Greater Manchester CARDIOvascular Pathology in Immune-Mediated Inflammatory Diseases
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 325
- 试验地点
- 1
- 主要终点
- Number of participants with major adverse cardiovascular events (MACE)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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
排除标准
- •Age less than 18 years
- •Lack of capacity to give informed consent
- •Imaging Sub-Study
- •Inclusion Criteria:
- •As-listed for Main Study
- •Exclusion Criteria:
- •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
- •Inclusion Criteria:
- •As-listed for Main Study
- •Exclusion Criteria:
- •As-listed for Main Study
- •Inclusion Criteria:
- •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:
- •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.
结局指标
主要结局
Number of participants with major adverse cardiovascular events (MACE)
时间窗: 10 Years
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
次要结局
- 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)
- Number of participants with abnormal N-terminal pro B-type natriuretic peptide (NT-pro BNP) levels(10 Years)
- Number of participants with abnormal Creatine Kinase (CK) levels(10 Years)
研究者
Prof. Maya H. Buch
Professor of Rheumatology and Director of Experimental Medicine at the Centre for Musculoskeletal Research, University of Manchester
University of Manchester