Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

To Study the Pathophysiological Features of Multiple Sclerosis

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: NCT04242056
Recruitment Status : Not yet recruiting
First Posted : January 27, 2020
Last Update Posted : January 27, 2020
Sponsor:
Information provided by (Responsible Party):
Hsu, Jung-Lung, MD, Chang Gung Memorial Hospital

Brief Summary:
Multiple sclerosis (MS) is the most common chronic inflammatory disease of the central nervous system1, whose demyelination is the pathological hallmark. MS is characterized by neuroinflammation, demyelination, axonal damage, and neurodegeneration2. The demyelination state in brain and the clinical course are difficult to predict in the early stage of disease. Recently, several neuroimaging and fluid biomarkers had been explored in MS. Using brain amyloid positron emission tomography (PET) in active MS had showed that both the damage sites and normal appearance white matter had a lower intensity than non-active MS. The result suggests a predictive role that the intensity from amyloid PET could reflect the disease activity and link to early myelin damage. The levels of tau protein in cerebrospinal fluid (CSF) had also been showed a negative correlation with brain atrophy, which is a prognostic marker for MS. In fluid biomarkers, both neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) had been used in MS and reported correlations with disease severity, the extent of neuroinflammation and progression. In current study, investigator will enroll 38 participants with MS and evaluate their clinical severity; measure the WM lesion and disease activity by magnetic resonance imaging (MRI); myelination state and amyloid deposition by amyloid PET scan; tau deposition by state of-art tau PET scan. Investigator also measure the serum levels of NfL and GFAP as the index of axonal injury and disease activity. The relationship between disease severity, brain myelination, tau deposition and serum levels of NfL will be discuss.

Condition or disease Intervention/treatment Phase
Multiple Sclerosis Neurofilament Light Chain Glial Fibrillary Acidic Protein Drug: 18F-PM-PBB3 Phase 1 Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 38 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: To Study the Pathophysiological Features of Multiple Sclerosis: Combined Multi-modalities of Amyloid and Tau Images Associated With Serum Neurofilament Light Chain Levels
Estimated Study Start Date : February 20, 2020
Estimated Primary Completion Date : September 30, 2020
Estimated Study Completion Date : September 30, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Using image to diagnosis Multiple sclerosis (MS)
In current study, we will enroll 38 patients with MS and evaluate their clinical severity; measure the WM lesion and disease activity by magnetic resonance imaging (MRI); myelination state and amyloid deposition by amyloid PET scan; tau deposition by state of-art tau PET scan
Drug: 18F-PM-PBB3

18F-PM-PBB3 brain PET studies will be conducted for 38 subjects. Dynamic PET/MRI studies will be collected by PET/MRI scanner for 100 minutes (4×15 s, 8×30 s, 960 s, 2×180 s, 8300 s, 3×600 s). Volumes of interest (VOIs) will be delineated from corresponding MR images by manual including bilateral frontal, parietal, mesial temporal, lateral temporal, hippocampal, occipital, anterior cingulate, posterior cingulate, cerebellum areas, and genu region of white matter. The DVRs will be computed from Logan graphic analysis by using cerebellum as reference input.

SUVR of every cortical VOI to the gray matter of cerebellum will be calculated from nine 10-min dynamic image sets.





Primary Outcome Measures :
  1. Correlation between hyperintensity lesions in FLAIR MRI and demyelination in amyloid PET image [ Time Frame: 3 years ]
    Investigator would be able to find the topographical correlation between hyperintensity lesions in FLAIR MRI and hypointensity lesions in amyloid PET, measurement by overlapping volume (ml) and overlapping ratio (%)


Secondary Outcome Measures :
  1. Correlation between clinical parameters (EDSS) and hyperintensity lesions in FLAIR MRI and hyperintensity region of tau PET image light chain and GFAP levels. [ Time Frame: 3 years ]
    Investigator would be able to find the EDSS correlation between whole brain hyperintensity lesions in FLAIR MRI (ml) and hyperintensity regions of tau PETwe will take this advantage to perform the study and explore the relationship between serum neruofilament light chain and GFAP levels.

  2. Correlation between clinical parameters (EDSS) and serum NfL levels [ Time Frame: 3 years ]
    Investigator would be able to find the EDSS correlation between EDSS and serum NfL levels



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   20 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age between 20-75 years old
  2. Multiple Sclerosis patients

Exclusion Criteria:

  1. Implantation of metal devices including cardiac pacemaker, intravascular metal devices.
  2. Major systemic diseases including coronary arterial disease, heart failure, uremia, hepatic failure, prominent strokes, acute myocardial infarction, poorly controlled diabetes, previous severe head injury, intracranial operation, hypoxia, sepsis or severe infectious diseases.
  3. Major psychiatric disorders, drug or alcohol abuse and major depression
  4. Pregnant women or breast- feeding women.
  5. Patients in whom MRI was contraindicated or patient had claustrophobia.
  6. History of severe allergic or anaphylactic reactions particularly to the tested drugs.
  7. History of positive test for human immunodeficiency virus (HIV).
  8. Indication of impaired liver function as shown by an abnormal liver function profile at screening (eg. repeated values of aspartate aminotransferase [AST] and alanine aminotransferase [ALT] ≧ 3X the upper limit of normal values).
Layout table for additonal information
Responsible Party: Hsu, Jung-Lung, MD, Associate Professor, Chang Gung Memorial Hospital
ClinicalTrials.gov Identifier: NCT04242056    
Other Study ID Numbers: 201802146A0
First Posted: January 27, 2020    Key Record Dates
Last Update Posted: January 27, 2020
Last Verified: January 2020

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Multiple Sclerosis
Sclerosis
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases