Sphingosine-1 Phosphate -Receptor Targeting and Microglial Activation (FINGOPET)

Does Targeting of Sphingosine-1 Phosphate Receptors Reduce Microglial Activation in Multiple Sclerosis? A [11C]PK11195 Brain PET Study

To evaluate the usability of positron emission tomography imaging as a novel outcome measure in multiple sclerosis studies

Study Overview

• Status: Completed
• Conditions: Multiple Sclerosis
• Intervention / Treatment: Radiation: PET and MRI

Detailed Description

Background and Rationale

In multiple sclerosis (MS), significant pathology correlating to disease progression, to expanded disability status scale (EDSS) and to cognitive decline, takes place outside the plaque areas, i.e. in areas of normal appearing white matter and gray matter. Neuropathological studies suggest that mechanisms involved in this widespread pathology include activation of microglial cells, oxidative stress and deficiency in mitochondrial functions. Activated microglia can be detected in vivo with a translocator protein (TSPO), expressed in activated, but not resting microglia) binding radioligands and positron emission tomography (PET). 11Carbon-PK11195 radioligand is one such radioligand. Importantly, the possible effect of MS therapies on microglial activity can be evaluated in patients in vivo with PET-imaging performed before and after the treatment.

• Study Type: Observational
• Enrollment (Actual): 10

Contacts and Locations

Study Locations

• Finland
  • Turku, Finland, 20520
    • Turku University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 58 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

10 patients with multiple sclerosis who will be initiated on fingolimod in the neurology outpatient clinic of the Turku University hospital in Turku, Finland.

Description

Inclusion Criteria:

Having signed the informed consent of the investigator-initiated PET study

• Age 18 - 58 years at the time of informed consent.
• MS according to Poser or McDonald criteria
• EDSS score from 0.0 to 6.5.
• Moderate to heavy lesion load ( >9 T2 lesions) in MRI

Exclusion Criteria:

• - Patients with other neurodegenerative disease than MS
• Disease modifying therapy (DMT) within 4 weeks of imaging
• Corticosteroid treatment within 4 weeks of imaging
• Patients with significant abnormal findings other than MS in the screening MRI.
• Patients with claustrophobia, or a history of moderate to severe anxiety disorder or panic attacks (which could potentially lead to preterm termination of the imaging)
• Contraindication to PET scan investigations
• Exposure to experimental radiation in the past 12 months such that radiodosimetry limits would be exceeded by participating in this study.
• Intolerance to previous PET scans; i.e. previous hypersensitivity reactions to any PET ligand or imaging agent or failure to participate in and comply with previous PET scans.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
MS patients initiating fingolimod; Patients will be imaged using PET and MRI at baseline, and twice during treatment.	Radiation: PET and MRI; Patients will be imaged using PET and MRI at baseline, and twice during treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of 11C-PK11195-radioligand binding using PET	Patients will be switched to fingolimod from first-line therapies as per indication and as part of their normal treatment regimen, and those who will consent to participate in this investigator-initiated PET study, will be imaged at baseline (pre-treatment phase) and after 6-8 weeks and 24 weeks of treatment. Purpose is to compare the binding of the radioligand between these three time points.	0 to 24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MRI metrics	To evaluate the total lesion load of the white matter MS plaques with MRI; baseline vs. 6-8 weeks vs. 24 weeks of Gilenya treatment	0, 6-8 wk, 24 wk

Collaborators and Investigators

• Sponsor: Turku University Hospital
• Investigators: Principal Investigator: Laura Airas, MD, PhD, Turku University Hospital

Publications and helpful links

General Publications

• Rissanen E, Tuisku J, Rokka J, Paavilainen T, Parkkola R, Rinne JO, Airas L. In Vivo Detection of Diffuse Inflammation in Secondary Progressive Multiple Sclerosis Using PET Imaging and the Radioligand (1)(1)C-PK11195. J Nucl Med. 2014 Jun;55(6):939-44. doi: 10.2967/jnumed.113.131698. Epub 2014 Apr 7.

Study record dates

Study Major Dates

• Study Start: September 1, 2013
• Primary Completion (Actual): January 1, 2015
• Study Completion (Actual): October 1, 2016

Study Registration Dates

• First Submitted: May 8, 2014
• First Submitted That Met QC Criteria: May 13, 2014
• First Posted (Estimate): May 15, 2014

Study Record Updates

• Last Update Posted (Actual): May 11, 2018
• Last Update Submitted That Met QC Criteria: May 4, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

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

Plan for Individual participant data (IPD)

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