Greater Manchester CARDIOvascular Pathology in Immune-Mediated Inflammatory Diseases

NCT ID: NCT06600737

Last Updated: 2024-09-19

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 325 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2024-09-30
• Study Completion Date: 2032-09-01

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.

Detailed Description

Immune-mediated-inflammatory-diseases (IMID) are a range of illnesses affecting over 1 million people in the UK.

Targeted treatments have changed outcomes of common IMIDs, but mortality is still high, largely due to premature cardiovascular disease (CVD). IMID includes the common rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and related conditions, and rare diseases such as systemic sclerosis (SSc), idiopathic inflammatory myopathies (IIM) and vasculitides. Increased risk of CVD and death in IMID contributes to inflammation and cardio metabolic disorders which includes accelerated atherosclerosis, microvascular dysfunction and myocardial and pericardial disease. The research has shown people with RA have a 50% higher risk for CVD than the general population and up to 35% of deaths in patients with SSc are due to cardiac causes.

The biological mechanisms underlying CVD in IMIDs remain largely unknown. Two comparable IMID patients may have significant differences in the presence of CVD and the reasons for this are poorly understood. Despite the significant morbidity and mortality associated with CVD in IMID patients, identification of at-risk patients early in the disease to start treatments and improve prognosis remains challenging. Difficulties also persist in tailoring treatments for people with IMID and existing CVD and there is an evidence gap in treating certain kind of cardiovascular involvement for example, myocarditis. This proposed study will address the missing gaps of the current knowledge. The longitudinal collection and evaluation of routine clinical information and imaging data at different stages of disease will allow the researchers to develop a prognostic model to identify risk factors for CVD in IMID and identify at-risk IMID patients. In addition, the biological and imaging sub-studies will allow the researchers to gain comprehensive insights into the mechanisms underlying CVD in IMID patients, including molecular pathways, genetics and imaging biomarkers. This programme of work will generate important pilot data that will inform subsequent definitive and fully powered studies.

Any potentially eligible patients seen at the relevant rheumatology/cardiology departments as part of in-patient, outpatient and/or multi-disciplinary team meetings and identified as per usual clinical practice may be eligible for inclusion in this observational programme; these patients will be classified as IMID patients at-risk of CVD (IMID-'at risk' CVD), IMID patients with documented new major adverse cardiovascular event (MACE) (Incident IMID-CVD) and IMID patients with previous MACE (Established IMID-CVD). Three groups of control patients will also be recruited; IMID patients with no risk of CVD, patients with CVD but no IMID diagnosis and healthy volunteers.

The doctor will explain to the patient about the study and, if they are interested provide them with the information leaflet.

The participant will have the opportunity to ask the research staff questions after they have seen the paperwork.

Patients may consent same day and/or be given the opportunity to discuss the trial with their family before they are asked whether they would be willing to take part in the trial. If English is not the patient's first language every effort will be made to provide a Trust interpreter according to normal Trust procedures. This is an observational longitudinal study where past, present and future routine clinical data and tests (such as hospital presentations, blood tests, imaging) and/or additional sub-study specific research data will be collected and entered into a database. Following consent, data will be obtained as per usual clinical visits and assessments.

Patients are seen as per standard clinical practice determined by the index IMID and in this setting, also dependent on co-existing CV comorbidity. This would usually be every 6 months at time of IMID/CVD diagnosis and then 12 monthly thereafter. Following consent, data from before this time point may be obtained through the available health records.

Participants will also be asked to complete questionnaires determined by their IMID diagnosis and/or CVD profile at follow up appointments. These will be returned to the University of Manchester along with a registration form that will include confirmation of a participant's contact information. Patients will be given the opportunity to consent to the biological and/or imaging sub-studies. Unlike the main study, participants will be asked to undergo biological tests (blood tests or urine sample if applicable) or imaging tests (echocardiography, cardiac magnetic resonance imaging, peripheral imaging) in addition to routine standard care.

Where possible, these additional tests will be combined with routine clinical care to minimise inconvenience to the participant, for example collecting additional blood tests at same time of routine clinical blood test. The additional imaging studies would need to be done on a separate visit to the routine clinical follow up.

All procedures will be carried out by their local NHS clinical or research team at the Unit they are normally seen in MFT (MRI/Wythenshawe site) based on usual site of care, and will be carried out by trained staff. This is designed to fit around standard care as much as possible and provide as little inconvenience as possible to potential participants.

All control subjects will be treated in the same way patient participants are; The face-to-face consent process will be the same. The research team will explain what is required of them, what procedures they would be undertaking, and the detail of these and where they would occur. Patient-reported outcomes relevant to the IMID and/or CVD profile may be taken at each visit, if the participant consents to this. These may include RAQoL, HAQ, EQ-5D, ScleroID and clinician assessed New York Heart Association (NYHA) classification (based on the patient history). The research staff at the recruiting centre will access participant's medical records, where consent is provided for them to do so. They will enter appropriate research data into an electronic case report form (eCRF) on the hospital site. In the eCRF, participants will be identified by study number only. No personal identifiable information (PII) will be included in the eCRF.

Conditions

Cardiovascular Diseases; Rheumatologic Disease

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

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

No interventions assigned to this group

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

No interventions assigned to this group

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.

No interventions assigned to this group

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

No interventions assigned to this group

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

No interventions assigned to this group

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

No interventions assigned to this group

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

No interventions assigned to this group

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.

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

• 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

• As-listed for Main Study

• As-listed for Main Study

• 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)

Exclusion Criteria

• Age less than 18 years
• Lack of capacity to give informed consent

Imaging Sub-Study

• As-listed for Main Study and;
• For the research cardiac MRI imaging component, the following exclusions will apply: pacemakers, surgical clips within the head, certain inner ear implants, neuro-electrical stimulators or metal fragments within the eye or head, pregnancy or breast-feeding. For administration of gadolinium-based contrast agent, GFR < 30 ml/min/1.73 m2 is a contraindication.

Biological Sub-Study

• As-listed for Main Study

Controls

• As-listed for Main Study and;
• For the research cardiac MRI imaging component, the following exclusions will apply: pacemakers, surgical clips within the head, certain inner ear implants, neuro-electrical stimulators or metal fragments within the eye or head, pregnancy or breast-feeding. For administration of gadolinium-based contrast agent, GFR < 30 ml/min/1.73 m2 is a contraindication.

For Healthy controls:

The researchers will aim to identify healthy controls using the 'bring a friend' strategy where the patient is asked to bring a friend/relative, thus minimising demographic bias. This will establish a healthy control pool. For specific analyses, controls will be age and sex matched and where possible, BMI-matched to the specific study population.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of Manchester

OTHER

Sponsor Role: lead

Responsible Party

Prof. Maya H. Buch

Professor of Rheumatology and Director of Experimental Medicine at the Centre for Musculoskeletal Research, University of Manchester

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Maya H Buch, MD

Role: PRINCIPAL_INVESTIGATOR

University of Manchester

Locations

Manchester University NHS Foundation Trust

Manchester, Greater Manchester, United Kingdom

Site Status: RECRUITING

Countries

United Kingdom

Central Contacts

James Lawrence, MSc

Role: CONTACT

james.lawrence@manchester.ac.uk

+44 161 306 5679

Maya H Buch, MD

Role: CONTACT

maya.buch@manchester.ac.uk

Facility Contacts

Abbie Edwards

Role: primary

abbie.edwards@mft.nhs.uk

Other Identifiers

320989

Identifier Type: -

Identifier Source: org_study_id