Clinical trial NCT05077956: Sema 4A as a Marker for Inflammatory Disease in Multiple Sclerosis
Official title: Sema 4A as a Marker for Inflammatory Disease in Multiple Sclerosis
Study type: OBSERVATIONAL
Overall status: WITHDRAWN
Conditions: Relapsing Multiple Sclerosis
Multiple Sclerosis
Keywords: multiple sclerosis
relapsing multiple sclerosis
semaphorin 4A
sema4a
disease modifying therapy
biomarker
Lead sponsor: Providence Health & Services
Sponsor class: OTHER
Collaborators: name: Milton S. Hershey Medical Center
name: Bristol-Myers Squibb
First posted: 2021-10-14
Enrollment: 0
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Multiple sclerosis and non-MS controls

Brief summary: Measure serum and cerebrospinal fluid Sema4A levels in female subjects with newly diagnosed and untreated relapsing multiple sclerosis, clinically stable relapsing multiple sclerosis receiving disease modifying therapy, relapsing multiple sclerosis receiving disease modifying therapy with breakthrough disease, or non-multiple sclerosis controls (patients without inflammatory central nervous system disease).

Detailed description: This pilot study proposal will further investigate whether Semaphorin 4A (Sema4A) elevation in cerebrospinal fluid (CSF) and serum is a potential disease activity biomarker in patients with multiple sclerosis (MS).

A total of 40 female subjects between the ages of 18-55 who meet the criteria of one of the following four groups will be enrolled to measure serum and CSF Sema4A levels:

* Group 1: Newly diagnosed/untreated Relapsing MS patients (RMS)
* Group 2: Clinically stable RMS patients receiving disease modifying therapy (DMT)
* Group 3: RMS patients receiving DMT with breakthrough disease
* Group 4: Non-MS controls (patients without inflammatory CNS disease)

Participants will provide blood and CSF samples at baseline for Sema4A analysis. Follow up blood samples will be collected at 6 months and 12 months as part of lymphocyte subset analysis. Participation will end after 12 months of follow up.

The expected risks are related to blood draws and lumbar puncture. Lumbar puncture will be performed under fluoroscopy to decrease risks of pain from repeated needle punctures, injury from incorrect placement of the needle, and post puncture CSF leakage.

Eligibility criteria: Inclusion Criteria:

* Female aged 18-55, inclusive at the time of consent
* Not pregnant at the time of the screening/baseline visit
* Able to understand the purpose, benefits, and risks of the study; willing and able to adhere to the study requirements; able and provide informed consent in English
* Meet the criteria of one of the four groups at the time of consent:

  * Group 1: subjects who have recently been diagnosed with MS, have had a clinical attack within the last 6 months, have not received steroids in the last 30 days, and have not started on a disease modifying therapy
  * Group 2: subjects with clinically stable relapsing MS, with no evidence of clinical relapse for at least the past 12 weeks, and have no gadolinium enhancing lesions on MRI in the prior 4 weeks, who are receiving a FDA-approved MS DMT
  * Group 3: subjects with relapsing MS on a FDA-approved DMT but with evidence of breakthrough disease, with a documented clinical relapse and/or gadolinium-enhancing lesion(s) on brain or spinal cord MRI taken within the 4 weeks
  * Group 4: subjects without evidence of inflammatory systemic or CNS disease, who require CSF removal for some other cause, such as for idiopathic intracranial hypertension or communicating hydrocephalus

Exclusion Criteria:

* There are no exclusion criteria for this study.

Primary outcomes:
measure: Blood Serum Semaphorin 4A Levels
timeFrame: Baseline
measure: Cerebrospinal Fluid Semaphorin 4A Levels
timeFrame: Baseline
Secondary outcomes:
measure: Correlation between Semaphorin 4A levels and Demyelination and Axonal Degeneration
timeFrame: 12 Months
Other outcomes:
Locations:
city: Portland
country: United States
facility: Providence St. Vincent Medical Center
state: Oregon
Study officials:
affiliation: Providence Health and Services
name: Stanley Cohan, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: