Clinical trial NCT03368677: Effect of Teriflunomide Treatment on Microglial Activation in an MS Patient Cohort at Risk of Progression
Official title: Targeting SPMS: Effect of Teriflunomide Treatment on Microglial Activation in an MS Patient Cohort at Risk of Progression. A [11C]PK11195 Brain PET Study
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Multiple Sclerosis
Lead sponsor: Turku University Hospital
Sponsor class: OTHER_GOV
First posted: 2017-12-11
Enrollment: 26
Sex: ALL
Minimum age (years): 40
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The research will recruit MS patients who are using teriflunomide treatment and are followed-up at the Neurology Outpatient Clinic at the Turku University Hospital. The study will not interfere with the initiation or dosage of the medication in any manner. The patient's treating neurologist will select the most suitable medication on the basis of the patient's clinical status, and patients using teriflunomide medication will be offered the option to participate in this imaging research.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change of 11C-PK11195-radioligand binding using PET
timeFrame: 0 to 12 months
Secondary outcomes:
measure: MRI metrics
timeFrame: 0, 12 months, 24 months, 36 months
measure: EDSS
timeFrame: 0, 12 months, 24 months, 36 months
measure: BICAMS
timeFrame: 0, 36 months
Other outcomes:
Locations:
city: Turku
country: Finland
facility: Turku PET Centre
state: Finland Proper
Study officials:
affiliation: Turku University Hospital, division of clinical neurosciences
name: Laura Airas, MD,professor
role: PRINCIPAL_INVESTIGATOR
References: