Glymphatic MRI in Clinically Isolated Syndrome

NCT06274671 | Active Not Recruiting

• 1 other identifier: 23-24-09
• Study Type: observational
• Target: 30
• Locations: 1 country
• Sites: 2

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.

Conditions

Clinically Isolated Syndrome

Keywords

Clinically Isolated Syndrome; Multiple Sclerosis; Glymphatic System; Neuroimaging

Outcome Measures

Primary Outcomes (5)

• 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

  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

  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

  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

  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

  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

  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

  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

  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

  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

  Through study completion, an average of 7 days

Study Arms (2)

Clinically Isolated Syndrome

Patients with a diagnosis of Clinically Isolated Syndrome

Other: Magnetic Resonance Imaging

Healthy Controls

Age- and gender-matched healthy controls.

Other: Magnetic Resonance Imaging

Interventions

Magnetic Resonance Imaging OTHER

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

Clinically Isolated Syndrome; Healthy Controls

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Group 1: Patients with a diagnosis of Clinically Isolated Syndrome Group 2: Healthy controls

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• University of Exeter: lead

Study Sites (2)

Royal Devon University Healthcare NHS Foundation Trust

Exeter, United Kingdom

Location

University of Exeter

Exeter, United Kingdom

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood samples will be analyzed for biomarkers related to Clinically Isolated Syndrome and the function of the glymphatic system, and will be stored with consent for future analysis related to CIS/glymphatic system research.

MeSH Terms

Conditions

Multiple Sclerosis

Interventions

Magnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques

Study Officials

• Edoardo R de Natale, MD

  University of Exeter

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 31, 2024
• First Posted: February 23, 2024
• Study Start: May 1, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: May 8, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

GB (2)