Investigating the Glymphatic System in Clinically Isolated Syndrome

A Pilot Study to Investigate Glymphatic System Alterations in Vivo in Patients With Clinically Isolated Syndrome, Using Magnetic Resonance Imaging

This study is trying to see if problems with the glymphatic system are linked to inflammation and disease progression in people with Clinically Isolated Syndrome, which might lead to Multiple Sclerosis.

Quick facts

• Study type: Observational
• Enrollment: 30 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University of Exeter (Academic / other)
• Locations: 2 sites (Exeter and 1 other locations)
• Trial ID: NCT06274671 on ClinicalTrials.gov

What this trial studies

This observational study aims to explore the role of the glymphatic system in Clinically Isolated Syndrome (CIS), a condition that may precede Multiple Sclerosis (MS). Participants will undergo a detailed neurological examination and provide blood and urine samples for analysis. They will also receive an MRI scan to assess potential alterations in the glymphatic system. The study seeks to determine if dysfunction in this system contributes to inflammation and disease progression in MS patients.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and over with a diagnosis of Clinically Isolated Syndrome or Multiple Sclerosis at first presentation.

Not a fit: Patients who have taken corticosteroids, IVIg, or undergone plasma exchange within the last 30 days may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide insights into new mechanisms of disease in CIS and potentially lead to novel therapeutic approaches for MS.

How similar studies have performed: While the glymphatic system has been studied in other neurological conditions, this specific approach in Clinically Isolated Syndrome is novel and has not been extensively tested.

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

Where this trial is running

Exeter and 1 other locations

• Royal Devon University Healthcare NHS Foundation Trust — Exeter, United Kingdom (Recruiting)
• University of Exeter — Exeter, United Kingdom (Not_yet_recruiting)

Study contacts

• Principal investigator: Edoardo R de Natale, MD — University of Exeter
• Study coordinator: Edoardo R de Natale, MD

Conditions Clinically Isolated Syndrome; Multiple Sclerosis; Glymphatic System; Neuroimaging