Clinically Isolated SyndromeNCT06274671
Glymphatic MRI in Clinically Isolated Syndrome
An observational study of Clinically Isolated Syndrome, run by University of Exeter at 2 sites in United Kingdom.
Trial summary
The brain possesses a system to get rid of unwanted substances, named Glymphatic System (GS). When this system is faulty, these accumulate, there is local inflammation, and progressive death of the cells. This occurs in neurological diseases including Parkinson's, or Alzheimer's. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Clinically Isolated Syndrome
- What is being tested?
- Magnetic Resonance Imaging
- How many people
- 30 participants
- Where
- 2 sitesUnited Kingdom
- Study dates
- 1 May 2024to 31 Dec 2026
- 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 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Group 1: Patients with a diagnosis of Clinically Isolated Syndrome Group 2: Healthy controls
Who may be able to join
- Male or female, aged 18 or over
- Suitable physically and psychologically to undertake the assessments, as judged by the Investigator
- Have voluntarily provided informed consent and have signed an ICF indicating that the purpose of the study has been explained and are willing and able to adhere to the study procedures described in the ICF.
- (For CIS group): A diagnosis of CIS or MS at first presentation
- Subjects must not have taken corticosteroids or IVIg or plasma-exchange within the 30 days prior to consent
- Adequate vision and hearing to perform the study procedures
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- Medically healthy with no clinically significant findings on physical examination, laboratory profiles, vital signs at screening (with the exception of the signs of the condition under investigation)
- Women of child-bearing potential must practice a medically acceptable method of birth control. Acceptable methods include oral contraceptive, contraceptive patch, long-acting injectable contraceptive, or double-barrier method (condom or intrauterine device with spermicide).
- If on immunomodulatory medication, patients must have started it at least 30 days from screening and should not change their medication dose for the duration of the study.
Who cannot join
- Have a diagnosis of clinically definite Multiple Sclerosis according to the 2017 McDonald's Criteria (Thompson et al., 2018)
- Have a CIS limited to the spinal cord (transverse myelitis)
- Present psychiatric disorders or severe cognitive deficit
- Past or present history of drug or alcohol abuse
- Are pregnant or breastfeeding, if females of childbearing potential
- Have any other medical, neurological, or psychiatric condition or clinically significant laboratory abnormality excluding CIS which, in the opinion of the Investigator, might preclude participation
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- Are taking benzodiazepines on a regular basis or are unable to suspend intake of benzodiazepines
- Have received any investigational product within a time-period equal to five half-lives of the product, if known, or minimum of 60 days before consent
- Are unable to lie down for MRI scanning
- Have any finding on the brain MRI that would compromise subject safety or the scientific integrity of the study
- Have implants, such as implanted cardiac pacemakers or defibrillators, insulin pumps, cochlear implants, metallic ocular foreign body, implanted neural stimulators, aneurysm clips, or other medical implants that have not been deemed safe for MRI
- Have a history of claustrophobia
- Have any other contraindication to MRI scanning
- Have a relapse occurred after consent but before the MRI scan
- It is preferable the following laboratory tests are part of the subject's medical history for differential diagnosis of clinically isolated syndrome (CIS): erythrocyte sedimentation rate (ESR), antinuclear antibody (ANA), complement (C3, C4) and anticardiolipin IgG - IgM
Trial locations and contacts
2 sites in 1 country.
United Kingdom2 sites
Royal Devon University Healthcare NHS Foundation Trust
Exeter
University of Exeter
Exeter
About this study
Official title: A Pilot Study to Investigate Glymphatic System Alterations in Vivo in Patients With Clinically Isolated Syndrome, Using Magnetic Resonance Imaging
The brain possesses a system to get rid of unwanted substances, named Glymphatic System (GS). When this system is faulty, these accumulate, there is local inflammation, and progressive death of the cells. This occurs in neurological diseases including Parkinson's, or Alzheimer's. Inflammation and progressive death of the cells are also present in another neurological disorder, named Multiple Sclerosis (MS).
Doctors think that GS dysfunction plays a role in MS too. In this research therefore, the aim is to study whether it drives inflammation, and disease progression in MS patients.
Read more
The researchers have developed a new way to find signs of alteration of the GS using a scan named Magnetic Resonance Imaging (MRI) and will use it in a pilot study on patients with a condition named Clinically Isolated Syndrome (CIS), which often represents the very beginning of MS. It would therefore be demonstrated that the GS is a new mechanism of disease in CIS, which may associate with the symptoms, or the alterations in the levels of some substances in the blood suggestive of brain cells damage.
Should this study be successful, this would provide preliminary evidence to perform a larger research study to assess if GS dysfunction drives the progression of MS.
Read the detailed description
This is a cross-sectional case-control study on patients with a diagnosis of Clinically Isolated Syndrome (CIS) and a group of age- and gender-matched healthy controls.
In this study all participants will undergo two visits. In the first visit, all participants will sign the informed consent form and perform a detailed neurological examination, with administration of a few questionnaires for assessment of symptoms related to CIS/Multiple Sclerosis. Participants will also donate a sample of blood for safety analysis, analysis of biomarkers related to CIS and the glymphatic system, as well as for storage in a biobank. Participants will donate a sample of urine for urinalysis and pregnancy test in females of childbearing potential.
In the second visit, all participants will visit the Mireille Gillings Neuroimaging Centre of the University of Exeter for an MRI scan, that will last about 60 minutes.
- Conditions
- Clinically Isolated Syndrome
- Being tested
- Magnetic Resonance Imaging
- Keywords
- Clinically Isolated Syndrome, Multiple Sclerosis, Glymphatic System, Neuroimaging
- Medical subject headings
- Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Magnetic Resonance ImagingOther
A Magnetic Resonance Imaging (duration: about 60 minutes) with research sequences for the visualization of alterations of the glymphatic system.
| Study group | Role | What they receive |
|---|---|---|
| Clinically Isolated Syndrome | Patients with a diagnosis of Clinically Isolated Syndrome Receives: Other: Magnetic Resonance Imaging | |
| Healthy Controls | Age- and gender-matched healthy controls. Receives: Other: Magnetic Resonance Imaging |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine that patients with CIS display alterations of the glymphatic system visible in vivo by Structural MRI
Difference between CIS and HV in the number of perivascular spaces
Measured: Through study completion, an average of 7 days
To determine that patients with CIS display alterations of the glymphatic system visible in vivo by microstructural MRI
Difference between CIS and HV in estimation of intraparenchymal water transport
Measured: Through study completion, an average of 7 days
To determine that patients with CIS display alterations of the glymphatic system visible in vivo by diffusion-weighted MRI
Difference between CIS and HV in the calculation of the ALPS-index
Measured: Through study completion, an average of 7 days
To determine that patients with CIS display alterations of the glymphatic system visible in vivo by perfusion-MRI
Difference between CIS and HV in estimation of choroid plexus perfusion
Measured: Through study completion, an average of 7 days
To determine that patients with CIS display alterations of the glymphatic system visible in vivo by ALS-MRI
Difference between CIS and HV in estimation of Cerebrospinal Fluid (CSF) flow
Measured: Through study completion, an average of 7 days
Secondary outcomes (9)
To correlate in vivo measures of altered glymphatic system with MRI measures of structural integrity in CIS
Quantification in CIS of structural volumetric and thickness
Measured: Through study completion, an average of 7 days
To correlate in vivo measures of altered glymphatic system with MRI measures of disease activity in CIS
Quantification in CIS of total lesion load
Measured: Through study completion, an average of 7 days
To correlate in vivo measures of altered glymphatic system with MRI measures of enlarged Wirchow-Robin spaces in CIS
Quantification in CIS of perivascular spaces
Measured: Through study completion, an average of 7 days
To correlate in vivo measures of altered glymphatic system with MRI measures of microstructural altertions in CIS
Quantification in CIS of free water, a measure of extracellular space
Measured: Through study completion, an average of 7 days
To correlate in vivo measures of altered glymphatic system with MRI measures of brain perfusion in CIS
Quantification in CIS of water transport and regional perfusion.
Measured: Through study completion, an average of 7 days
To correlate in vivo measures of altered glymphatic system in CIS with clinical measures of disease severity
Correlation between MRI measures and EDSS score in CIS patients.
Measured: Through study completion, an average of 7 days
To correlate in vivo measures of altered glymphatic system in CIS with fluid biomarkers of axonal injury in CIS
Correlation between MRI measures and fluid biomarkers for neuroaxonal integrity (calculated with the quantification of Neurofilament Light Chain (NfL)
Measured: Through study completion, an average of 7 days
To correlate in vivo measures of altered glymphatic system in CIS with fluid biomarkers of astrocytis integrity in CIS
Correlation between MRI measures and fluid biomarkers for astrocytic activation (calculated with the quantification of Glial Fibrillary Acid Protein (GFAP)
Measured: Through study completion, an average of 7 days
To correlate in vivo measures of altered glymphatic system in CIS with fluid biomarkers of glymphatic activity in CIS
Correlation between MRI measures and fluid biomarkers for glymphatic transport damage (calculated with the quantification of Aquaporin 4 (AQP4) and of Neuronal-Specific Enolase (NSE)
Measured: Through study completion, an average of 7 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Feb 2024
- Study start1 May 2024
- Primary completion31 Dec 2026 (estimated)
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Clinically Isolated SyndromeStudies of the same condition, open and under way.
- 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
- Case-control
- Time perspective
- Cross-sectional
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Exeter
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Edoardo R de Natale, MD, Principal investigator, University of Exeter
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06274671
- Sponsor's protocol ID
- 23-24-09
- Status last verified
- May 2026
- First submitted
- 31 Jan 2024
- Last updated
- 8 May 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study to Investigate Glymphatic System Alterations in Vivo in Patients With Clinically Isolated Syndrome, Using Magnetic Resonance Imaging
- ClinicalTrials.gov ID
- NCT06274671
- Acronym / sponsor ID
- 23-24-09
- Conditions
- Clinically Isolated Syndrome
- Keywords
- Clinically Isolated Syndrome, Multiple Sclerosis, Glymphatic System, Neuroimaging
- Study type
- Observational
- Recruitment status
- Active, not recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- University of ExeterUniversity, hospital or other
- Study start
- 1 May 2024 (actual)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 23 Feb 2024 (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.
The brain possesses a system to get rid of unwanted substances, named Glymphatic System (GS). When this system is faulty, these accumulate, there is local inflammation, and progressive death of the cells. This occurs in neurological diseases including Parkinson's, or Alzheimer's. Inflammation and progressive death of the cells are also present in another neurological disorder, named Multiple Sclerosis (MS).
Doctors think that GS dysfunction plays a role in MS too. In this research therefore, the aim is to study whether it drives inflammation, and disease progression in MS patients.
The researchers have developed a new way to find signs of alteration of the GS using a scan named Magnetic Resonance Imaging (MRI) and will use it in a pilot study on patients with a condition named Clinically Isolated Syndrome (CIS), which often represents the very beginning of MS. It would therefore be demonstrated that the GS is a new mechanism of disease in CIS, which may associate with the symptoms, or the alterations in the levels of some substances in the blood suggestive of brain cells damage.
Should this study be successful, this would provide preliminary evidence to perform a larger research study to assess if GS dysfunction drives the progression of MS.
Detailed description
This is a cross-sectional case-control study on patients with a diagnosis of Clinically Isolated Syndrome (CIS) and a group of age- and gender-matched healthy controls.
In this study all participants will undergo two visits. In the first visit, all participants will sign the informed consent form and perform a detailed neurological examination, with administration of a few questionnaires for assessment of symptoms related to CIS/Multiple Sclerosis. Participants will also donate a sample of blood for safety analysis, analysis of biomarkers related to CIS and the glymphatic system, as well as for storage in a biobank. Participants will donate a sample of urine for urinalysis and pregnancy test in females of childbearing potential.
In the second visit, all participants will visit the Mireille Gillings Neuroimaging Centre of the University of Exeter for an MRI scan, that will last about 60 minutes.
Study design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Clinically Isolated Syndrome | – | Other: Magnetic Resonance ImagingPatients with a diagnosis of Clinically Isolated Syndrome |
| Healthy Controls | – | Other: Magnetic Resonance ImagingAge- and gender-matched healthy controls. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Group 1: Patients with a diagnosis of Clinically Isolated Syndrome Group 2: Healthy controls
Key inclusion criteria (9 listed)
- Male or female, aged 18 or over
- Suitable physically and psychologically to undertake the assessments, as judged by the Investigator
- Have voluntarily provided informed consent and have signed an ICF indicating that the purpose of the study has been explained and are willing and able to adhere to the study procedures described in the ICF.
- (For CIS group): A diagnosis of CIS or MS at first presentation
- Subjects must not have taken corticosteroids or IVIg or plasma-exchange within the 30 days prior to consent
Key exclusion criteria (15 listed)
- Have a diagnosis of clinically definite Multiple Sclerosis according to the 2017 McDonald's Criteria (Thompson et al., 2018)
- Have a CIS limited to the spinal cord (transverse myelitis)
- Present psychiatric disorders or severe cognitive deficit
- Past or present history of drug or alcohol abuse
- Are pregnant or breastfeeding, if females of childbearing potential
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 |
|---|---|---|
| Magnetic Resonance ImagingA Magnetic Resonance Imaging (duration: about 60 minutes) with research sequences for the visualization of alterations of the glymphatic system. | Other | Clinically Isolated Syndrome, Healthy Controls |
Primary outcome
To determine that patients with CIS display alterations of the glymphatic system visible in vivo by Structural MRI
Time frame: Through study completion, an average of 7 days
Difference between CIS and HV in the number of perivascular spaces
To determine that patients with CIS display alterations of the glymphatic system visible in vivo by microstructural MRI
Time frame: Through study completion, an average of 7 days
Difference between CIS and HV in estimation of intraparenchymal water transport
To determine that patients with CIS display alterations of the glymphatic system visible in vivo by diffusion-weighted MRI
Time frame: Through study completion, an average of 7 days
Difference between CIS and HV in the calculation of the ALPS-index
To determine that patients with CIS display alterations of the glymphatic system visible in vivo by perfusion-MRI
Time frame: Through study completion, an average of 7 days
Difference between CIS and HV in estimation of choroid plexus perfusion
To determine that patients with CIS display alterations of the glymphatic system visible in vivo by ALS-MRI
Time frame: Through study completion, an average of 7 days
Difference between CIS and HV in estimation of Cerebrospinal Fluid (CSF) flow
9 secondary outcomes
To correlate in vivo measures of altered glymphatic system with MRI measures of structural integrity in CIS
Time frame: Through study completion, an average of 7 days
To correlate in vivo measures of altered glymphatic system with MRI measures of disease activity in CIS
Time frame: Through study completion, an average of 7 days
To correlate in vivo measures of altered glymphatic system with MRI measures of enlarged Wirchow-Robin spaces in CIS
Time frame: Through study completion, an average of 7 days
To correlate in vivo measures of altered glymphatic system with MRI measures of microstructural altertions in CIS
Time frame: Through study completion, an average of 7 days
To correlate in vivo measures of altered glymphatic system with MRI measures of brain perfusion in CIS
Time frame: Through study completion, an average of 7 days
To correlate in vivo measures of altered glymphatic system in CIS with clinical measures of disease severity
Time frame: Through study completion, an average of 7 days
To correlate in vivo measures of altered glymphatic system in CIS with fluid biomarkers of axonal injury in CIS
Time frame: Through study completion, an average of 7 days
To correlate in vivo measures of altered glymphatic system in CIS with fluid biomarkers of astrocytis integrity in CIS
Time frame: Through study completion, an average of 7 days
To correlate in vivo measures of altered glymphatic system in CIS with fluid biomarkers of glymphatic activity in CIS
Time frame: Through study completion, an average of 7 days
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 8 May 2026.
- Individual participant dataSharing planned: No
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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.
Edoardo R de Natale, MD principal investigator
University of Exeter
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Clinically Isolated Syndrome, run by University of Exeter at 2 sites in United Kingdom.
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 9 inclusion and 15 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 8 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United Kingdom. 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?
To determine that patients with CIS display alterations of the glymphatic system visible in vivo by Structural MRI (time frame: Through study completion, an average of 7 days). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 8 May 2026.