MRI for Multiple Sclerosis

(CAVS-MS Trial)

Not currently recruiting at 12 trial locations

Overseen By Meghan E Kilbane, BS

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: The Cleveland Clinic

Must not be taking: Systemic corticosteroids

Disqualifiers: Metal implants, Claustrophobia, Renal failure, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 6

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to improve the diagnosis of Multiple Sclerosis (MS), a disease where the immune system attacks the protective cover of nerves. Many people currently receive a misdiagnosis of MS, leading to unnecessary treatments. The trial will test a new method called the Central Vein Sign (CVS) to determine if it identifies MS more accurately, particularly in individuals with unusual or hard-to-spot symptoms. Those experiencing symptoms like sudden vision problems, unexplained fatigue, or unusual nerve pain may be suitable candidates for this study. As a Phase 2 trial, this research measures the effectiveness of the new diagnostic method in an initial, smaller group, offering participants a chance to contribute to improving MS diagnosis.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does mention that you cannot have been treated with systemic corticosteroids in the 4 weeks before joining. If you're on disease-modifying therapies for MS, you can still participate if you have a recent MRI available.

What prior data suggests that this diagnostic method is safe for patients with Multiple Sclerosis?

Research has shown that the Central Vein Sign (CVS) is a valuable tool for diagnosing multiple sclerosis (MS). Studies examining thousands of MS lesions have found that CVS helps doctors distinguish MS from other conditions, leading to more accurate diagnoses.

Current research is assessing CVS's effectiveness in different patients. CVS uses MRI technology, which is both common and safe. No reports have indicated problems specifically related to using CVS during an MRI.

As this method aims to improve diagnosis without involving new drugs or treatments, there are no additional risks from new medications. Overall, using the Central Vein Sign in MRIs is expected to be safe for patients. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it focuses on using the Central Vein Sign as a diagnostic biomarker for Multiple Sclerosis (MS), which could revolutionize how we detect the disease. Unlike traditional diagnostic methods that often rely on a combination of clinical evaluations and MRI findings, this approach aims to provide a more precise, singular marker by identifying central veins in brain lesions via MRI scans. This could potentially lead to quicker, more accurate diagnoses, reducing the uncertainty and delay often experienced with current diagnostic practices. If successful, this method could significantly enhance the ability of clinicians to diagnose MS earlier and more reliably.

What evidence suggests that the Central Vein Sign is effective for improving MS diagnosis?

Research shows that the Central Vein Sign (CVS) could be a valuable tool for diagnosing Multiple Sclerosis (MS). Studies have found that about 49% of MS-related brain spots display the CVS, compared to only 24% in non-MS cases. This suggests that the CVS might help doctors distinguish MS from other conditions more accurately. The trial will evaluate the use of CVS in patients with both typical and atypical symptom onset. Using CVS could make diagnosing MS faster and more precise, which is crucial for starting treatment early. Early results indicate that using CVS as a biological marker might reduce misdiagnoses and unnecessary treatments. ^{1 2 6 7 8}

Who Is on the Research Team?

Daniel Ontaneda, MD, PhD

Principal Investigator

The Cleveland Clinic

Nancy Sicotte, MD

Principal Investigator

Cedars-Sinai Medical Center

Pascal Sati, PhD

Principal Investigator

Cedars-Sinai Medical Center

Are You a Good Fit for This Trial?

Inclusion Criteria

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.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Initial assessments including MRI and lab tests to establish baseline data

1 visit

1 visit (in-person)

Follow-up

Participants are monitored for disease progression and diagnostic accuracy using CVS criteria

24 months

5 visits (in-person) at baseline, month 6, month 12, month 18, and month 24

What Are the Treatments Tested in This Trial?

Interventions

• Central Vein Sign

How Is the Trial Designed?

Group I: Typical Experimental Treatment 1 Intervention

Patients 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 (central nervous system) pattern, Lhermitte's symptom, asymmetric limb weakness, urge incontinence or erectile dysfunction, or other neurological presentation considered to be typical by the site investigator.

Group II: Atypical Experimental Treatment 1 Intervention

Patients 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.

Who Is Running the Clinical Trial?

The Cleveland Clinic

Lead Sponsor

Trials

1,072

Recruited

1,377,000+

Cedars-Sinai Medical Center

Collaborator

Trials

523

Recruited

165,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

University of Pennsylvania

Collaborator

Trials

2,118

Recruited

45,270,000+

National Institute of Neurological Disorders and Stroke (NINDS)

Collaborator

Trials

1,403

Recruited

655,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8482479/

Central vein sign: biomarker in multiple sclerosis study protocol CAVS-MS is a prospective multicenter study to validate the central vein. CAVS-MS will useT2*-weighted, high-isotropic-resolution, segmented echo-planar MRI.

2. neurology.org neurology.org/doi/10.1212/WN9.0000000000000031

Prevalence of Central Vein Sign in Pediatric MS | Neurology By contrast, another report on 19 adult patients with MS showed CVS only in a relatively low proportion of MS lesions (40.9%) at 1.5T SWI MRI, ...

3. nature.com nature.com/articles/nrneurol.2016.166

Central Vein Sign in Multiple Sclerosis Diagnosis The central vein sign (CVS) has recently been proposed as a novel MRI biomarker to improve the accuracy and speed of MS diagnosis.

4. sciencedirect.com sciencedirect.com/science/article/pii/S0378603X1730222X

Value of Central Vein Sign in MS Plaques vs. Lesions Out of 572 MS lesions, 281 lesions (49.13%) were positive for the central vein sign, while 66 out of 279 non-MS lesions (23.6%) were positive for the central ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04495556

NCT04495556 | Central Vein Sign: a Diagnostic Biomarker ... The CVS is proposed as a diagnostic biomarker with improved sensitivity for a diagnosis of MS, while retaining diagnostic specificity - all in an-easy-to use ...

6. practicalneurology.com practicalneurology.com/diseases-diagnoses/imaging-testing/the-central-vein-sign/31627/

Central Vein Sign in MS Diagnosis - - Practical Neurology Analysis of 4,447 lesions in 487 people with MS who had 3T MRI at 1 of multiple sites showed sensitivity of 68.1% and specificity of 82.9% for ...

7. nature.com nature.com/articles/s41598-019-54583-3

The “Central Vein Sign” on T2*-weighted Images as a ... The current evidence supports the use of the central vein sign on T2*-weighted images to differentiate MS from other white matter lesions.

8. jamanetwork.com jamanetwork.com/journals/jamaneurology/fullarticle/2812783

Diagnostic Performance of Cortical Lesions and the ... This cross-sectional study evaluates the use of cortical lesions and central vein sign in distinguishing multiple sclerosis from other ...