Multimodal Imaging of MS Reveals the Smoldering Inflammation (PLAQ-MS)

To evaluate active MS plaque evolution with conventional MRI, QSM-post processing, TSPO-PET imaging and P2X7-PET imaging.

Study Overview

• Status: Recruiting
• Conditions: Multiple Sclerosis

Detailed Description

Objective: To establish the QSM-MRI-method as a part of MS-patient research protocol in TPC and to quantify the time and space dependent correlation of QSM-MRI signal and PET-imaging signal with both 11C-PK11195 and 11C-SMW139 radioligands in the brain of MS-patients with active disease, secondary progressive MS-patients and healthy controls.

Background: In MS brain the inflammatory lesions change over time from active to chronic active and finally to chronic inactive plaques. Conventional MRI-imaging is used to detect the lesions but it is not able to differentiate the plaque types. The most acute lesions with blood-brain-barrier defect can be identified using conventional MRI and gadolinium enhancing, but follow-up of the later plaque development with microglial activation at plaque edge is not possible using MRI. Furthermore, the diffuse microglial activation in the NAWM is not detectable with conventional MRI.

In previous studies it has been shown that chronic active plaques have a rim of active microglial cells around them. With QSM-MRI method it is possible to detect and quantify these iron containing active microglia cells around the chronic active plaque. Active microglial cells can also be detected with PET imaging and TSPO-binding radioligand 11C-PK11195 or P2X7 binding radioligand 11C-SMW139. The investigators expect that the microglial activation signals detected with QSM-MRI and PET are co-localized and that these methods would help to differentiate the plaque types and to evaluate the MS plaque evolution.

Study population: 10 MS-patients with acute gadolinium enhancing ≥0,5cm diameter lesion will be imaged at baseline and 4 and 18 months after that. For comparison 10 secondary progressive patients and 20 healthy controls will be imaged at baseline.

Methods: Clinical evaluation, brain QSM-MRI and PET imaging with 11C-PK11195 radiotracer will be performed at baseline, 4 months and 18 months. PET imaging with 11C-CSMW139 radiotracer will be performed at 4 months and 18 months.

For healthy controls, brain QSM-MRI, PET imaging with 11C-PK11195 radiotracer and PET imaging with 11C-SMW139 radiotracer will be performed at baseline. For 12 healthy controls a test-retest imaging with 11C-SMW139 radiotracer will be performed.

• Study Type: Observational
• Enrollment (Estimated): 40

Contacts and Locations

Study Locations

• Finland
  • Finland Proper
    • Turku, Finland Proper, Finland, 20520
      • Recruiting
      • Turku PET Centre
      • Contact: Laura Airas, MD,Professor; Phone Number: 023130000; Email: laura.airas@utu.fi

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

The study will recruit MS patients with active disease and at least 0,5 cm diameter gadolinium enhancing lesion who are followed-up at the Neurology Outpatient Clinic at the Turku University Hospital. The study will not interfere with the initiation or dosage of medication in any manner. For comparison the study will also recruit healthy subjects and secondary progressive MS-patients.

Description

Inclusion Criteria

Active MS-patients:

• Informed consent form
• At least one 0,5 cm diameter active gadolinium enhancing lesion detected lately
• Diagnosed MS-disease according to McDonald criteria

SPMS patients

• Informed consent form
• Diagnosed MS-disease according to McDonald criteria
• SPMS disease

Healthy controls:

• Informed consent form
• healthy
• age and sex matched with MS-patients in RRMS and SPMS groups

Exclusion Criteria

MS-patients:

• Patients suffering from another brain disease or other autoimmune disease 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
• Age over 70

Healthy controls:

• autoimmune disease, CNS disease or other serious disease
• Steroid treatment 4 weeks prior to the scan or other regular medication
• persons suffering from claustrophobia or panic disorder, or persons 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
• Age over 70

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Active MS patients; 10 MS patients with an active lesion of 0,5 cm diameter
Healthy controls; 20 healthy controls
SPMS patients; 10 SPMS patients

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
11C-PK11195 binding in MS patient brain	Change in microglia-activity in MS patients during 18 months as measured by [11C]PK11195 PET imaging	Baseline, 4 months 18 months
11C-SMW139 binding in MS patient brain	Change in microglia-activity in MS patients during 18 months as measured by [11C]SMW139 PET imaging	Baseline, 4 months 18 months
QSM-signal in MS patient brain	Change in microglia-activity in MS patients during 18 months as measured by QSM-MRI	Baseline, 4 months 18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
11C-PK11195 binding in healthy control brain	Change in microglia-activity in healthy controls during 18 months as measured by PET imaging and [11C]PK11195	Baseline
11C-SMW139 binding in healthy control brain	Change in microglia-activity in healthy controls during 18 months as measured by PET imaging [11C]SMW139	Baseline
QSM-signal in healthy control brain	Change in microglia-activity in healthy controls during 18 months as measured by QSM-MRI	Baseline
MRI metrics	To evaluate lesion load of the white matter MS plaques	Baseline, 4 months, 18 months
EDSS	Expanded Disability Status Scale. The scale ranges from 0 to 10 in 0.5 unit increments that represent higher levels of disability.	Baseline, 4 months, 18 months
MSFC	Multiple Sclerosis Composite Score which consists of three assessments of walking speed, processing speed and finger dexterity. The scores are combined to provide a Z-score. Lower scores represent greater abnormality.	Baseline, 4 months, 18 months
Fatigue severity scale	Fatigue Severity Scale is a self-reported, 9-item fatigue scale. Participants rate all 9 items on a 7-point Likert scale (1-2-3-4-5-6-7) depending on how appropriate they felt the statement applied to them over the preceding week. The total score is calculated by adding up the answer from each item and divide by 9. Lower scores indicate better outcomes. Maximum score is 7.	Baseline, 4 months, 18 months
Modified Fatigue Impact Scale	The Modified Fatigue Impact Scale is a self-report survey that contains 21 items. Each item is rated 0-4. Higher scores indicate a greater impact of fatigue on a person's activities.	Baseline, 4 months, 18 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): February 27, 2019
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: August 5, 2019
• First Submitted That Met QC Criteria: October 14, 2019
• First Posted (Actual): October 15, 2019

Study Record Updates

• Last Update Posted (Actual): April 10, 2024
• Last Update Submitted That Met QC Criteria: April 9, 2024
• Last Verified: April 1, 2024

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; Inflammation
• Other Study ID Numbers: PLAQ-MS

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