Sema4A MS: Sema 4A as a Marker for Inflammatory Disease in Multiple Sclerosis

Sponsor

Providence Health & Services (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT05077956

Collaborator

Milton S. Hershey Medical Center (Other), Bristol-Myers Squibb (Industry)

Enrollment

Location

24.2

Anticipated Duration (Months)

1.7

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Relapsing Multiple Sclerosis Multiple Sclerosis	Diagnostic Test: Cerebrospinal and Blood Serum Semaphorin 4A Levels

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.

Study Design

Study Type:

Observational

Anticipated Enrollment :

40 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Sema 4A as a Marker for Inflammatory Disease in Multiple Sclerosis

Actual Study Start Date :

Oct 19, 2021

Anticipated Primary Completion Date :

Oct 25, 2023

Anticipated Study Completion Date :

Oct 25, 2023

Arms and Interventions

Arm	Intervention/Treatment
Recently Diagnosed Multiple Sclerosis Recently diagnosed MS, who 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 (DMT).	Diagnostic Test: Cerebrospinal and Blood Serum Semaphorin 4A Levels Cerebrospinal fluid and serum will be collected at baseline to measure the level of semaphorin 4A.
Clinically Stable Relapsing Multiple Sclerosis Clinically stable relapsing MS, who are receiving a FDA-approved MS DMT and have had no evidence of a clinical relapse for at least the past 12 weeks or gadolinium enhancing lesions on MRI in the prior 4 weeks.	Diagnostic Test: Cerebrospinal and Blood Serum Semaphorin 4A Levels Cerebrospinal fluid and serum will be collected at baseline to measure the level of semaphorin 4A.
Relapsing Multiple Sclerosis on Disease Modifying Therapy Relapsing MS on a FDA-approved DMT with evidence of recent breakthrough disease, with a documented clinical relapse and/or gadolinium-enhancing lesion(s) on brain or spinal cord MRI taken within the 4 weeks.	Diagnostic Test: Cerebrospinal and Blood Serum Semaphorin 4A Levels Cerebrospinal fluid and serum will be collected at baseline to measure the level of semaphorin 4A.
Healthy Volunteers Patients 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.	Diagnostic Test: Cerebrospinal and Blood Serum Semaphorin 4A Levels Cerebrospinal fluid and serum will be collected at baseline to measure the level of semaphorin 4A.

Outcome Measures

Primary Outcome Measures

Blood Serum Semaphorin 4A Levels [Baseline]
Measure blood serum semaphorin 4A levels at baseline
Cerebrospinal Fluid Semaphorin 4A Levels [Baseline]
Measure cerebrospinal fluid semaphorin 4A levels at baseline

Secondary Outcome Measures

Correlation between Semaphorin 4A levels and Demyelination and Axonal Degeneration [12 Months]
MRI will be performed at 6 months and 12 months to evaluate if there is a correlation between baseline semaphorin 4 A levels and demyelination and axonal degeneration.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 55 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Yes

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