Comprehensive Multimodal Analysis of Neuroimmunological Diseases of the Central Nervous System

Brief Summary

Official Title: “Comprehensive Multimodal Analysis of 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 between the ages of 18 and 70. 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.

  • Study Type: Observational
  • Study Design: Time Perspective: Prospective

Detailed Clinical Trial 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.

Study Population: Patients with evidence of immune-mediated CNS injury will be enrolled. In addition, healthy volunteers will be included as controls for immunological and neuroimaging biomarkers and clinical measures.

Design: We will collect, in a standardized manner, multimodal data (clinical/functional, neuroimaging and molecular/immunological data) during the diagnostic work-up of untreated 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 initial evaluation will be performed in order to establish a definitive diagnosis or confirm diagnosis and subtype of multiple sclerosis (MS) as a pre-requisite for enrollment into ongoing clinical trials, but also to collect consistent multimodal research data. This evaluation will include a standardized clinical exam, functional tests quantifying clinical disability, MRI and other neuroimaging modalities, CSF and serological studies, and lymphapheresis. Additional diagnostic tests, tailored to individual patients, may be performed if required for the diagnostic process.

The protocol stipulates a one-year mandatory follow-up for all patients inclusive of clinical and MRI imaging, as well as repetition of any additional imaging or functional testing performed during the initial evaluation. 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 in order to ensure patient safety is not compromised.

The volunteer cohort will provide sex and age-matched normative values for the immunological and imaging parameters.

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.

Outcome Measures for this Clinical Trial

Primary Measures

  • Diagnostic Study – Definite diagnosis of MS or another disorder. Follow-Up Study – Disease progession as assessed by clinical and MRI criteria.

Secondary Measures

  • Clinical measures of disability (EDSS, NRS, MSFC): MRI measures of lesions and CNS tissue destruction (T2LL, T1LL and calculated black hole fraction, measures of atrophy); and immunological biomarkers.

Criteria for Participation in this Clinical Trial

  • 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. 18-75 years of age

    4. Able to give informed consent

    5. Able to undergo complex diagnostic work-up, including lumbar puncture and MRI imaging

    6. Able to undergo related research procedures, such as lymphocytapheresis for collection of peripheral blood mononuclear cells (PBMC) samples

    HEALTHY VOLUNTEER INCLUSION CRITERIA:

    1. Age between 18 and 75

    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 disorder or central nervous system diseases of any kind or other related risk factors

    2. Previous 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. Psychological contraindications for MRI (i.e. claustrophobia). This will be assessed at the time the medical history is collected.

    5. Pregnancy or current breastfeeding

    6. Unable to provide informed consent

    7. Any contraindications to having study procedures done< TAB>

    8. History of auditory disorder (i.e. hearing impairment, known impaired acoustic reflex, tinnitus)

    Gender Eligibility for this Clinical Trial: Both

    Minimum Age for this Clinical Trial: 12 Years

    Maximum Age for this Clinical Trial: 75 Years

    Are Healthy Volunteers Accepted for this Clinical Trial: Accepts Healthy Volunteers

    Clinical Trial Investigator Information

    • Lead Sponsor
      • National Institute of Neurological Disorders and Stroke (NINDS)
    • Overall Official(s)
      • Bibiana Bielekova, M.D., Principal Investigator, National Institute of Neurological Disorders and Stroke (NINDS)
    • Overall Contact(s)
      • Jenifer E Dwyer, (301) 435-5096, jdwyer@cc.nih.gov

    References

    Andrews HE, Nichols PP, Bates D, Turnbull DM. Mitochondrial dysfunction plays a key role in progressive axonal loss in Multiple Sclerosis. Med Hypotheses. 2005;64(4):669-77.

    Arnett HA, Wang Y, Matsushima GK, Suzuki K, Ting JP. Functional genomic analysis of remyelination reveals importance of inflammation in oligodendrocyte regeneration. J Neurosci. 2003 Oct 29;23(30):9824-32.

    Astier AL, Meiffren G, Freeman S, Hafler DA. Alterations in CD46-mediated Tr1 regulatory T cells in patients with multiple sclerosis. J Clin Invest. 2006 Dec;116(12):3252-7. Epub 2006 Nov 9.

    Source

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    The URL of this page is:
    http://clinicaltrialsfeeds.org/clinical-trials/show/NCT00794352