Biomarkers for Vascular Contributions to Cognitive Impairment and Dementia Consortium
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 入组人数
- 1,892
- 试验地点
- 17
- 主要终点
- SVD progression as measured by decline in global cognition
研究概览
简要总结
Biomarkers for Vascular Contributions to Cognitive Impairment and Dementia (MarkVCID) is an NIH-funded consortium dedicated to finding biomarkers involved in age-related thinking and memory problems. Alzheimer's disease and other dementias leave signatures on brain scans or in the blood called biomarkers. The MarkVCID study will measure a panel of candidate biomarkers in 1800 participants and watch them closely to see what they tell us about changes in brain function and risk of memory loss.
Age-related problems in thinking and memory represent some of the greatest risks to public health in the US and globally. Diseases that affect small blood vessels in the brain have been shown to be major contributors to these changes. However, research and patient care can be held back by limited biomarkers that identify who should be treated.
The MarkVCID Consortium includes 17 US medical centers, a Coordinating Center, an External Advisory Committee, and NIH leadership. Data and biospecimens collected as part of this research study will be stored in a research database and biorepositories, so that researchers can use this information to study brain function.
详细描述
Biomarkers for Vascular Contributions to Cognitive Impairment and Dementia (MarkVCID) is an NIH-funded multisite consortium dedicated to developing promising predictive, diagnostic, target engagement and progression candidate biomarkers of small vessel disease in VCID. MarkVCID is a collaborative consortium of nine North American research sites (consisting of 17 institutions nationwide), a Coordinating Center, External Advisory Committee, and NIH leadership.
MGH serves as the Consortium's Coordinating Center and is comprised of an administrative and data core providing participating research sites with a common support infrastructure that facilitates cross-site collaborations, oversees development of standard operating procedures and data collection methods and manages consortium-wide data.
In phase two of the MarkVCID study, research sites are charged with enrolling and following ≥200 diverse human subjects with cognitive complaints and/or early symptomatic stages of cognitive impairment and dementia potentially associated with cerebrovascular small vessel disease. Sites will share data with the Coordinating Center which will be used for validation studies of chosen consortium biomarkers. Throughout the duration of the study, sites will utilize harmonized procedures and data collection methods to engage in multi-site biomarker validation. Both Cores comply with regulations for the protection of human research subjects (including Good Clinical Practices (GCP), 21 Code of Federal Regulations (CFR)) and with the International Conference on Harmonization (ICH) Regulations E2A and E6.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Prospective
入排标准
- 年龄范围
- 60 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Age ≥ 60 and ≤ 90 years
- •Diagnosis of normal cognition with at least one criterion for vascular risk*, subjective cognitive decline (preliminary diagnosis based on self-report question or eCog-12), mild cognitive impairment, or mild dementia based on standard research criteria
- •Fluent in English or Spanish
- •No contraindications to MRI including CVR
- •No confounding neurologic, psychiatric, or medical disease
- •*Participants with normal cognition must meet at least one criterion (diabetes, OR hypertension plus, OR MRI factors) for vascular risk prior to enrollment:
- •Diabetes (at least one of the following):
- •Fasting (8-hour fast, usually overnight) blood sugar ≥126 mg/dL (≥7 mmol/L, or ≥1260 mg/L)
- •Random or Post-prandial blood sugar ≥200 mg/dL (≥11.11 mmol/L, or ≥2000 mg/L)
- •HbA1C ≥6.5% (or ≥47.5412 mmol/mol)
- •Treatment with an anti-diabetic medicine
- •Hypertension plus (at least two of the following):
- •Use of anti-hypertensive medications for lowering blood pressure for ≥ 10 years
- •Current use of two or more anti-hypertensive medications for lowering blood pressure
- •One measured blood pressure in a research or clinical setting in the last 2 years with SBP ≥140 or DBP ≥90
- •A second measured blood pressure in a research or clinical setting on a different date in the last 2 years with SBP ≥140 or DBP ≥90
- •Evidence of likely HTN end-organ damage (e.g., LVH, albuminuria, eGFR<60, CHF)
- •MRI factors (at least one of the following):
- •Peri-Ventricular Fazekas Extent Grade or Deep Fazekas Extent Grade ≥ 2
- •1 or more microbleeds
- •1 or more lacunar infarcts
排除标准
- •Neurologic Disease: Based on the available data and investigator's impression, exclude those with confounding neurologic disease that would interfere with test performance or with biomarker analysis:
- •Frontotemporal lobar degeneration (FTLD)
- •Lewy body dementia (LBD)
- •Parkinson's disease
- •Multi system atrophy
- •Traumatic brain injury (TBI)-related cognitive impairment
- •TBI that interferes with MRI biomarker analyses (e.g., large volume traumatic lesion)
- •Non-small vessel strokes that interfere with test performance (e.g., post-stroke cognitive impairment or aphasia)
- •Non-small vessel strokes that interfere with MRI biomarker analysis (e.g., large volume strokes)
- •CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy)
- •Individuals known to be receiving, or planning to receive, anti-amyloid immunotherapy*
- •Other neurologic conditions that interfere with test performance or biomarker analysis
- •Individuals prescribed anti-amyloid immunotherapy after MarkVCID enrollment should be kept in the study.
- •Medical and Psychiatric Conditions: Exclude those with medical and psychiatric conditions that would confound the course or interfere with test performance:
- •Schizophrenia or other active/severe psychotic disorders
- •Medical or psychiatric conditions likely to interfere with participation or retention (e.g., metastatic or malignant CNS cancer, active/severe depression or anxiety, HIV- Associated Neurocognitive Disorder)
- •Contraindications to MRI procedures, such as:
- •Claustrophobia
- •Cardiac pacemaker
- •Intracranial clips/metal implants
- •Contraindications to CVR:
- •COPD or other respiratory condition requiring oxygen therapy
- •Asthma or other respiratory condition requiring current use of medications such as inhalers
结局指标
主要结局
SVD progression as measured by decline in global cognition
时间窗: The cognitive battery is implemented, and global cognition calculated, at Baseline and Years 1, 2 and 3 post-baseline.
Global cognition scores will be calculated at each study timepoint as an average of age- and education-specific z-scores, based on tests scores from the MarkVCID2 cognitive battery (MoCA, Neuropsychological Testing Battery, Clinical Dementia Rating), which is based on Version 3 of the National Alzheimer's Coordinating Center's (NACC) Uniform Data Set (UDS) (Besser 2018).
次要结局
- SVD progression as measured by decline in executive function(The cognitive battery is implemented, and executive function calculated, at Baseline and Years 1, 2 and 3 post-baseline.)
研究者
Steven M. Greenberg, MD,PhD
Director, Hemorrhagic Stroke Research
Massachusetts General Hospital