INflammation and Small Vessel Disease Study
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 200
- 试验地点
- 2
- 主要终点
- Peripheral inflammatory markers
研究概览
简要总结
A prospective observational cohort study in patients with cerebral small vessel disease deterring whether changes in systemic inflammation predict brain white matter damage measured using MRI and cognitive decline. This is a study funded by a joint BHF-Dutch Heart Foundation research grant and will be conducted in both Cambridge UK and Nijmegen Netherlands with 100 of the 200 total participants recruited at each site, and data from both sites analysed together.
详细描述
The INSVD study is a prospective observational cohort study in patients with cerebral small vessel disease (SVD) aimed at examining whether changes in systemic inflammation predict brain white matter damage and cognitive decline. This study is funded by a joint British Heart Foundation and Dutch Heart Foundation research grant.
STUDY DESIGN ---------------------------------------------
This study will be conducted at the University of Cambridge (UK) and Radboud University Medical Centre (Nijmegen, Netherlands) with 100 of the 200 total participants recruited at each site.
For the Cambridge arm of the study, patients will be recruited from the clinical stroke service at Cambridge University Hospitals NHS Foundation Trust. Patients will be identified by Professor Hugh Markus (Principal Investigator), Dr Stefania Nannoni and other doctors from their clinics. For the Nijmegen arm, participants will initially be recruited from the RUN DMC cohort, and supplemented with patients from the outpatient clinic of the Neurology department of Radboud University Medical Centre. Patients will be identified by Professor Frank-Erik de Leeuw (Principal Investigator) and other doctors from their clinics. At both sites, electronic hospital records will be used to aid screening and eligibility assessments. In Nijmegen, an ECG and duplex of the carotid arteries are carried out as part of the screening procedure, since data on atrial fibrillation and large artery disease are not always up-to-date or readily available from medical records. Clinicians will check the clinical information and check eligibility against the study criteria. Stroke Research Nurses and Study Coordinators will assist in patient recruitment and receiving consent and collection of baseline data.
Investigators and researchers will ensure that each trial participant is fully informed about the nature and objectives of the trial, and possible risks associated with their participation. Participants will be provided with a Participant Information Sheet explaining the rationale and nature of the study, study procedures and potential benefits and risks of taking part. They will be given an opportunity to ask questions about the study.
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
- 40 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Have given written informed consent to participate
- •Be aged 40 years and over
- •Have symptomatic cerebral small vessel disease (SVD) defined as:
- •Clinical lacunar stroke syndrome with lacunar infarct, as defined by the Standards for Reporting Vascular Changes on Neuroimaging (STRIVE) criteria
- •And/OR Symptoms of cognitive impairment due to SVD with lacunar infarct on MRI
- •And/OR Gait apraxia/motor impairment presumed due to SVD with lacunar infarct on MRI
排除标准
- •Unable/unwilling to consent including lack of capacity to consent
- •Contraindications to taking part in MRI study as assessed by the local MRI safety questionnaire, e.g., pacemaker
- •Vaccination or infection with fever in preceding month
- •Any stroke cause other than SVD including:
- •Cardioembolic source
- •Carotid or vertebral stenosis > 50% measured on NASCET (North American Symptomatic Carotid Endarterectomy Trial) criteria
- •Myocardial infarction in past year
- •Auto-immune/auto-inflammatory disease
- •Use of immunomodulating drugs
- •Estimated glomerular filtration rate (eGFR) =<59 ml/min/1.73m2 within past 3 months for Cambridge, and eGFR =<29 ml/min/1.73m2 within past 3 months for Nijmegen, in line with local guidelines. Estimated GFR will be calculated using the Modification of Diet in Renal Disease (MDRD) equation: 186 x (Creatinine / 88.4)-1.154 x (Age)- 0.203 x (0.742 if female) x (1.210 if black). Creatinine will be checked within 3 months of the MRI, and if this has not been done as part of clinical care it will be performed as a research procedure.
- •Another diagnosed chronic neurological condition (e.g. Alzheimer's, Parkinson's disease, motor neurone disease, multiple sclerosis).
- •Limited life expectancy due to another illness or chronic condition making the 2-year follow-up difficult (e.g. widespread malignancy).
- •Known monogenic cause of small vessel disease (e.g. CADASIL - Cerebral Autosomal Dominant Arteriopathy with Sub-cortical Infarcts and Leukoencephalopathy)
结局指标
主要结局
Peripheral inflammatory markers
时间窗: Baseline (August 2022 - )
Measured from blood sample: a panel of circulating inflammatory proteins. In addition, we will perform extensive phenotyping of peripheral blood mononuclear cells (PBMC) and monocytes, including cytokine production capacity, and transcriptomic and (epi)genetic analyses.
White matter microstructure
时间窗: Baseline + Follow-up (August 2022 - )
Measured by diffusion-weighted imaging: mean diffusivity, fractional anisotropy, peak width of skeletonized mean diffusivity, etc. Diffusion data will be analysed by the creation of voxel by voxel maps of standard diffusion parameters such as mean diffusivity and fraction anisotropy and also by the construction of estimations of white matter tracts using tractography algorithms.
次要结局
- Cognitive performance and decline(Baseline + Follow-up (August 2022 - ))
- Blood brain barrier permeability(Baseline + Follow-up (August 2022 - ))
- Other MRI markers (e.g., brain volume, other measures of SVD)(Baseline + Follow-up (August 2022 - ))
研究者
Hugh Markus
Principal Investigator
University of Cambridge