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Clinical and Imaging Patterns of Neuroinflammation Diseases in China (CLUE)

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ClinicalTrials.gov Identifier: NCT04106830
Recruitment Status : Recruiting
First Posted : September 27, 2019
Last Update Posted : October 8, 2019
Sponsor:
Information provided by (Responsible Party):
Yaou Liu, Beijing Tiantan Hospital

Brief Summary:
CLUE is an prospective study to determine structural and functional changes of brain and spinal cord, as well as the inflammatory environment in patients with neuroinflammatory and demyelination disease. Subjects will receive new magnetic resonance (MR) technics including double inversion recovery (DIR) imaging diffusion kurtosis imaging (DKI), quantitative susceptibility mapping (QSM) and resting-state functional imaging and follow up for one year.

Condition or disease Intervention/treatment
NMO Spectrum Disorder MRI Multiple Sclerosis Drug: Intravenous steroid

Detailed Description:

The study is an observational study of multi model imaging to determine structural and functional changes of brain and spinal cord, as well as the inflammatory environment in patients with neuroinflammatory and demyelination disease. Brain and spinal cord involvement are common in neuroinflammatory and demyelination disease including clinical isolated syndrome (CIS), multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSDs). The pathophysiology in neuroinflammatory disease involves the intensive autoimmune inflammatory response, resulting in demyelination and neuroaxonal injury and loss. Some cerebrospinal fluid (CSF) biomarkers have been reported to indicate the pathology and reflect disease activity especially during acute stage. But they couldn't directly reflect the macroscopic and microscopic neuroaxonal change in brain and spinal cord, which seem to be important determinants of long-term severe disability in chronic neuroinflammatory disease.

Finally, new MRI techniques are the most reliable and non-invasive method to assess the structure and function of brain and spinal cord, plus to monitor disease activity in clinical practice. Double inversion recovery (DIR) imaging allows better detection of cortical and white matter lesion, which has highlighted the role in MS. Diffusion kurtosis imaging (DKI) which has been proposed to characterize the deviation of water diffusion in neural tissues from Gaussian diffusion, is promising to provide information of demyelination and subsequent inflammatory processes in brain or spinal cord. Quantitative susceptibility mapping (QSM) has enabled MRI of tissue magnetic susceptibility to advance from simple qualitative detection of hypointense blooming artifacts to precise quantitative measurement of spatial biodistributions. QSM better depicts spatial susceptibility patterns in MS lesions compared to phase-based imaging [14]. Besides, resting-state functional imaging has the potential to map the intrinsic functional brain networks and to detect early functional brain changes in neuroinflammatory disease.

This study will be a prospective cohort study of patients with neuroinflammatory and demyelination disease. Subjects will undertake MR scans at acute stage, and required follow-up visits after 1 moth, 6 months and one year. The MR scans is necessary at each visit.

This study does not limit treatment methods. Patients commonly use high-dose intravenous steroid therapy (HD-S) during acute stage. The HD-S treatment course referred to intravenous administration of 1 g of glucocorticoid daily for 3 consecutive days and continuous dose 240 mg reduction for 60mg oral administration. Immunomodulatory therapies are necessary for the remission stage. The treatment methods include: Azathioprine (start at 50 mg per day, add 50 mg per week to 2 mg/kg*d); Mycophenolate Mofetil (The initial dose was 0.25g bid, add 0.5g per week to 0.75g bid); and Rituximab (500 mg on the 1st day, the 15th day, the 30th day and the 180th day, then 500mg per year).

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Study Type : Observational [Patient Registry]
Estimated Enrollment : 1000 participants
Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration: 5 Years
Official Title: Prospective Cohort Study of Clinical and Imaging Patterns of Neuroinflammation Diseases (CLUE)
Actual Study Start Date : January 1, 2019
Estimated Primary Completion Date : December 31, 2022
Estimated Study Completion Date : December 31, 2025


Group/Cohort Intervention/treatment
NMOSD
Patients with neuromyelitis optica spectrum disorders
Drug: Intravenous steroid
This study does not limit treatment methods.patients commonly use high-dose intravenous steroid therapy (HD-S) during acute stage. The HD-S treatment course referred to intravenous administration of 1 g of glucocorticoid daily for 3 consecutive days and continuous dose 240 mg reduction for 60mg oral administration. Immunomodulatory therapies are necessary for the remission stage. The treatment methods include: Azathioprine (start at 50 mg per day, add 50 mg per week to 2 mg/kg.d); Mycophenolate Mofetil (The initial dose was 0.25g bid, add 0.5g per week to 0.75g bid); and Rituximab (500 mg on the 1st day, the 15th day, the 30th day and the 180th day, then 500mg per year).
Other Names:
  • Azathioprine
  • Mycophenolate Mofetil
  • Rituximab

Multiple sclerosis(MS)
Patients with multiple sclerosis
Drug: Intravenous steroid
This study does not limit treatment methods.patients commonly use high-dose intravenous steroid therapy (HD-S) during acute stage. The HD-S treatment course referred to intravenous administration of 1 g of glucocorticoid daily for 3 consecutive days and continuous dose 240 mg reduction for 60mg oral administration. Immunomodulatory therapies are necessary for the remission stage. The treatment methods include: Azathioprine (start at 50 mg per day, add 50 mg per week to 2 mg/kg.d); Mycophenolate Mofetil (The initial dose was 0.25g bid, add 0.5g per week to 0.75g bid); and Rituximab (500 mg on the 1st day, the 15th day, the 30th day and the 180th day, then 500mg per year).
Other Names:
  • Azathioprine
  • Mycophenolate Mofetil
  • Rituximab

Health control(HC)
Healthy people without any neuroinflammation disease



Primary Outcome Measures :
  1. The brain structural change over time between the baseline MRI and the follow-up MRIs [ Time Frame: On admission to the hospital on day 1, on discharge 180 days later and on follow up 360 days later ]
    To describe changes of lesions, grey matter and white matter in patients with neuroinflammatory and demyelination disease measured by DIR and QSM. The primary endpoint is the change over time between the baseline MRI and the follow-up MRIs, of the lesions and brain volumes.

  2. The spinal cord change over time between the baseline MRI and the follow-up MRIs. [ Time Frame: On admission to the hospital on day 1, on discharge 180 days later and on follow up 360 days later ]
    To describe changes of lesions and integrity of fiber bundle in spinal cord in neuroinflammatory and demyelination disease patients measured by DKI. The primary endpoint is the change over time between the baseline MRI and the follow-up MRIs, of structural change in spinal cord.

  3. The functional change over time between the baseline MRI and the follow-up MRIs. [ Time Frame: On admission to the hospital on day 1, on discharge 180 days later and on follow up 360 days later ]
    To describe brain functional changes in patients with neuroinflammatory and demyelination disease measured by resting-state functional imaging. The primary endpoint is the functional change over time between the baseline MRI and the follow-up MRIs


Secondary Outcome Measures :
  1. Change from Baseline Expanded Disability Status Scale (EDSS)/ Functional Systems (FS) [ Time Frame: On admission to the hospital on day 1, on discharge 180 days later and on follow up 360 days later ]
    admission to the hospital on day 1, on discharge 180 days later and on follow up 360 days later.] The Kurtzke Expanded Disability Status Scale (EDSS) was developed to measure the disability status of subjects with multiple sclerosis. It allows an objective quantification of the level of functioning that could be widely and reproducibly used by researchers and health care providers. The EDSS provides a total score on a scale that ranges from 0 to 10. The first levels 1.0 to 4.5 refer to people with a high degree of ambulatory ability and the subsequent levels 5.0 to 9.5 refer to the loss of ambulatory ability. The range of main categories include (0) = normal neurologic exam; to (5) = ambulatory without aid or rest for 200 meters; disability severe enough to impair full daily activities; to (10) = death due to Multiple sclerosis (MS). In addition, it also provides eight subscale measurements called Functional System (FS) scores.

  2. Timed 25-foot Walk [ Time Frame: On admission to the hospital on day 1, on discharge 180 days later and on follow up 360 days later ]
    Timed 25-foot walking trials will be assessed on admission to the hospital on day 1, on discharge 180 days later and on follow up 360 days later. The Timed 25-Foot Walk test is a quantitative measure of lower extremity function. If required, the subject may use an appropriate assistive device to walk as quickly as he/she can from one end to the other end of a clearly marked, unobstructed, 25-foot course. Timing will begin when any part of the subject's foot crosses the tape. Timing will end when any part of the subject's foot crosses the finish line (identified by a taped mark on the floor). Time will be recorded in seconds. The task is immediately administered again (a maximum five-minute rest period is allowed between trials) by having the subject walk back the same distance. The average of the two values will be recorded.

  3. Mean change in visual acuity as assessed by Sloan 2.5% low contrast visual acuity chart. [ Time Frame: On admission to the hospital on day 1, on discharge 180 days later and on follow up 360 days later ]

    admission to the hospital on day 1, on discharge 180 days later and on follow up 360 days later.] Low Contrast Visual Acuity: Low-contrast Sloan letter charts are readily available and provide a practical, quantitative, and standardized assessment of visual function. Each chart consists of rows of black letters (decreasing in size from top to bottom) on a white background.

    For this trial, 2.5% low contrast visual acuity will be measured on days 1 and 5 during the steroid phase and completion after the plasma exchange phase. Charts will be read at a 2.5-meter distance by trained examiners in the hospital room with constant lighting.




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Ages Eligible for Study:   16 Years to 80 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
To reflect the daily practices, this study includes all patients with neuroinflammatory and demyelination disease at the beginning of the study.
Criteria

Inclusion Criteria:

  • 18-60
  • Diagnosis of neuroinflammatory and demyelination disease
  • Availability of demographic and clinical data at the time disease onset
  • Informed written consent obtained from the patient, and/or patient's parent(s), and/or legal representative. Assent, if old enough to grant, will be obtained from all patients under the age of 18 years.

Exclusion Criteria:

  • Patients for whom MRI is contra-indicated
  • Patients included in an ongoing clinical trial where the product is blinded

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04106830


Contacts
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Contact: Yaou Liu, PhD +86 1059975396 yaouliu80@163.com

Locations
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China, Beijing
Beijing Tiantan Hospital Recruiting
Beijing, Beijing, China, 100053
Contact: Yaou Liu, PHD    +86 1059975396    yaouliu80@163.com   
Sponsors and Collaborators
Beijing Tiantan Hospital
Investigators
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Principal Investigator: Yaou Liu, PhD Beijing Tiantan Hospital
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Responsible Party: Yaou Liu, Professor, Beijing Tiantan Hospital
ClinicalTrials.gov Identifier: NCT04106830    
Other Study ID Numbers: KY 2019-050-02
First Posted: September 27, 2019    Key Record Dates
Last Update Posted: October 8, 2019
Last Verified: October 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Clinical and MR data can be shared.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Analytic Code
Time Frame: Within 5 years after the end of the trial.
Access Criteria: Neurologist and radiologist who submitting an application to Prof. Liu.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Multiple Sclerosis
Neuromyelitis Optica
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Myelitis, Transverse
Optic Neuritis
Optic Nerve Diseases
Cranial Nerve Diseases
Eye Diseases
Mycophenolic Acid
Azathioprine
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antibiotics, Antineoplastic
Antibiotics, Antitubercular
Antitubercular Agents
Anti-Bacterial Agents
Anti-Infective Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antimetabolites
Antimetabolites, Antineoplastic
Immunosuppressive Agents