An observational study in Central Nervous System Disease and Multiple Sclerosis, sponsored by National Institute of Allergy and Infectious Diseases (NIAID). Recruiting at 1 site in United States. Open to participants aged 1 Month to 99 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-11-10.
Sponsored by National Institute of Allergy and Infectious Diseases (NIAID) · Observational
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:
Patients with symptoms of immune-related CNS damage may be offered the opportunity to participate in additional followup tests with NIH researchers.
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
Patients with evidence, or suspicion of immune-mediated CNS injury. Healthy volunteers (HV) are included as controls for immunological and imaging biomarkers and to obtain normative data for development of new clinical scales and smartphone apps.
DESIGN
Collection of multimodal data (standardized clinical/functional, neuroimaging and molecular/immunological data) during the diagnostic work-up of patients with varied disorders of the CNS in which immune-mediated processes are expected to play a pathophysiological role.
For the patient cohort, a comprehensive evaluation establishes a definitive diagnosis or confirms diagnosis and subtype of multiple sclerosis (MS) as a pre-requisite for enrollment into NDS clinical trials. Depending on the diagnosis and clinical/research needs, patients may be offered follow-up visits. The number and timing of follow-up visits will vary. Most people will have
visits every 6-12 months. The maximum frequency of the follow-up visits and research samples to be collected is specified to ensure patient safety. Patients aged 12-17 years are included in the patient cohort to establish a definitive diagnosis, or to provide non-standard assays to help with diagnostic and therapeutic decisions as part of extraordinary clinical care.
The HV provide sex and age-matched (to adult patients) normative values.
A "telemedicine" patient sub-cohort enrolls patients who cannot (for any reason, but usually advanced disability) come to NIH for in-person evaluation. From these telemedicine patients, we will estimate neurological disability by Combinatorial MRI Scale (COMRIS) models derived from outside brain and spinal cord MRIs, and by NeuFun-TS smartphone application. Telemedicine patients will contribute capillary blood from at-home collection kits for research applications. Telemedicine patients with confirmed diagnosis of neuroimmunological disorder may be referred to NIAID Centralized Sequencing protocol (17-I-0122) for genetic testing.
A "sample processing only" patient subcohort enrolls patients from whom only biological samples and data collected by outside clinicians are processed and evaluated to provide non-standard assays.
A collaboration was in place until December 26, 2022, with the U.S. Food \& Drug Administration (FDA) that included collection of clinical and normative data for diagnostic and research purposes. The FDA Principal Investigator Dr. Wenyu Sun will assist with the needs of the protocol by performing minimal protocol related procedures. Such procedures are discussed throughout Study Design and Methods.
OUTCOME MEASURES
Clinical, MRI, and immunological outcomes are outlined in this section. However, no pre-defined research questions will be addressed other than to establish the diagnosis, determine the level of disability, provide prognostic information, and monitor the natural history.
3,264 studies on the registry are indexed under Multiple Sclerosis; 659 are open to participants now.
This study's planned enrollment of 2,400 is above the median of 100 across 970 observational studies indexed under Multiple Sclerosis.
Browse Multiple Sclerosis studies →National Institute of Allergy and Infectious Diseases (NIAID) is the lead sponsor of 2,446 studies on the registry; 179 are open to participants now.
Of its 405 completed or terminated interventional studies of FDA-regulated products, 302 (75%) have results posted.
Compared within Multiple Sclerosis, this study's primary condition as ClinicalTrials.gg classifies it; the registry's first condition term is Central Nervous System Diseases. The counts are of registry records indexed under each term, refreshed daily. How we classify →
The criteria were revised on the registry on Nov 10, 2026. See what changed
Patients with evidence, or suspicion of immune-mediated CNS injury will be enrolled. In addition, healthy volunteers will be included as controls for immunological and imaging biomarkers and to obtain normative data for development of new clinical scales and smartphone apps.
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 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
PATIENT EXCLUSION CRITERIA (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 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 (e.g. 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 (e.g. 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 (e.g. 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.
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Healthy patients with NO inflammatory and/or demyelinating/dysmyelinating diseases of the CN
Patients who present with CNS white matter injury (including inflammatory and/or demyelinating/dysmyelinating diseases of the CNS)
Disease progression as assessed by clinical and MRI criteria.
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
Time frame: 1-2 years
Definite diagnosis of MS or another disorder.
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.
Time frame: 12 weeks
MRI measures of lesion load and CNS tissue destruction
for initial evaluation
Time frame: within 1 week of first NDS visit
Immunological biomarkers
for initial evaluation
Time frame: Within 1 week of initial CSF
Clinical measures of disability
for longitudinal evaluation
Time frame: within 1 week of follow-up visit
Changes in MRI measure of lesion load and CNS tissue destruction from baseline
for longitudinal evaluation
Time frame: within 1 week of follow-up visit
Changes in clinical measures of disability from baseline
for initial evaluation
Time frame: within 1 week of initial NDS MRI
Plan to share: No
Started Oct 2008 (actual).
How these figures are worked out, and which studies are left out of them.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
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