Glymphatic MRI in Clinically Isolated Syndrome

NCT ID: NCT06274671

Last Updated: 2025-10-07

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 30 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2024-05-01
• Study Completion Date: 2025-12-31

Brief 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. 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.

Conditions

Clinically Isolated Syndrome

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: CROSS_SECTIONAL

Study Groups

Clinically Isolated Syndrome

Patients with a diagnosis of Clinically Isolated Syndrome

Magnetic Resonance Imaging

Intervention Type: OTHER

A Magnetic Resonance Imaging (duration: about 60 minutes) with research sequences for the visualization of alterations of the glymphatic system.

Healthy Controls

Age- and gender-matched healthy controls.

Magnetic Resonance Imaging

Intervention Type: OTHER

A Magnetic Resonance Imaging (duration: about 60 minutes) with research sequences for the visualization of alterations of the glymphatic system.

Interventions

Magnetic Resonance Imaging

A Magnetic Resonance Imaging (duration: about 60 minutes) with research sequences for the visualization of alterations of the glymphatic system.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

1. Male or female, aged 18 or over

2. Suitable physically and psychologically to undertake the assessments, as judged by the Investigator

3. 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.

4. (For CIS group): A diagnosis of CIS or MS at first presentation

5. Subjects must not have taken corticosteroids or IVIg or plasma-exchange within the 30 days prior to consent

6. Adequate vision and hearing to perform the study procedures

7. 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)

8. 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).

9. 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.

Exclusion Criteria

1. Have a diagnosis of clinically definite Multiple Sclerosis according to the 2017 McDonald's Criteria (Thompson et al., 2018)

2. Have a CIS limited to the spinal cord (transverse myelitis)

3. Present psychiatric disorders or severe cognitive deficit

4. Past or present history of drug or alcohol abuse

5. Are pregnant or breastfeeding, if females of childbearing potential

6. 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

7. Are taking benzodiazepines on a regular basis or are unable to suspend intake of benzodiazepines

8. 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

9. Are unable to lie down for MRI scanning

10. Have any finding on the brain MRI that would compromise subject safety or the scientific integrity of the study

11. 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

12. Have a history of claustrophobia

13. Have any other contraindication to MRI scanning

14. Have a relapse occurred after consent but before the MRI scan

15. 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of Exeter

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Edoardo R de Natale, MD

Role: PRINCIPAL_INVESTIGATOR

University of Exeter

Locations

University of Exeter

Exeter, Exeter, United Kingdom

Site Status: NOT_YET_RECRUITING

Royal Devon University Healthcare NHS Foundation Trust

Exeter, , United Kingdom

Site Status: RECRUITING

Countries

United Kingdom

Central Contacts

Edoardo R de Natale, MD

Role: CONTACT

e.de-natale@exeter.ac.uk

07503741242

Holly Wright

Role: CONTACT

h.wright3@exeter.ac.uk

Facility Contacts

Edoardo R de Natale, MD

Role: primary

e.de-natale@exeter.ac.uk

Samantha Smart

Role: primary

Other Identifiers

23-24-09

Identifier Type: -

Identifier Source: org_study_id