DiagnosE Using the Central veIn SIgn

NCT04024969 | Unknown

• 1 other identifier: 18GNS004
• Study Type: observational
• Target: 115
• Locations: 1 country
• Sites: 4

Brief Summary

There is currently no agreement on the best way to diagnose Multiple Sclerosis (MS). Frequently, people suspected of having MS have a standard MRI scan and undergo a 'lumbar puncture' (a thin needle is inserted between the bones in the lower spine). Patients often report they find it painful and it can cause unintended complications requiring hospitalisations or time off work to recover. Although the fluid taken during a lumbar puncture can show evidence of disease, this is not always the case. Doctors do not find abnormalities in everyone who has MS but some people with conditions that can mimic MS, but need very different treatment, have similar lumbar puncture abnormalities. Both of these problems can lead to misdiagnosis. A new MRI scan allows doctors to see small veins that run through damaged areas of the brain in people with MS. It has been shown that this is a specific finding to MS, seldom seen in other conditions. It is not painful and carries few or no risks. This research aims to change the way people are diagnosed with MS and reduce the number of lumbar punctures used. The investigators will recruit a large number of people from different hospitals whose doctors suspect they may have MS. They will be invited to have the new eight-minute MRI scan. After 18 months, the investigators will find out what diagnosis is eventually reached and compare this to the finding of the new scan. The investigators will then compare the accuracy, speed, costs and acceptability of the different tests needed to make a diagnosis of MS and establish if most lumbar punctures can be replaced by a slightly longer MRI scan. This research could provide the National Health Service with a scientific approach to diagnose MS which is safer, more cost effective and importantly, more acceptable to patients.

Conditions

Multiple Sclerosis

Keywords

Central Vein Sign; Translational Neuroimaging; Multiple Sclerosis

Outcome Measures

Primary Outcomes (1)

• The sensitivity of the central vein sign (CVS) on T2* MRI scan and lumbar puncture with oligoclonal band testing at diagnosing MS at the time of the patients' first presentation.

  The reference standard for both tests will be clinical diagnosis 18 months after recruitment. The sensitivity of each test will be reported separately along with 95% confidence intervals. The sensitivity of the tests will be compared using McNemar's test for paired proportions.

  18 months

Secondary Outcomes (2)

• The specificity of the central vein sign (CVS) on T2* MRI scan and lumbar puncture with oligoclonal band testing at diagnosing MS at the time of the patients' first presentation.

  18 months

• The sensitivity and specificity of the 'rule of six' proposed in Mistry et al. 2016.

  18 months

Other Outcomes (4)

• The percentage agreement between blinded raters of the CVS amongst different observers.

  18 months

• The sensitivity and specificity of combing the CVS with the results of the lumbar puncture.

  18 months

• A sensitivity analysis, allowing for variation in test performance between sites, using a mixed effects logistic regression model.

  18 months

Study Arms (1)

Clinically isolated syndrome

Those presenting for diagnositic evaluation of multiple sclerosis, not currently meeting the 2017 McDonald criteria.

Diagnostic Test: T2* MRI; Diagnostic Test: Lumbar puncture to test for presence of unmatched oligoclonal bands

Interventions

T2* MRI DIAGNOSTIC_TEST

Research T2\* weighted MRI sequence

Clinically isolated syndrome

Lumbar puncture to test for presence of unmatched oligoclonal bands DIAGNOSTIC_TEST

Current clinical standard practice

Clinically isolated syndrome

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Most participants are expected to have been evaluated by a hospital doctor (usually neurologist or ophthalmologist) at the local site and referred for diagnostic testing to the local MS team.

You may qualify if:

• Aged 18 to 65 years.
• Presentation with a typical clinically isolated syndrome (Thompson et al. 2017) for diagnostic evaluation of MS.

You may not qualify if:

• Fulfils the diagnosis of MS, as defined by the 2017 revision of McDonald diagnostic criteria (Thompson et al. 2017).
• Unwilling or unable to comply with the requirements of this protocol including the presence of any condition (physical, mental, or social) that, in the opinion of the PI, is likely to affect the participant's ability to comply with the study protocol.
• Unable to provide informed consent.
• Contraindication or inability to undergo MRI due to metal or metal implants, pregnancy, claustrophobia, pain, spasticity, or excessive movement related to tremor.

Sponsors & Collaborators

• Nottingham University Hospitals NHS Trust: lead

Study Sites (4)

Cardiff & Vale University Lhb

Cardiff, United Kingdom

RECRUITING

Barts Health Nhs Trust

London, United Kingdom

RECRUITING

Nottingham University Hospitals NHS Trust

Nottingham, United Kingdom

RECRUITING

Oxford University Hospitals Nhs Foundation Trust

Oxford, United Kingdom

RECRUITING

Related Publications (2)

• Thompson AJ, Banwell BL, Barkhof F, Carroll WM, Coetzee T, Comi G, Correale J, Fazekas F, Filippi M, Freedman MS, Fujihara K, Galetta SL, Hartung HP, Kappos L, Lublin FD, Marrie RA, Miller AE, Miller DH, Montalban X, Mowry EM, Sorensen PS, Tintore M, Traboulsee AL, Trojano M, Uitdehaag BMJ, Vukusic S, Waubant E, Weinshenker BG, Reingold SC, Cohen JA. Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. Lancet Neurol. 2018 Feb;17(2):162-173. doi: 10.1016/S1474-4422(17)30470-2. Epub 2017 Dec 21.

  PMID: 29275977 BACKGROUND

• Mistry N, Abdel-Fahim R, Samaraweera A, Mougin O, Tallantyre E, Tench C, Jaspan T, Morris P, Morgan PS, Evangelou N. Imaging central veins in brain lesions with 3-T T2*-weighted magnetic resonance imaging differentiates multiple sclerosis from microangiopathic brain lesions. Mult Scler. 2016 Sep;22(10):1289-96. doi: 10.1177/1352458515616700. Epub 2015 Dec 10.

  PMID: 26658816 BACKGROUND

MeSH Terms

Conditions

Multiple Sclerosis

Interventions

Magnetic Resonance Myelography

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)

Myelography; Neuroradiography; Neuroimaging; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis; Radiography; Magnetic Resonance Imaging; Tomography; Diagnostic Techniques, Neurological; Investigative Techniques

Study Officials

• Nikos Evangelou, MD

  Clinical Neurology, Division of Clinical Neuroscience, University of Nottingham

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Research and Innovation

CONTACT

0115 924 9924; researchsponsor@nuh.nhs.uk

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 12, 2019
• First Posted: July 18, 2019
• Study Start: November 6, 2019
• Primary Completion: May 1, 2022
• Study Completion: November 1, 2022
• Last Updated: March 4, 2020

Record last verified: 2019-07

Locations

GB (4)