Central Nervous System DiseaseNCT00794352
Comprehensive Multimodal Analysis of Neuroimmunological Diseases of the Central Nervous System
An observational study of Central Nervous System Disease and Multiple Sclerosis, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 1 month to 99 yearsHealthy volunteers can take part
- Conditions the study is for
- Central Nervous System Disease, Multiple Sclerosis
- How many people
- 2,400 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Oct 2008to not given
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 month to 99 years
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Study population: 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.
- 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
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 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
Official title: Comprehensive Multimodal Analysis of Patients With Neuroimmunological Diseases of the CNS
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.
Read more
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.
Read the detailed description
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. Adult patients have a mandatory follow-up visit approximately 1-2 years from protocol enrollment. Depending on the diagnosis and clinical/research needs, patients may be offered additional follow-up visits. The maximum frequency of the follow-up visits and research samples to be collected is specified to ensure patient safety. Patients age 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 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.
- Conditions
- Central Nervous System Disease, Multiple Sclerosis
- Keywords
- Inflammation, Multiple Sclerosis, Neuroimmunology, Immune Disorder, Neuroimaging, Natural History, Central Nervous System Disease, Healthy Volunteers, HV
- Medical subject headings
- Central Nervous System Diseases, Multiple Sclerosis, Inflammation, Immune System Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Healthy Volunteer | Healthy patients with NO inflammatory and/or demyelinating/dysmyelinating diseases of the CN | |
| Patient Cohort | Patients who present with CNS white matter injury (including inflammatory and/or demyelinating/dysmyelinating diseases of the CNS) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Disease progression as assessed by clinical and MRI criteria.
- 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
Measured: 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.
Measured: 12 weeks
Secondary outcomes (5)
MRI measures of lesion load and CNS tissue destruction
for initial evaluation
Measured: within 1 week of first NDS visit
Immunological biomarkers
for initial evaluation
Measured: Within 1 week of initial CSF
Clinical measures of disability
for longitudinal evaluation
Measured: within 1 week of follow-up visit
Changes in MRI measure of lesion load and CNS tissue destruction from baseline
for longitudinal evaluation
Measured: within 1 week of follow-up visit
Changes in clinical measures of disability from baseline
for initial evaluation
Measured: within 1 week of initial NDS MRI
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Nov 2008 (estimated)
- Study start1 Oct 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Central Nervous System DiseaseStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 2,400 participants (estimated)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Bibiana Bielekova, M.D., Principal investigator, National Institute of Allergy and Infectious Diseases (NIAID)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00794352
- Sponsor's protocol ID
- 090032
- Other IDs
- 09-I-0032
- Status last verified
- 30 Sep 2026
- First submitted
- 19 Nov 2008
- Last updated
- 8 Oct 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Kim Y, Varosanec M, Kosa P, Bielekova B. Confounder-adjusted MRI-based predictors of multiple sclerosis disability. Front Radiol. 2022 Sep 13;2:971157. doi: 10.3389/fradi.2022.971157. eCollection 2022.
PubMed 37492673Kosa P, Masvekar R, Komori M, Phillips J, Ramesh V, Varosanec M, Sandford M, Bielekova B. Enhancing the clinical value of serum neurofilament light chain measurement. JCI Insight. 2022 Aug 8;7(15):e161415. doi: 10.1172/jci.insight.161415.
PubMed 35737460
Study at a glance
From the registry record, last updated by the sponsor on 8 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comprehensive Multimodal Analysis of Patients With Neuroimmunological Diseases of the CNS
- ClinicalTrials.gov ID
- NCT00794352
- Acronym / sponsor ID
- 090032
- Conditions
- Central Nervous System Disease, Multiple Sclerosis
- Keywords
- Inflammation, Multiple Sclerosis, Neuroimmunology, Immune Disorder, Neuroimaging, Natural History, Central Nervous System Disease, Healthy Volunteers
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 2,400 participants (estimated)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- 1 Oct 2008 (actual)
- First posted
- 20 Nov 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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. Adult patients have a mandatory follow-up visit approximately 1-2 years from protocol enrollment. Depending on the diagnosis and clinical/research needs, patients may be offered additional follow-up visits. The maximum frequency of the follow-up visits and research samples to be collected is specified to ensure patient safety. Patients age 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 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.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Healthy Volunteer | – | –Healthy patients with NO inflammatory and/or demyelinating/dysmyelinating diseases of the CN |
| Patient Cohort | – | –Patients who present with CNS white matter injury (including inflammatory and/or demyelinating/dysmyelinating diseases of the CNS) |
Who may qualify
- Ages
- 1 month to 99 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
- Study population
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Disease progression as assessed by clinical and MRI criteria.
Time frame: 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.
Time frame: 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.
5 secondary outcomes
MRI measures of lesion load and CNS tissue destruction
Time frame: within 1 week of first NDS visit
Immunological biomarkers
Time frame: Within 1 week of initial CSF
Clinical measures of disability
Time frame: within 1 week of follow-up visit
Changes in MRI measure of lesion load and CNS tissue destruction from baseline
Time frame: within 1 week of follow-up visit
Changes in clinical measures of disability from baseline
Time frame: within 1 week of initial NDS MRI
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Oct 2026.
- Derived from this study: PubMed 37492673Kim Y, Varosanec M, Kosa P, Bielekova B. Confounder-adjusted MRI-based predictors of multiple sclerosis disability. Front Radiol. 2022 Sep 13;2:971157. doi: 10.3389/fradi.2022.971157. eCollection 2022.
- Derived from this study: PubMed 35737460Kosa P, Masvekar R, Komori M, Phillips J, Ramesh V, Varosanec M, Sandford M, Bielekova B. Enhancing the clinical value of serum neurofilament light chain measurement. JCI Insight. 2022 Aug 8;7(15):e161415. doi: 10.1172/jci.insight.161415.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Bibiana Bielekova, M.D. principal investigator
National Institute of Allergy and Infectious Diseases (NIAID)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Central Nervous System Disease and Multiple Sclerosis, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 8 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Amir Moghadam Ahmadi, M.D. ((301) 761-5333, amir.moghadamahmadi@nih.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Disease progression as assessed by clinical and MRI criteria. (time frame: 1-2 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00794352, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Oct 2026.