Comprehensive Multimodal Analysis of Patients With Neuroimmunological Diseases of the CNS
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 2,400
- 试验地点
- 1
- 主要终点
- Disease progression as assessed by clinical and MRI criteria.
研究概览
简要总结
Inflammatory or degenerative diseases of the brain and spinal cord, such as multiple sclerosis, may be related to problems with an individual s immune system. However, more information is needed on the ways in which the cells of the immune system interact with the central nervous system (CNS). This study will compare tests performed on both healthy volunteers and individuals who have signs or symptoms of immune-related damage to their CNS.
This study will include two groups of subjects at least 12 years old. Subjects will either have symptoms of immune-related CNS damage, or will be healthy volunteers selected for comparison purposes.
Study participants will visit the NIH Clinical Center on an outpatient basis for an initial evaluation visit. During the visit, patients will provide a comprehensive medical history and undergo a neurological examination, and will provide blood samples for research purposes. The healthy volunteers will be asked to schedule a return visit for a magnetic resonance imaging (MRI) procedure, and may be asked to undergo other tests requested by the study researchers on an as-needed basis. The group of patients with symptoms of immune-related CNS damage will be asked to undergo a series of tests, including the following:
- MRI procedures, with a minimum of three brain MRIs and one spinal cord MRI taken approximately 4 weeks apart
- A diagnostic lumbar puncture, performed on an outpatient basis
- Tests of brain and vision activity
- Additional blood and tissue samples
Patients with symptoms of immune-related CNS damage may be offered the opportunity to participate in additional followup tests with NIH researchers.
详细描述
OBJECTIVE
The goal of this study is to define the pathophysiological mechanisms underlying the development of disability in immune-mediated disorders of the central nervous system (CNS) and to distinguish these from beneficial responses of the human immune system to CNS injury.
The protocol serves as a screening tool for Neuroimmunological Diseases Section (NDS) of the National Institute of Allergy and Infectious Diseases (NIAID) clinical trials and enables development of clinically-useful tools such as diagnostic tests and new, sensitive scales of neurological disability, disease severity and CNS tissue destruction.
This protocol also serves as a repository to enable prospective institutional review board (IRB) review of research using human samples and data collected under other NDS protocols.
STUDY POPULATION
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
- 1 Month 至 99 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •PATIENT INCLUSION CRITERIA (for in-person and telemedicine sub-cohorts):
- •Presentation with a clinical syndrome consistent with immune-mediated CNS disorder and/or
- •Neuroimaging evidence of inflammatory and/or demyelinating/dysmyelinating CNS disease
- •At least 12 years old at the time of enrollment
- •Willing to share medical records (including past MRI results) with the study team.
- •Adults: Able to give informed consent on their own or via a Legally Authorized Representative (LAR) or Durable Power of Attorney (DPA); or Minors: parent or legal guardian able to give consent, with child willing to give assent, if reasonable based on their age and assent capacity
- •For in-person sub-cohort: Able to undergo the required procedures, including LP, MRI and clinical/functional evaluations
排除标准
- •(for in-person and telemedicine sub-cohorts):
- •Significant medical condition that would make participation in research part of evaluation impossible or risky
- •For in-person sub-cohort: Medical contraindications for MRI (i.e. any non-organic implant or other device such as a cardiac pacemaker or infusion pump or other metallic implants, objects or body piercings that cannot be removed)
- •Unwilling to consent for collection of biological samples or their cryopreservation
- •PATIENT INCLUSION CRITERIA for processing of collected biological samples:
- •Presentation with a clinical syndrome consistent with immune-mediated CNS disorder and/or
- •Neuroimaging evidence of inflammatory and/or demyelinating/ dysmyelinating CNS disease
- •Ability to obtain either direct or surrogate informed consent for sample processing and storage
- •Aged 0+ years
- •HEALTHY VOLUNTEER (in person) INCLUSION CRITERIA:
- •At least 18 years old at the time of enrollment
- •Vital signs are found within normal range at the time of the screening visit
- •Able to give informed consent
- •Able and willing to undergo related research procedures, such as blood draw, LP
- •HEALTHY VOLUNTEER (in person) EXCLUSION CRITERIA:
- •Systemic inflammatory disorder, or inflammatory or non-inflammatory neurological diseases
- •Previous or current history of alcohol and substance abuse
- •Medical contraindications for MRI (i.e. any non-organic implant or other device such as a cardiac pacemaker or infusion pump or other metallic implants, objects or body piercings that cannot be removed)
- •Medical contraindication for LP
- •Psychological contraindications for MRI (i.e. claustrophobia). This will be assessed at the time the medical history is collected
- •Pregnancy or current breastfeeding
- •Any contraindications to having study procedures done
- •History of auditory disorder (i.e. hearing impairment, known impaired acoustic reflex, tinnitus)
- •HEALTHY VOLUNTEER SUB-STUDY TO OBTAIN NORMATIVE DATA FOR THE SMARTPHONE APPS:
- •Because this sub-study collects no personal identifiable information (PII), there are no inclusion/exclusion criteria. Participating subjects are self-declared as not having any neurological deficit, which would be the same population that would provide normative data if the apps were freely available via App store.
研究组 & 干预措施
Patient Cohort
Patients who present with CNS white matter injury (including inflammatory and/or demyelinating/dysmyelinating diseases of the CNS)
Healthy Volunteer
Healthy patients with NO inflammatory and/or demyelinating/dysmyelinating diseases of the CN
结局指标
主要结局
Disease progression as assessed by clinical and MRI criteria.
时间窗: 1-2 years
1\. Sustained (i.e. \> 3 months) progression of disability as measured by =\> 0.5 CombiWISE points or 2. Development of new/clearly enlarged distinct lesions on T2WI
Definite diagnosis of MS or another disorder.
时间窗: 12 weeks
To identify MS-specific markers, biomarkers from peripheral blood and CSF will be compared between patients who fulfilled diagnostic criteria for MS versus those who were found to have alternative diagnoses.
Disease progression as assessed by clinical and MRI criteria.
时间窗: 1-2 years
1\. Sustained (i.e. \> 3 months) progression of disability as measured by =\> 0.5 CombiWISE points or 2. Development of new/clearly enlarged distinct lesions on T2WI
Definite diagnosis of MS or another disorder.
时间窗: 12 weeks
To identify MS-specific markers, biomarkers from peripheral blood and CSF will be compared between patients who fulfilled diagnostic criteria for MS versus those who were found to have alternative diagnoses.
次要结局
- Immunological biomarkers(Within 1 week of initial CSF)
- MRI measures of lesion load and CNS tissue destruction(within 1 week of first NDS visit)
- Changes in MRI measure of lesion load and CNS tissue destruction from baseline(within 1 week of follow-up visit)
- Clinical measures of disability(within 1 week of follow-up visit)
- Changes in clinical measures of disability from baseline(within 1 week of initial NDS MRI)