Sphingosine-1 Phosphate -Receptor Targeting and Microglial Activation

Multiple Sclerosis Clinical Trial

— FINGOPET  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02139696
• Other study ID #: FINGOPET
• Status: Completed
• Start date: September 2013
• Est. completion date: October 2016

Study information

• Verified date: May 2018
• Source: Turku University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: October 2016
• Est. primary completion date: January 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 58 Years

Eligibility

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.

Related Conditions & MeSH terms

• Multiple Sclerosis
• Sclerosis

Intervention

Radiation:
• PET and MRI
Patients will be imaged using PET and MRI at baseline, and twice during treatment

Locations

Country	Name	City	State
Finland	Turku University Hospital	Turku

Sponsors (1)

Lead Sponsor	Collaborator
Turku University Hospital

Country where clinical trial is conducted

Finland, 

References & Publications (1)

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 ¹¹C-PK11195. J Nucl Med. 2014 Jun;55(6):939-44. doi: 10.2967/jnumed.113.131698. Epub 2014 Apr 7. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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