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Comprehensive Multimodal Analysis of Neuroimmunological Diseases of the Central Nervous System

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00794352
Recruitment Status : Recruiting
First Posted : November 20, 2008
Last Update Posted : October 26, 2020
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) )

Tracking Information
First Submitted Date November 19, 2008
First Posted Date November 20, 2008
Last Update Posted Date October 26, 2020
Actual Study Start Date October 1, 2008
Primary Completion Date Not Provided
Current Primary Outcome Measures
 (submitted: February 5, 2020)
  • 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.
  • 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 greater than or equal to 0.5 CombiWISE (Kosa,Ghazali et al. 2016) points or2. Development of new /clearly enlarged distinct lesions on T2WI
Original Primary Outcome Measures Not Provided
Change History
Current Secondary Outcome Measures
 (submitted: January 30, 2016)
  • MRI measures of lesion load and CNS tissue destruction [ Time Frame: 12 weeks ]
  • Immunological biomarkers [ Time Frame: 12 weeks ]
  • Changes in clinical measures of disability from baseline [ Time Frame: 1 year ]
  • Clinical measures of disability [ Time Frame: 12 weeks ]
  • Changes in MRI measure of lesion load and CNS tissue destruction from baseline [ Time Frame: 1 year ]
Original Secondary Outcome Measures Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Comprehensive Multimodal Analysis of Neuroimmunological Diseases of the Central Nervous System
Official Title Comprehensive Multimodal Analysis of Neuroimmunological Diseases of the CNS
Brief 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). 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

All study participants will return for a followup visit 1 year after the initial evaluation visit. 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 physiological (and often beneficial) responses of the human immune system to CNS injury. The long-term objective of the study is to acquire knowledge that would allow us to therapeutically inhibit the pathogenic mechanisms and enhance repair mechanisms in immune-mediated CNS diseases, thereby minimizing the extent of CNS tissue damage and promoting recovery.

The protocol also serves as a screening tool for NDU 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.

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 and biomarkers and to obtain normative data for development of new clinical scales and smartphone apps.

Design: We will collect, in a standardized manner, 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 immunemediated

processes are expected to play a pathophysiological role.

For the patient cohort, a comprehensive initial evaluation will be performed to establish a definitive diagnosis or confirm diagnosis and subtype of multiple sclerosis (MS) as a pre-requisite for enrollment into NDU clinical trials, but also to collect consistent multimodal research data. Additional diagnostic tests, tailored to individual patients, may be performed if required for the diagnostic process. The protocol stipulates a mandatory follow-up visit for all adult patients inclusive of clinical, functional and MRI examinations. Depending on the specific diagnosis, treatment decisions 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 is not compromised. Patients age 12-17 may also be 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 volunteer cohort will provide sex and age-matched (to adult patients) normative values.

Additionally, we will also enroll patients from whom only biological samples collected by outside clinicians will be processed. This will be done to provide non-standard assays to help with diagnostic and therapeutic decisions as a part of extraordinary clinical care.

Outcome Measures: Clinical, MRI and immunological measures will be the outcome measures. However, no pre-defined research questions will be addressed other than to establish the diagnosis, determine the level of disease activity, and monitor the natural history.

Study Type Observational
Study Design Observational Model: Case-Control
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Not Provided
Sampling Method Non-Probability Sample
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.
Condition
  • Central Nervous System Disease
  • Multiple Sclerosis
Intervention Not Provided
Study Groups/Cohorts
  • Healthy Volunteer
    Healthy patients with NO inflammatory and/or demyelinating/dysmyelinating diseases of theCN
  • Patient Cohort
    Patients who present with CNS white matter injury (including inflammatory and/or demyelinating/dysmyelinating diseases of the CNS)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Recruiting
Estimated Enrollment
 (submitted: February 20, 2020)
1200
Original Enrollment
 (submitted: November 19, 2008)
500
Study Completion Date Not Provided
Primary Completion Date Not Provided
Eligibility Criteria
  • PATIENT INCLUSION CRITERIA (for participation in the whole protocol):

    1. Presentation with a clinical syndrome consistent with immune-mediated CNS disorder and/or
    2. Neuroimaging evidence of inflammatory and/or demyelinating/ dysmyelinating CNS disease
    3. At least 12 years old at the time of enrollment
    4. 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, able to give assent with consent given by their parent or legal guardian
    5. Able to undergo the required procedures for diagnostic work-up, including lumbar puncture MRI and clinical/functional evalautions.

HEALTHY VOLUNTEER INCLUSION CRITERIA:

  1. At least 18 years old at the time of enrollment
  2. Vital signs are found within normal range at the time of the screening visit
  3. Able to give informed consent
  4. Able to undergo related research procedures, such as blood draw, lumbar puncture or lymphocytapheresis for collection of peripheral blood mononuclear cells (PBMC) samples

PATIENT INCLUSION CRITERIA for processing of collected biological samples:

  1. Presentation with a clinical syndrome consistent with immune-mediated CNS disorder and/or
  2. Neuroimaging evidence of inflammatory and/or demyelinating/ dysmyelinating CNS disease
  3. Ability to obtain either direct or surrogate informed consent for sample processing and storage

PATIENT EXCLUSION CRITERIA (for participation in the whole protocol):

  1. Significant medical condition that would make participation in diagnostic and research part of evaluation impossible or risky
  2. Medical contraindications for MRI (ie- 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)
  3. Unable to provide informed consent
  4. Unwilling to consent for collection of biological samples or their cryopreservation

HEALTHY VOLUNTEER EXCLUSION CRITERIA:

  1. Systemic inflammatory disorder or inflammatory or non-inflammatory nurological diseases.
  2. Previous or current history of alcohol and substance abuse
  3. 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)
  4. Medical contraindication for lumbar puncture
  5. Psychological contraindications for MRI (i.e. claustrophobia). This will be assessed at the time the medical history is collected.
  6. Pregnancy or current breastfeeding
  7. Any contraindications to having study procedures done<TAB>
  8. 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:

  1. Because this sub study collects no personal identifiable information (PII), there are no inclusion/exclusion criteria.
  2. 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.
Sex/Gender
Sexes Eligible for Study: All
Ages 12 Years to 99 Years   (Child, Adult, Older Adult)
Accepts Healthy Volunteers Yes
Contacts
Contact: Tiffany C Hauser (301) 496-7183 tiffany.hauser@nih.gov
Contact: Bibiana Bielekova, M.D. (240) 669-2724 bielekovab@mail.nih.gov
Listed Location Countries United States
Removed Location Countries  
 
Administrative Information
NCT Number NCT00794352
Other Study ID Numbers 090032
09-I-0032
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement Not Provided
Responsible Party National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) )
Study Sponsor National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators Not Provided
Investigators
Principal Investigator: Bibiana Bielekova, M.D. National Institute of Allergy and Infectious Diseases (NIAID)
PRS Account National Institutes of Health Clinical Center (CC)
Verification Date February 18, 2020