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

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

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

Study Overview

• Status: Active, not recruiting
• Conditions: 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 Type: Observational
• Enrollment (Actual): 26

Contacts and Locations

Study Locations

• Finland
  • Finland Proper
    • Turku, Finland Proper, Finland, 20520
      • Turku PET Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 55 years (Adult)
• Accepts Healthy Volunteers: No

• 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.

Description

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 Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Teriflunomide group; 20 MS patients who are using teriflunomide medication under the supervision of their treating neurologist.
No disease modifying treatment; 10 MS-patients who do not use any regular disease modifying MS treatment of their own volition

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Turku University Hospital
• Investigators: Principal Investigator: Laura Airas, MD,Professor, Turku University Hospital, division of clinical neurosciences

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2017
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: October 2, 2017
• First Submitted That Met QC Criteria: December 8, 2017
• First Posted (Actual): December 11, 2017

Study Record Updates

• Last Update Posted (Actual): April 13, 2025
• Last Update Submitted That Met QC Criteria: April 11, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Autoimmune Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Multiple Sclerosis
• Other Study ID Numbers: TERIPET

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No