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

Active, not recruiting

• Conditions: Multiple Sclerosis

• Registration Number: NCT03368677
• Lead Sponsor: Turku University Hospital

Brief Summary

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

Detailed Description

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.

Study Timeline

• Study First Submitted: 2017-10-02
• Study Start: 2017-12-01
• Study First Submitted QC: 2017-12-08
• Study First Posted: 2017-12-11
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-11
• Last Update Posted: 2025-04-13
• Primary Completion: 2027-06
• Study Completion: 2027-12

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 26

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.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
EDSS	0, 12 months, 24 months, 36 months	Expanded Disability Status Scale
BICAMS	0, 36 months	Brief International Cognitive Assessment for MS
MRI metrics	0, 12 months, 24 months, 36 months	To evaluate lesion load of the white matter MS plaques

Trial Locations

Locations (1)

Turku PET Centre; 🇫🇮 Turku, Finland Proper, Finland