questionnaires at predetermined intervals. The participants could also be approached to take part in the following sub-studies; Biological sub-study, in which blood and urine would be collected; And the Imaging-sub study, in which one or more of Echocardiography, Cardiovascular Magnetic Resonance Imaging (CMR) and Laser Doppler Imaging (LDI) will be performed. Participants with CVD without IMID and healthy volunteers will also be recruited as comparison groups. The research is to be funded by the NIHR Manchester BRC ('Integrated Cardiovascular' and 'Rheumatic \& Musculoskeletal Diseases' themes). Other funding eg Manchester Academic Health Sciences and a recently awarded Medical Research Council Partnership grant will also support this programme. The study will recruit in specialist NHS centres; Recruitment will start in Manchester University Hospitals NHS Foundation Trust.

Conditions

Cardiovascular Diseases; Rheumatologic Disease

Outcome Measures

Primary Outcomes (1)

• Number of participants with major adverse cardiovascular events (MACE)

  Major Adverse Cardiovascular Events (MACE) is a grouped term typically defined as acute myocardial infarction, stroke or cardiovascular death. Primary myocardial events such as myocarditis (especially relevant to IMIDs such as SSc, IIM, SLE) will also form part of the primary MACE definition. The total number of participants presenting with or developing a MACE will be measured. Unit: number of participants

  10 Years

Secondary Outcomes (7)

• Number of participants with heart failure hospitalisations

  10 Years

• Number of participants with unstable angina

  10 Years

• Number of participants needing revascularisation

  10 Years

• Number of participants with abnormal high-sensitivity cardiac troponin I/T levels

  10 Years

• Number of participants with abnormal ECHO and or CMR imaging measures

  10 Years

Study Arms (8)

Disease Control (IMID and no CV disease)

Control subjects will be asked to consent to a limited routine clinical, laboratory and imaging assessment and separate consent will be sought for imaging and biological sample collection. Consent for genetic (DNA) sample collection will be sought separately also. Where indicated, two groups of disease control patients will be recruited: (i) patients with an IMID and no CV disease and (ii) patients with CVD and no IMID diagnosis. The following assessments will be conducted (if indicated as part of a participants standard care): Clinician Questionnaires Clinical/medical, health and social care and social determinants Routine laboratory assessments Routine cardiovascular imaging and electrophysiology assessments Investigations to evaluate for cardiac conduction abnormalities and arrythmia may also be performed as part of routine care Routine peripheral vascular imaging assessment Patient reported outcome measures (PROMs) Questionnaires

Disease Control (CV disease and no IMID)

Control subjects will be asked to consent to a limited routine clinical, laboratory and imaging assessment and separate consent will be sought for imaging and biological sample collection. Consent for genetic (DNA) sample collection will be sought separately also. Where indicated, two groups of disease control patients will be recruited: (i) patients with an IMID and no CV disease and (ii) patients with CVD and no IMID diagnosis. The following assessments will be conducted (if indicated as part of a participants standard care): Clinician Questionnaires Clinical/medical, health and social care and social determinants Routine laboratory assessments Routine cardiovascular imaging and electrophysiology assessments Investigations to evaluate for cardiac conduction abnormalities and arrythmia may also be performed as part of routine care Routine peripheral vascular imaging assessment Patient reported outcome measures (PROMs) Questionnaires

Healthy Control (no IMID history or CV disease)

Control subjects will be asked to consent to a limited routine clinical, laboratory and imaging assessment and separate consent will be sought for imaging and biological sample collection. Consent for genetic (DNA) sample collection will be sought separately also. Healthy Control participants will have a limited number of assessments performed which may include: * Demographics, employment * Medical history, diagnoses, co-morbidities, symptoms, signs, lifestyle (smoking status (pack years) and alcohol intake (units/week), CVD risk scores * Detailed family history of autoimmune, vascular and rheumatic disease * Medications, vaccinations * Physical status (e.g. height and weight, blood pressure), IMID disease activity assessment as indicated * Data on hospital attendances and admissions, MACE, death registry information.

Main Study (IMID 'at risk' CVD)

Individuals who have a risk of developing CVD (based on traditional risk factors and/or IMID-specific factors) but no history of major adverse cardiovascular events (MACE). The main study represents standard clinical care and includes the routine clinical, laboratory and imaging assessments. Patients may be recruited at any point along their CVD continuum (eg when considered at risk, at time of or after a diagnosis of a CVD). The following assessments will be conducted (if indicated as part of a participants standard care): Clinician Questionnaires Clinical/medical, health and social care and social determinants Routine laboratory assessments Routine cardiovascular imaging and electrophysiology assessments Investigations to evaluate for cardiac conduction abnormalities and arrythmia may also be performed as part of routine care Routine peripheral vascular imaging assessment Patient reported outcome measures (PROMs) Questionnaires

Main Study (Incident (new) IMID-CVD)

Patients with IMID that present with a MACE. The main study represents standard clinical care and includes the routine clinical, laboratory and imaging assessments. Patients may be recruited at any point along their CVD continuum (eg when considered at risk, at time of or after a diagnosis of a CVD). The following assessments will be conducted (if indicated as part of a participants standard care): Clinician Questionnaires Clinical/medical, health and social care and social determinants Routine laboratory assessments Routine cardiovascular imaging and electrophysiology assessments Investigations to evaluate for cardiac conduction abnormalities and arrythmia may also be performed as part of routine care Routine peripheral vascular imaging assessment Patient reported outcome measures (PROMs) Questionnaires

Main Study (Established IMID-CVD)

Patients with IMID and a history of previous MACE. The main study represents standard clinical care and includes the routine clinical, laboratory and imaging assessments. Patients may be recruited at any point along their CVD continuum (eg when considered at risk, at time of or after a diagnosis of a CVD). The following assessments will be conducted (if indicated as part of a participants standard care): Clinician Questionnaires Clinical/medical, health and social care and social determinants Routine laboratory assessments Routine cardiovascular imaging and electrophysiology assessments Investigations to evaluate for cardiac conduction abnormalities and arrythmia may also be performed as part of routine care Routine peripheral vascular imaging assessment Patient reported outcome measures (PROMs) Questionnaires

Imaging Sub-Study

In addition to the main study, patients will be offered the opportunity to consent to participate in the imaging Sub-Study. Patients consenting to the Imaging Sub-Study must also have consented to participate in the Main Study. Assessments conducted as part of the Main Study are outlined in the relevant 'Main Study' Group/Cohort descriptions. Individuals participating in the Imaging Sub-Study may be asked to undergo additional imaging tests above standard of care (undertaken separately to the main study assessments/visits) using dedicated research protocols. The following assessments may be conducted: Echocardiography Cardiovascular Magnetic Resonance Imaging (CMR) Peripheral vascular imaging techniques: Laser Doppler Imaging (LDI) and laser speckle contrast imaging (LSCI) Nailfold capillaroscopy Multispectral imaging Non-vascular skin imaging techniques: High frequency ultrasound

Biological Sub-Study

In addition to the Main Study, patients will be offered the opportunity to consent to participate in the Biological Sub-Study. Patients consenting to the Biological Sub-Study must also have consented to participate in the Main Study. Assessments conducted as part of the Main Study are outlined in the relevant 'Main Study' Group/Cohort descriptions. Biological samples as part of the Sub-Study are in addition to standard of care blood samples. A maximum of 75mls of blood may be taken to enable the range of experimental studies. The samples may be taken at initial time of recruitment (baseline) and/or may be repeated at certain time points depending on the diagnosis and if a change in the clinical status (excluding genotyping). The blood may be drawn into a combination of EDTA, lithium heparin, red clotted, citrate and PAXGENE/TEMPUS tubes, according to planned experiments at each time point.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Participants will be recruited from NHS secondary care in the United Kingdom. Potential participants may be identified from clinics, wards, diagnostic pathways and departments, electronic and paper-based health records, databases and waiting lists in secondary care. All individuals will be considered for inclusion in this study regardless of age, disability, gender reassignment, marriage and civil partnership, pregnancy and maternity, race, religion and belief, sex, and sexual orientation, except where the study inclusion and exclusion criteria explicitly state otherwise.

You may qualify if:

• Males and females
• Subjects aged over 18 years
• Capable of providing informed consent and signing a consent form
• Have a clear diagnosis of an IMID with history consistent with one of the following categories:
• IMID-'at risk' CVD: individuals who have a risk of developing CVD (based on traditional risk factors and/or IMID-specific factors) but no history of major adverse cardiovascular events (MACE).
• Incident (new) IMID-CVD: Patients with IMID that present with a MACE.
• Established IMID-CVD: Patients with IMID and a history of previous MACE

You may not qualify if:

• Age less than 18 years
• Lack of capacity to give informed consent
• Imaging Sub-Study
• \- As-listed for Main Study
• As-listed for Main Study and;
• Biological Sub-Study
• \- As-listed for Main Study
• \- As-listed for Main Study
• Controls
• Subject ≥ 18 years of age
• Is capable of understanding and signing an informed consent form
• No known diagnosis of an IMID (CVD-no IMID disease control and healthy control groups)
• No known diagnosis of CVD (IMID-no risk CVD disease control and healthy control groups)
• As-listed for Main Study and;
• For Healthy controls:

Sponsors & Collaborators

• University of Manchester: lead

Study Sites (1)

Manchester University NHS Foundation Trust

Manchester, Greater Manchester, M13 9WL, United Kingdom

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

In total, 5 blood tubes (x1 plasma, x1 serum and x3 EDTA tube) will be collected, but if the maximum 75mls is needed additional blood tubes will be used. The blood samples may include peripheral blood mononuclear cells. Patients will have the opportunity to consent separately to a genetic (DNA) component. These samples will be collected during a participant's routine clinical appointment at the hospital by their clinical care or research team.

MeSH Terms

Conditions

Cardiovascular Diseases; Collagen Diseases

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases

Study Officials

• Maya H Buch, MD

  University of Manchester

  PRINCIPAL INVESTIGATOR

Central Study Contacts

James Lawrence, MSc

CONTACT

+44 161 306 5679; james.lawrence@manchester.ac.uk

Maya H Buch, MD

CONTACT

maya.buch@manchester.ac.uk

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 10 Years
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Rheumatology and Director of Experimental Medicine at the Centre for Musculoskeletal Research, University of Manchester

Study Record Dates

• First Submitted: September 10, 2024
• First Posted: September 19, 2024
• Study Start: September 30, 2024
• Primary Completion (Estimated): September 1, 2032
• Study Completion (Estimated): September 1, 2032
• Last Updated: September 19, 2024

Record last verified: 2024-09

Locations

GB (1)