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

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).

Study Overview

• Status: Withdrawn
• Conditions: Multiple Sclerosis; Relapsing Multiple Sclerosis
• Intervention / Treatment: 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 Type: Observational

Contacts and Locations

Study Locations

• United States
  • Oregon
    • Portland, Oregon, United States, 97225
      • Providence St. Vincent Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Probability Sample

Study Population

Multiple sclerosis and non-MS controls

Description

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.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood Serum Semaphorin 4A Levels	Measure blood serum semaphorin 4A levels at baseline	Baseline
Cerebrospinal Fluid Semaphorin 4A Levels	Measure cerebrospinal fluid semaphorin 4A levels at baseline	Baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation between Semaphorin 4A levels and Demyelination and Axonal Degeneration	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.	12 Months

Collaborators and Investigators

• Sponsor: Providence Health & Services
• Collaborators: Bristol-Myers Squibb; Milton S. Hershey Medical Center
• Investigators: Principal Investigator: Stanley Cohan, MD, PhD, Providence Health and Services

Study record dates

Study Major Dates

• Study Start (Actual): October 19, 2021
• Primary Completion (Estimated): October 25, 2023
• Study Completion (Estimated): October 25, 2023

Study Registration Dates

• First Submitted: October 1, 2021
• First Submitted That Met QC Criteria: October 1, 2021
• First Posted (Actual): October 14, 2021

Study Record Updates

• Last Update Posted (Actual): August 7, 2023
• Last Update Submitted That Met QC Criteria: August 2, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: biomarker; multiple sclerosis; relapsing multiple sclerosis; semaphorin 4A; sema4a; disease modifying therapy
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis
• Other Study ID Numbers: 2021000250

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No