Multiple SclerosisCLADPETNCT04239820
Effect of Cladribine Treatment on Microglial Activation in the CNS
An observational study of Multiple Sclerosis, run by Turku University Hospital at 1 site in Finland.
Trial summary
To evaluate the effect of cladribine treatment on microglial activation with conventional MRI, QSM-post processing and TSPO-PET imaging in late stage relapsing remitting multiple sclerosis patients. Read more about this study
- Who is it for?
- Ages 45 to 55 years
- Conditions the study is for
- Multiple Sclerosis
- What is being tested?
- Imaging
- Type of treatment
- Surgery or procedure
- How many people
- 15 participants
- Where
- 1 siteFinland
- Study dates
- 10 Jan 2020to Dec 2025
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 45 to 55 years
- All sexes
- No healthy volunteers
- Adult
Study population: The research will recruit MS patients who are initiating cladribine treatment and are followed-up at the Neurology Outpatient Clinic at the areas of the Hospital District of Southwest Finland, Helsinki and Uusimaa Hospital District, Pirkanmaa Hospital District and Satakunta Hospital District. 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 initiating cladribine medication will be offered the option to participate in this imaging study.
Who may be able to join
- Signing the informed consent form
- Cladribine treatment is planned and indicated and is according to label
- 45-55 years of age at the time of signing the research informed consent form
- RRMS diagnosis in accordance with McDonald 2017 criteria
Who cannot join
- Patients with other neurodegenerative disease than MS
- Abnormal lymphocyte counts
- Patients with human immunodeficiency virus (HIV).
- Patients with active chronic infection (tuberculosis or hepatitis).
- Patients with active malignancy.
- Patients with moderate or severe renal impairment (creatinine clearance <60 mL/min)
Show all 16Show fewer
- Patients that are pregnant or breast-feeding
- 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.
- Patients with previous alemtuzumab administration
- Patients with less than 6 months since previous administration of ocrelizumab or rituximab (or with abnormal B-cell counts)
- Patients with less than 1 month since previous administration of other disease modifying therapy
Trial locations and contacts
1 site in 1 country.
About this study
To evaluate the effect of cladribine treatment on microglial activation with conventional MRI, QSM-post processing and TSPO-PET imaging in late stage relapsing remitting multiple sclerosis patients.
Read the detailed description
Objective: To evaluate with multimodal magnetic resonance (MR) imaging and TSPO-PET imaging whether cladribine treatment has an effect on disease progression-related pathology in late stage relapsing remitting multiple sclerosis (RRMS) patients.
Background: 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. 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 18 kilodalton translocator protein (TSPO) -radioligands. TSPO-radioligands, such as the 11C-PK11195 radioligand, bind to TSPO molecules, which manifest in activated, but not un-activated, microglia.
Cladribine is an immune cell depleting treatment for RRMS. Our hypothesis is that monitoring the treatment of MS could be carried out using TSPO-PET and Quantitative susceptibility mapping (QSM)-MRI scanning, and these multimodal imaging methods could be used to assess the impact of the cladribine medication on the disease process leading to progression and disability by measuring the activation status of microglial cells.
An age-matched historical control group of 10 untreated RRMS patients that have been previously imaged at a 12-18 months interval will be used for comparison.
Study population: 15 late stage RRMS-patients Methods: Clinical evaluation, brain QSM-MRI and PET imaging with 11C-PK11195 radiotracer will be performed at baseline and 18 months.
- Conditions
- Multiple Sclerosis
- Being tested
- Imaging
- Medical subject headings
- Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ImagingRadiation
MRI and TSPO-PET imaging at baseline and 18 months after baseline
| Study group | Role | What they receive |
|---|---|---|
| RRMS patients initiating cladribine | Patients will be imaged using PET and MRI at baseline prior the cladribine treatment initiation and 18 months after baseline Receives: Radiation: Imaging |
What is being measured
The primary outcome is the main question the study is designed to answer.
11C-PK11195 binding in MS patient brain
Change in microglia-activity in MS patients during 18 months as measured by 11C-PK11195 PET imaging
Measured: baseline, 18 months
Secondary outcomes (6)
MRI metrics
To evaluate lesion load of the white matter MS plaques
Measured: Baseline, 18 months
Expanded Disability Status Scale
Expanded Disability Status Scale. The scale ranges from 0 to 10 in 0.5 unit increments that represent higher levels of disability.
Measured: Baseline, 18 months
Multiple Sclerosis Composite Score
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.
Measured: Baseline, 18 months
Blood biomarkers
Change in serum neurofilament light (NfL) and glial fibrillary acid protein (GFAP)
Measured: Baseline, 18 months
11C-PK11195 difference in RRMS and historical healthy controls
Difference in microglia-activity between RRMS and historical healthy controls during 18 months as measured by PET imaging and 11C-PK11195
Measured: Baseline, 18 months
QSM-signal in MS patient brain
Change in microglia-activity in MS patients during 18 months as measured by QSM-MRI
Measured: baseline, 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jan 2020
- Study start10 Jan 2020
- Primary completion15 Feb 2024
- Study completionDec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Multiple SclerosisStudies of the same condition, open and under way.
- More trials run by Turku University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Turku University Hospital
- Sponsor type
- Other government
- Responsible party
- Sponsor
- Investigators
- Laura Airas, Professor, Principal investigator, Turku University Hospital, division of clinical neurosciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04239820
- Sponsor's protocol ID
- 142/2019
- Other IDs
- 2019-001960-31, 2019
- Acronym
- CLADPET
- Status last verified
- Jan 2025
- First submitted
- 21 Jan 2020
- Last updated
- 15 Jan 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Rajalehto O, Matilainen M, Lehto J, Honkonen E, Koivumaki M, Wahlroos S, Rajander J, Misin O, Luoma A, Laaksonen S, Vuorimaa A, Sucksdorff M, Saraste M, Airas L. Impact of Oral Cladribine on TSPO-PET-Measurable Immune Cell Activation in Multiple Sclerosis. Neurol Ther. 2026 Sep 30. doi: 10.1007/s40120-026-01044-5. Online ahead of print.
PubMed 42814343Sjoros T, Saraste M, Matilainen M, Nylund M, Koivumaki M, Kuhle J, Leppert D, Airas L. Serum glial fibrillary acid protein associates with TSPO-expressing lesions in multiple sclerosis brain. Ther Adv Neurol Disord. 2025 Jul 28;18:17562864251352998. doi: 10.1177/17562864251352998. eCollection 2025.
PubMed 40756531
Study at a glance
From the registry record, last updated by the sponsor on 15 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Cladribine Treatment on Microglial Activation in the CNS
- ClinicalTrials.gov ID
- NCT04239820
- Acronym / sponsor ID
- CLADPET / 142/2019
- Conditions
- Multiple Sclerosis
- Study type
- Observational
- Recruitment status
- Active, not recruiting
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Turku University HospitalOther government
- Study start
- 10 Jan 2020 (actual)
- Primary completion
- 15 Feb 2024 (actual)
- Study completion
- Dec 2025 (estimated)
- First posted
- 27 Jan 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To evaluate the effect of cladribine treatment on microglial activation with conventional MRI, QSM-post processing and TSPO-PET imaging in late stage relapsing remitting multiple sclerosis patients.
Detailed description
Objective: To evaluate with multimodal magnetic resonance (MR) imaging and TSPO-PET imaging whether cladribine treatment has an effect on disease progression-related pathology in late stage relapsing remitting multiple sclerosis (RRMS) patients.
Background: 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. 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 18 kilodalton translocator protein (TSPO) -radioligands. TSPO-radioligands, such as the 11C-PK11195 radioligand, bind to TSPO molecules, which manifest in activated, but not un-activated, microglia.
Cladribine is an immune cell depleting treatment for RRMS. Our hypothesis is that monitoring the treatment of MS could be carried out using TSPO-PET and Quantitative susceptibility mapping (QSM)-MRI scanning, and these multimodal imaging methods could be used to assess the impact of the cladribine medication on the disease process leading to progression and disability by measuring the activation status of microglial cells.
An age-matched historical control group of 10 untreated RRMS patients that have been previously imaged at a 12-18 months interval will be used for comparison.
Study population: 15 late stage RRMS-patients Methods: Clinical evaluation, brain QSM-MRI and PET imaging with 11C-PK11195 radiotracer will be performed at baseline and 18 months.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| RRMS patients initiating cladribine | – | Radiation: ImagingPatients will be imaged using PET and MRI at baseline prior the cladribine treatment initiation and 18 months after baseline |
Who may qualify
- Ages
- 45 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
- Study population
- The research will recruit MS patients who are initiating cladribine treatment and are followed-up at the Neurology Outpatient Clinic at the areas of the Hospital District of Southwest Finland, Helsinki and Uusimaa Hospital District, Pirkanmaa Hospital District and Satakunta Hospital District. 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 initiating cladribine medication will be offered the option to participate in this imaging study.
Key inclusion criteria (4 listed)
- Signing the informed consent form
- Cladribine treatment is planned and indicated and is according to label
- 45-55 years of age at the time of signing the research informed consent form
- RRMS diagnosis in accordance with McDonald 2017 criteria
Key exclusion criteria (16 listed)
- Patients with other neurodegenerative disease than MS
- Abnormal lymphocyte counts
- Patients with human immunodeficiency virus (HIV).
- Patients with active chronic infection (tuberculosis or hepatitis).
- Patients with active malignancy.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ImagingMRI and TSPO-PET imaging at baseline and 18 months after baseline | Radiation | RRMS patients initiating cladribine |
Primary outcome
11C-PK11195 binding in MS patient brain
Time frame: baseline, 18 months
Change in microglia-activity in MS patients during 18 months as measured by 11C-PK11195 PET imaging
6 secondary outcomes
MRI metrics
Time frame: Baseline, 18 months
Expanded Disability Status Scale
Time frame: Baseline, 18 months
Multiple Sclerosis Composite Score
Time frame: Baseline, 18 months
Blood biomarkers
Time frame: Baseline, 18 months
11C-PK11195 difference in RRMS and historical healthy controls
Time frame: Baseline, 18 months
QSM-signal in MS patient brain
Time frame: baseline, 18 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jan 2025.
- Derived from this study: PubMed 42814343Rajalehto O, Matilainen M, Lehto J, Honkonen E, Koivumaki M, Wahlroos S, Rajander J, Misin O, Luoma A, Laaksonen S, Vuorimaa A, Sucksdorff M, Saraste M, Airas L. Impact of Oral Cladribine on TSPO-PET-Measurable Immune Cell Activation in Multiple Sclerosis. Neurol Ther. 2026 Sep 30. doi: 10.1007/s40120-026-01044-5. Online ahead of print.
- Derived from this study: PubMed 40756531Sjoros T, Saraste M, Matilainen M, Nylund M, Koivumaki M, Kuhle J, Leppert D, Airas L. Serum glial fibrillary acid protein associates with TSPO-expressing lesions in multiple sclerosis brain. Ther Adv Neurol Disord. 2025 Jul 28;18:17562864251352998. doi: 10.1177/17562864251352998. eCollection 2025.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Laura Airas, Professor principal investigator
Turku University Hospital, division of clinical neurosciences
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Multiple Sclerosis, run by Turku University Hospital at 1 site in Finland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 15 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Finland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
11C-PK11195 binding in MS patient brain (time frame: baseline, 18 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04239820, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jan 2025.