Accurate Diagnosis of Multiple Sclerosis Using PET/MR
Primary Purpose
Multiple Sclerosis
Status
Completed
Phase
Not Applicable
Locations
China
Study Type
Interventional
Intervention
18F-florbetapir PET+MRSI
Sponsored by

About this trial
This is an interventional diagnostic trial for Multiple Sclerosis
Eligibility Criteria
MS Patients Group:
Inclusion Criteria:
- between 18-65 years old;
- diagnosed with mild or moderate disease (EDSS score ≤ 5 points); it meets the 2017 new version of McDonald diagnostic criteria for multiple sclerosis.
- meet the diagnostic criteria of clinically isolated syndromes (CIS)
Exclusion Criteria:
- No brain surgery/no brain trauma/no history of brain disease (stroke), no other independent neurological or psychiatric history;
- No severe depression symptoms;
- No alcoholism or drug dependence (addiction);
- No other conditions that affect the smooth progress of the inspection: such as hearing impairment, comprehension impairment, poor compliance, etc.;
- No rheumatic diseases and other acute or chronic inflammations (required for hematological markers).
- No MR contrast agent allergy
Healthy Volunteers Group:
Inclusion Criteria:
- between 18-65 years old;
- able to understand the purpose of clinical research and test plan;
- In the brain MR assessment, it is judged as "normal (corresponding to age)"
Exclusion Criteria:
- Any major mental illness; history of schizophrenia or schizoaffective disorder
- Any important neurological disease, such as cerebrovascular disease, inflammation or infectious disease, demyelinating disease, neurodegenerative disease, history of epilepsy or history of physical or craniocerebral trauma or brain surgery or intracranial hematoma with permanent brain history of injury;
- Brain MR has pathological manifestations;
- Any major diseases or unstable conditions (such as unstable angina, myocardial infarction or coronary revascularization within 12 months before enrollment, heart failure, chronic renal failure, chronic liver disease, severe lung disease, blood disease, poorly controlled diabetes, chronic infections);
- Medical history of tumors (except skin or prostate cancer in situ) within 5 years before screening;
- High risk of drug allergy (such as patients with allergic asthma) or history of severe allergic reactions to allergens;
- History of alcohol or drug abuse/dependence;
- MR contraindications (such as pacemaker or nerve stimulator or metal foreign body, high fever, etc.)
Sites / Locations
- Shanghai Ruijin Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Sham Comparator
Arm Label
MS Patients Group
Healthy Volunteers Group
Arm Description
Outcomes
Primary Outcome Measures
Distribution Volume Ratio (DVR)
Dynamic parameter of 18F-florbetapir distribution for quantitatively assessing the demyelination
Change from Baseline DVR at 6 months
Change of 18F-florbetapir distribution in the demyelinated lesions after 6 months
Change from Baseline DVR at 1 year
Change of 18F-florbetapir distribution in the demyelinated lesions after 1 year
Standardized Uptake Value Ratio (SUVR)
Static parameter of 18F-florbetapir uptake for quantitatively assessing the demyelination
Change from Baseline SUVR at 6 months
Change of 18F-florbetapir uptake in the demyelinated lesions after 6 months
Change from Baseline SUVR at 1 year
Change of 18F-florbetapir uptake in the demyelinated lesions after 1 year
N-acetyl aspartate (NAA) quantification
Neuronal activity marker based on magnetic resonance spectroscopy imaging (MRSI)
Change from Baseline NAA at 6 months
Change of neuronal activity marker in the demyelinated lesions after 6 months
Change from Baseline NAA at 1 year
Change of neuronal activity marker in the demyelinated lesions after 1 year
Secondary Outcome Measures
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04521439
Brief Title
Accurate Diagnosis of Multiple Sclerosis Using PET/MR
Official Title
Hybrid PET/MR Imaging to Assess Demyelination and Axonal Injury in Multiple Sclerosis
Study Type
Interventional
2. Study Status
Record Verification Date
March 2022
Overall Recruitment Status
Completed
Study Start Date
February 1, 2020 (Actual)
Primary Completion Date
March 30, 2022 (Actual)
Study Completion Date
July 30, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ruijin Hospital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Multiple sclerosis (MS) is an immune-mediated chronic inflammatory demyelinating disease of the central nervous system. Its main feature is progressive demyelination, which ultimately leads to axon damage and neuron loss. MR is the main imaging technique in the current diagnostic criteria of MS. The conventional MR sequence recommended in this diagnostic criteria has high sensitivity for detecting demyelination and axon damage, but has poor specificity, which makes disease modification therapy (DMT) blind, and it is also difficult to accurately determine the long-term prognosis.
PET is a non-invasive molecular imaging technology that can quantitatively monitor physiological or pathological processes in vivo. 18F-labeled thioflavin derivative probe (18F-florbetapir) can bind to myelin basic protein in the white matter, providing quantitative assessment of myelin content. Our preliminary studies have confirmed that the uptake of 18F-florbetapir in MS lesions is significantly related to the myelin content measured by histological staining. Therefore, 18F-florbetapir PET may be a very effective myelin imaging technology.
Advanced MR sequence such as magnetic resonance spectroscopy (MRS) can evaluate axonal damage by analyzing neuronal activity marker N-acetyl aspartate (NAA). The new whole-brain fast 3D MRS sequence breaks through the bottleneck of low signal-to-noise ratio and spatial resolution of the current MRS sequence, and provides a reliable method for obtaining neuronal activity markers in the three-dimensional space of MS sporadic lesions in the whole brain.
Integrated PET/MR makes PET detector implant in the MR magnet, which realizes the simultaneous acquisition of PET and MR in one scan, ensuring the high consistency of the two modes. This makes it possible to simultaneously analyze PET and MRS quantitative parameters in multiple and different sizes of MS lesions, that is, to obtain two different pathological features of demyelination and neuronal damage. Separating these two pathological changes will help to more accurately and quantitatively evaluate the efficacy of DMT, program selection and prognostic judgment.
This project intends to recruit 30 MS patients between 18-65 years old, and 30 healthy volunteers with matched age and sex as normal controls. PET/MR imaging, serological examination and cerebrospinal fluid testing and scale evaluation will be performed. The aim of this project is to planned to establish a new imaging evaluation technology for accurate diagnosis and prognosis evaluation of MS.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Sclerosis
7. Study Design
Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
49 (Actual)
8. Arms, Groups, and Interventions
Arm Title
MS Patients Group
Arm Type
Experimental
Arm Title
Healthy Volunteers Group
Arm Type
Sham Comparator
Intervention Type
Diagnostic Test
Intervention Name(s)
18F-florbetapir PET+MRSI
Intervention Description
PET and MRS quantitative parameters in MS lesions are simultaneously analyzed using hybrid PET/MR for obtaining demyelination and neuronal damage information.
Primary Outcome Measure Information:
Title
Distribution Volume Ratio (DVR)
Description
Dynamic parameter of 18F-florbetapir distribution for quantitatively assessing the demyelination
Time Frame
Baseline
Title
Change from Baseline DVR at 6 months
Description
Change of 18F-florbetapir distribution in the demyelinated lesions after 6 months
Time Frame
6 months after baseline
Title
Change from Baseline DVR at 1 year
Description
Change of 18F-florbetapir distribution in the demyelinated lesions after 1 year
Time Frame
1 year after baseline
Title
Standardized Uptake Value Ratio (SUVR)
Description
Static parameter of 18F-florbetapir uptake for quantitatively assessing the demyelination
Time Frame
Baseline
Title
Change from Baseline SUVR at 6 months
Description
Change of 18F-florbetapir uptake in the demyelinated lesions after 6 months
Time Frame
6 months after baseline
Title
Change from Baseline SUVR at 1 year
Description
Change of 18F-florbetapir uptake in the demyelinated lesions after 1 year
Time Frame
1 year after baseline
Title
N-acetyl aspartate (NAA) quantification
Description
Neuronal activity marker based on magnetic resonance spectroscopy imaging (MRSI)
Time Frame
Baseline
Title
Change from Baseline NAA at 6 months
Description
Change of neuronal activity marker in the demyelinated lesions after 6 months
Time Frame
6 months after baseline
Title
Change from Baseline NAA at 1 year
Description
Change of neuronal activity marker in the demyelinated lesions after 1 year
Time Frame
1 year after baseline
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
MS Patients Group:
Inclusion Criteria:
between 18-65 years old;
diagnosed with mild or moderate disease (EDSS score ≤ 5 points); it meets the 2017 new version of McDonald diagnostic criteria for multiple sclerosis.
meet the diagnostic criteria of clinically isolated syndromes (CIS)
Exclusion Criteria:
No brain surgery/no brain trauma/no history of brain disease (stroke), no other independent neurological or psychiatric history;
No severe depression symptoms;
No alcoholism or drug dependence (addiction);
No other conditions that affect the smooth progress of the inspection: such as hearing impairment, comprehension impairment, poor compliance, etc.;
No rheumatic diseases and other acute or chronic inflammations (required for hematological markers).
No MR contrast agent allergy
Healthy Volunteers Group:
Inclusion Criteria:
between 18-65 years old;
able to understand the purpose of clinical research and test plan;
In the brain MR assessment, it is judged as "normal (corresponding to age)"
Exclusion Criteria:
Any major mental illness; history of schizophrenia or schizoaffective disorder
Any important neurological disease, such as cerebrovascular disease, inflammation or infectious disease, demyelinating disease, neurodegenerative disease, history of epilepsy or history of physical or craniocerebral trauma or brain surgery or intracranial hematoma with permanent brain history of injury;
Brain MR has pathological manifestations;
Any major diseases or unstable conditions (such as unstable angina, myocardial infarction or coronary revascularization within 12 months before enrollment, heart failure, chronic renal failure, chronic liver disease, severe lung disease, blood disease, poorly controlled diabetes, chronic infections);
Medical history of tumors (except skin or prostate cancer in situ) within 5 years before screening;
High risk of drug allergy (such as patients with allergic asthma) or history of severe allergic reactions to allergens;
History of alcohol or drug abuse/dependence;
MR contraindications (such as pacemaker or nerve stimulator or metal foreign body, high fever, etc.)
Facility Information:
Facility Name
Shanghai Ruijin Hospital
City
Shanghai
ZIP/Postal Code
200025
Country
China
12. IPD Sharing Statement
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Accurate Diagnosis of Multiple Sclerosis Using PET/MR
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