Central Vein Sign: a Diagnostic Biomarker in Multiple Sclerosis

Running, not enrolling

Conditions studied: Multiple Sclerosis

In brief

The need for improved diagnostic methods in Multiple Sclerosis (MS) is widely recognized. Although Magnetic Resonance Imaging (MRI) is a longstanding tool for detecting MS lesions, diagnostic inaccuracies persist. Up to 20% of people diagnosed with MS (1 in 5) are later found not to have the disease. This is highly consequential, as more than two-thirds of misdiagnosed patients are unnecessarily exposed to risks from disease-modifying therapies, which in rare cases can be life-threatening. Moreover, the current standard in MS diagnosis - the McDonald criteria, which combine clinical symptoms and MRI findings - were developed from studies in people with typical clinical presentations of MS. This reduces the specificity of these criteria, rendering them uninformative for the nearly half of MS patients who present to neurologists with atypical or nonclassical symptoms. Timeliness of MS diagnosis is also key, as diagnostic delay is common in cases of relapsing-remitting MS and can carry severe and lifelong consequences. The CentrAl Vein Sign in MS (CAVS-MS) study has been designed to assess whether Central Vein Sign (CVS) criteria can help address some of these unmet diagnostic needs. It will specifically explore the role of presentation type by enrolling a mixed population of patients with typical clinical presentations (n = 200) and those with atypical presentations, including suggestive MRI findings in the absence of neurologic symptoms (n = 200) across North America.

Key facts

Study ID: NCT04495556
Run by: The Cleveland Clinic
People needed: 420
Starts: 2020-06-11
Expected to finish: 2027-01-01
Last updated by the study team: 2025-10-02

Who can join

Age: 18 and older, up to 65. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

Inclusion criteria for participants with typical presentations will include:
Age 18 to 65 inclusive
Referral to a study academic site for a clinical suspicion of MS
Onset with typical symptom onset including: acute unilateral optic neuritis, double vision due to an internuclear ophthalmoplegia or sixth nerve palsy, facial sensory loss or trigeminal neuralgia in a young adult (<40 years of age), cerebellar ataxia and nystagmus, partial myelopathy, sensory symptoms in a CNS pattern, Lhermitte's symptom, asymmetric limb weakness, urge incontinence or erectile dysfunction, or other neurological presentation considered to be typical by the site investigator.
Able to provide written informed consent to participate in the study
For participants referred for clinical suspicion of multiple sclerosis who had workup prior to referral or who are taking disease-modifying therapies for MS, digital availability of diagnostic cranial MRI with gadolinium within 3 months of initial symptoms
Onset of typical neurological symptoms within 10 years of screening.
Inclusion criteria for participants with atypical presentations will include:
Age 18 to 65 inclusive
Referral to a study academic site for a suspicion of MS
Onset with atypical onset including: bilateral optic neuritis or unilateral optic neuritis with a poor visual recovery, complete gaze palsy or fluctuating ophthalmoparesis, intractable nausea, vomiting, or hiccups, complete transverse myelopathy with bilateral motor and sensory involvement, encephalopathy, subacute cognitive decline, headache or meningismus, isolated fatigue or asthenia, constitutional symptoms, other clinical presentations considered atypical by the site investigator (examples include: vague or patchy sensory symptoms, pain, short lasting bilateral blurred vision, etc.), or absence of clinical symptoms with MRI features suggestive of MS
Able to provide written informed consent to participate in the study
For participants referred for clinical suspicion of multiple sclerosis who had workup prior to referral or who are taking disease-modifying therapies for MS, digital availability of diagnostic cranial MRI with gadolinium within 3 months of initial symptoms
Onset of atypical neurological symptoms within 10 years of screening.

You may not qualify if…

Exclusion criteria for both typical and atypical populations will include:
Contraindication to MRI studies; metal or metal implants incompatible with MRI
Inability to tolerate MRI due to claustrophobia or known excessive movement (e.g. tremor)
Contraindication to use of gadolinium containing contrast agents (allergy or renal failure)
Treatment with systemic corticosteroids in the 4 weeks preceding enrollment.

Where it is running

Cedars-Sinai Medical Center — Los Angeles, California, United States
University of Southern California — Los Angeles, California, United States
University of Colorado — Aurora, Colorado, United States
Yale University — New Haven, Connecticut, United States
Johns Hopkins University — Baltimore, Maryland, United States
Washington University in St. Louis — St Louis, Missouri, United States
Cleveland Clinic Foundation — Cleveland, Ohio, United States
University of Pennsylvania — Philadelphia, Pennsylvania, United States
The University of Texas at Austin — Austin, Texas, United States
University of Vermont — Burlington, Vermont, United States
St. Michael's Hospital of Unity Health Toronto — Toronto, Ontario, Canada

Full record on ClinicalTrials.gov

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