Lymphatic System Health in Alzheimer's Disease
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 试验地点
- 2
- 主要终点
- T1 fMRI Imagine
研究概览
简要总结
This study hopes to investigate differences in lymphatic health of patients with Alzheimer's disease by analyzing diffusion-weight images in conscious and sleep states. Dexmedetomidine is a short-acting agent that facilitates a sedated state characterized by slow waves and inhibition of norepinephrine. Conceptually, dexmedetomidine may be preferred to other agents, because it is a short-acting norepinephrine blocker, which could mimic slow wave sleep architecture, opening interstitial spaces, and facilitating plaque removal. Dexmedetomidine may also be preferred given its safety profile among the elderly and acutely ill compared to other anesthetic agents. Sleep will be induced with dexmedetomidine, and interstitial fluid convection will be assessed by measuring free-water diffusion imaging. Freewater diffusion imaging separates out the contributions of extracellular free water and water in the vicinity of cellular tissue; it is used to evaluate abnormalities in extracellular space, such as neuroinflammation, which may contribute to long-term cellular degeneration. This method of analysis could be useful in assessing the lymph systems ability to remove extracellular debris.
详细描述
The present study is designed as a prospective data analysis of lymphatic system health in Alzheimer's patients and controls. For Phase I trail, 50 patients of any gender with an age range of 18 to 90 who have undergone the outlined procedure will be recruited for inclusion. Patients will be examined by the principle investigator. All patients will complete neurocognitive testing (QDRS and RBANS) to assess cognitive impairment. A CDR score of 1 or above will be considered dementia. Lumbar punctures will be used to determine Alzheimer's disease status. Patients will be offered the option of participating in the study and provided informed consent for neuroimaging. The subjects will have three fMRI scans: structural T1 and two NOODI DTI scans. The scans take around 45 minutes at no charge to the patients. The dexmedetomidine will be given to the patient after the first DTI scan. The dexmedetomidine dosage will be congruent with patient height, weight, and medical history. This medication will be administered sublingually using an LMA Intranasal Mucosal Atomization Device, which allows the medication to be administered in the form of a spray. Patients will be instructed to keep the medication in their mouth for about 2 minutes, or until fully absorbed. Pulse oximetry and blood pressure will be monitored throughout the duration of treatment. After the subject is asleep, the second DTI scan will be done.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •In order for a subject to be considered for this study, the subject must be willing to comply with the study protocol. They must be between 18 and 90 years old. They must complete neurocognitive testing to assess cognitive impairment (QDRS and RBANS).
排除标准
- •Advanced stages of any terminal illness or any active cancer that requires chemotherapy
- •Hepatic impairment
- •Significant cytopenia
- •Cardiovascular, cerebrovascular, and peripheral vascular arterial thrombosis
- •Women who are pregnant, may become pregnant, or are breastfeeding
- •Any counter indications to dexmedetomidine
- •Subjects unable to give informed consent or in vulnerable categories, such as prisoners
研究组 & 干预措施
Dexmedetomidine
All patients will complete neurocognitive testing inclusive of the Quick Dementia Rating Scale (QDRS) and Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)) to assess cognitive impairment. A Clinical Dementia Rating (CDR) score of 1 or above will be considered dementia. Lumbar punctures will be used to determine Alzheimer's disease status.The subjects will have three fMRI scans: structural T1 and two NOODI DTI scans. The dexmedetomidine will be given to the patient after the first DTI scan with a dosage that will be congruent with patient height, weight, and medical history.
干预措施: Dexmedetomidine (Drug)
结局指标
主要结局
T1 fMRI Imagine
时间窗: Immediately following administration of dexmedetomidine
T1-data was collected as a sagittal MPRAGE sequence. T1 images are corrected for field biasing and then skull stripped and linearly registered to standard MNI space. Each patients' T1 image is segmented into 100 cortical and 15 subcortical areas using the Harvard-Oxford Cortical and Subcortical structural atlas. Mean volume is computed for each of these regions for each patient, which can be used for quantitative comparison.
Diffusion Tensor Imaging
时间窗: Immediately following administration of dexmedetomidine
Diffusion tensor imaging is acquired through diffusion weighted imaging (DWI)-a magnetic resonance techniques that evaluate water diffusion in terms of diffusion constants and diffusion anisotropy. From the acquired DWI, diffusion tensor imaging (DTI) allows us to model the degree of anisotropy and the structural orientation in a quantitative fashion. These DTI fractional anisotropy values will be compared pre and post-treatment.
T1 fMRI Imaging
时间窗: Before dexmedetomidine
T1-data was collected as a sagittal MPRAGE sequence. T1 images are corrected for field biasing and then skull stripped and linearly registered to standard MNI space. Each patients' T1 image is segmented into 100 cortical and 15 subcortical areas using the Harvard-Oxford Cortical and Subcortical structural atlas. Mean volume is computed for each of these regions for each patient, which can be used for quantitative comparison.
次要结局
- Repeatable Battery Assessment of Neuropsychological Status (RBANS) versions A-D(1 week prior to dexmedetomidine)
- Quick Dementia Rating Scale (QDRS)(1 week prior to dexmedetomidine)