Effect of Teriflunomide Treatment on Microglial Activation in an MS Patient Cohort at Risk of Progression

Study Overview
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Brief Summary
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To evaluate the effect of teriflunomide treatment on microglial activation in late stage multiple sclerosis.

Detailed Description
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In Multiple Sclerosis (MS), plaques in the white and grey matter of the brain represent the best known pathological changes of the disease, but a significant inflammation process has also been detected outside these plaques in connection with the disease. This extensive, diffuse inflammatory process correlates with the progression of the disease, measured by EDSS score (Expanded Disability Status Scale status) and reduction in patients' cognitive level. According to neuropathological research, the diffuse inflammatory process outside the plaques is connected with powerful activation of microglia, oxidative stress, and deficiencies in mitochondrial activity. The activation of microglial cells can be measured in vivo in patients using positron-emission tomography (PET) scanning and so-called TSPO radioligands, such as the 11C-PK11195 radioligand. 11C-PK11195 radioligand binds to TSPO molecules, which manifest on the surface of activated, but not un-activated, microglia. Teriflunomide treatment is expected to slow down the process of increasing microglial activation. TSPO-PET imaging allows in vivo follow-up of the pathogenic process associated with the gradual MS disease evolution, and allows to evaluate whether teriflunomide treatment has an effect on disease progression-related pathology.

Official Title
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Targeting SPMS: Effect of Teriflunomide Treatment on Microglial Activation in an MS Patient Cohort at Risk of Progression. A [11C]PK11195 Brain PET Study

Conditions
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Multiple Sclerosis

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signing the consent form Having used teriflunomide treatment for at least 6 months 40-55 years of age at the time of signing the research consent form MS diagnosis in accordance with either the Poser or McDonald criteria EDSS 2-6.5 Clear lesion load in brain MRI (> 9 T2 lesion) Exclusion Criteria: Patients suffering from another brain disease of in addition to multiple sclerosis Steroid treatment 4 weeks prior to the scan Significant pathology in the MRI scan other than MS-related lesions Patients suffering from claustrophobia or panic disorder, or patients who have exhibited hypersensitivity of PET markers (practical obstacle to the scan) Exposure to experimental radioactivity in the last 12 months such that the dosimetry threshold would be exceeded due to participation in the study Severe hepatic impairment Pregnant women, or women of childbearing potential who are not using reliable contraception during treatment with teriflunomide and thereafter as long as its plasma levels are above 0.02 mg/l.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Teriflunomide group<br>20 MS patients who are using teriflunomide medication under the supervision of their treating neurologist. | |
| No disease modifying treatment<br>10 MS-patients who do not use any regular disease modifying MS treatment of their own volition | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of 11C-PK11195-radioligand binding using PET | Change in microglia-activity in late RRMS patients on teriflunomide treatment during one-year interval as measured by PET imaging and [11C]PK11195 radioligand. | 0 to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MRI metrics | To evaluate lesion load of the white matter MS plaques | 0, 12 months, 24 months, 36 months | 
| EDSS | Expanded Disability Status Scale | 0, 12 months, 24 months, 36 months | 
| BICAMS | Brief International Cognitive Assessment for MS | 0, 36 months |