Efficacy of COVID-19 Vaccination in Patients With Multiple Sclerosis Treated With Immune Modulating Medication

Efficacy of COVID 19 SARS-CoV-2 mRNA Vaccination in Patients With Multiple Sclerosis Treated With Immune Modulating Medication (SARSmRNA_MS)

The primary objective is to determine whether the use of immunomodulating medications have an impact on the ability to mount and sustain an immune response to SARS-CoV-2 spike protein following mRNA vaccination in patients with MS when compared to healthy controls not receiving immunomodulating medications.

We hypothesize that the use of immunomodulators in MS patients may eliminate or reduce the level of protective immune response, and/or shorten the duration of the protective response.

Study Overview

• Status: Terminated
• Conditions: Multiple Sclerosis
• Intervention / Treatment: Other: Analysis of cell-mediated and antibody-mediated immunity to SARS-CoV-2 virus

Detailed Description

Analysis of cell-mediated and antibody-mediated immunity to the COVID-19, SARS-CoV-2 virus following treatment with mRNA vaccine, in patients with multiple sclerosis (MS) who are treated with immune modulating medication. Each consenting subject will provide approximately 30 mL of whole blood via venipuncture before their first vaccine injection (those who meet inclusion 3a only), 45 (those who meet inclusion 3a or 3b), 90 and 180 days after the first vaccine injection (those who meet inclusion 3a, 3b, or 3c). If they receive a booster vaccine injection, they will also be asked to provide 30 mL of whole blood 28-42 days after the booster injection date. These samples, obtained at Providence St. Vincent Medical Center, will be transferred to the Laboratory of Molecular and Tumor Immunology at the Earle A. Chiles Cancer Research Institute, where the blood will be processed and cryopreserved. Serum samples will be analyzed for the presence and titer of neutralizing antibodies to the SARS-CoV-2 virus. Isolated peripheral blood lymphocytes will be used for analyses of T cell responses to SARS-CoV-2 spike peptides. Responses will be compared to the immune responses of 10 subjects who have been enrolled in the CORVax spike plasmid DNA vaccine study and are subsequently referred to in this protocol as "healthy controls." The unused portion of the samples will be stored for future deep cytokine and genomic analyses if funding becomes available to perform these latter studies.

This study will include 4 cohorts, each will enroll 10 subjects who are being treated with an immunomodulating therapy for MS. The 4 immunomodulating medications selected, because each differs in their mechanisms of action, include ocrelizumab (B-cell lytic), fingolimod (prevents mobilization of B and T cells from peripheral lymphoid organs), natalizumab (blocks transmigration of monocytes, and lymphocytes into the central nervous system), and dimethyl fumarate/diroximel fumarate (reduces inflammation-induce oxidative stress).

• Study Type: Observational
• Enrollment (Actual): 20

Contacts and Locations

Study Locations

• United States
  • Oregon
    • Portland, Oregon, United States, 97225
      • Providence Neurological Specialties West

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

There is no available information on whether patients being treated with immunomodulating agents will mount a response to SARS-CoV-2 vaccination comparable to that observed in the general population. Volunteers will be recruited from the MS patient population cared for at the Providence MS Center. Patients will be identified by review of electronic medical records. Patients who appear to meet the eligibility criteria will be contacted by an investigator and/or a delegated research staff member.

Description

Inclusion Criteria:

1. Able to understand the purpose, benefits, and risks of the study; willing and able to adhere to the study requirements; able to provide informed consent in English
2. Male or female, between the ages of 18 and 65 years inclusive at time of consent

3. Meet one of the following:

   1. Plan to receive one of the FDA approved mRNA-based COVID SARS-CoV-2 vaccinations within 30 days of the screening visit
   2. Have received one of the FDA approved mRNA-based COVID SARS-CoV-2 vaccinations, their first vaccine injection having occurred 45±7 days prior to the screening visit
   3. Have received one of the FDA approved mRNA-based COVID SARS-CoV-2 vaccinations, their first vaccine injection having occurred 90±7 days prior to the screening visit
4. Meet the criteria of one of the four groups at the time of consent:

Group 1: Diagnosed with multiple sclerosis and currently being treated with a stable dose of ocrelizumab, for 6 months or longer Group 2: Diagnosed with multiple sclerosis and currently being treated with a stable dose of fingolimod, for 6 months or longer Group 3: Diagnosed with multiple sclerosis and currently being treated with a stable dose of natalizumab, for 6 months or longer Group 4: Diagnosed with multiple sclerosis and currently being treated with a stable dose of dimethyl fumarate or diroximel fumarate, for 6 months or longer

Exclusion Criteria:

1. Subjects who have a BMI of >35.0 will be excluded

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
MS subjects who are being treated with ocrelizumab; Ocrelizumab's immunomodulating mechanisms of action is B-cell lytic. Each consenting subject will provide approximately 30 mL of whole blood via venipuncture before and 45, 90 and 180 days after the first vaccine injection and 28-42 days after the booster vaccination (if applicable).	Other: Analysis of cell-mediated and antibody-mediated immunity to SARS-CoV-2 virus; mRNA vaccination for SARS-CoV-2 is not provided by the study
MS subjects who are being treated with fingolimod; Fingolimod's immunomodulating mechanisms of action is to prevent mobilization of B and T cells from peripheral lymphoid organs. Each consenting subject will provide approximately 30 mL of whole blood via venipuncture before and 45, 90 and 180 days after the first vaccine injection and 28-42 days after the booster vaccination (if applicable).	Other: Analysis of cell-mediated and antibody-mediated immunity to SARS-CoV-2 virus; mRNA vaccination for SARS-CoV-2 is not provided by the study
MS subjects who are being treated with natalizumab; Natalizumab's immunomodulating mechanisms of action is to block transmigration of monocytes, and lymphocytes into the central nervous system. Each consenting subject will provide approximately 30 mL of whole blood via venipuncture before and 45, 90 and 180 days after the first vaccine injection and 28-42 days after the booster vaccination (if applicable).	Other: Analysis of cell-mediated and antibody-mediated immunity to SARS-CoV-2 virus; mRNA vaccination for SARS-CoV-2 is not provided by the study
MS subjects who are being treated with dimethyl fumarate/diroximel fumarate; Dimethyl Fumarate's immunomodulating mechanisms of action is to reduce inflammation-induced oxidative stress. Each consenting subject will provide approximately 30 mL of whole blood via venipuncture before and 45, 90 and 180 days after the first vaccine injection and 28-42 days after the booster vaccination (if applicable).	Other: Analysis of cell-mediated and antibody-mediated immunity to SARS-CoV-2 virus; mRNA vaccination for SARS-CoV-2 is not provided by the study

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Titer of antibody against SARS-CoV-2 spike protein	Serum Sample	Day 45 following initial vaccination
Quantity of IFN-g secreted in response to stimulation with SARS-CoV-2 spike protein	Serum Sample	Day 45 following initial vaccination
Quantity of TNF-a secreted in response to stimulation with SARS-CoV-2 spike protein	Serum Sample	Day 45 following initial vaccination

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Titer of antibody against SARS-CoV-2 spike protein	Serum Sample	Day 90 following initial vaccination
Quantity of IFN-g secreted in response to stimulation with SARS-CoV-2 spike protein	Serum Sample	Day 90 following initial vaccination
Quantity of TNF-a secreted in response to stimulation with SARS-CoV-2 spike protein	Serum Sample	Day 90 following initial vaccination
Titer of antibody against SARS-CoV-2 spike protein	Serum Sample	Day 180 following initial vaccination
Quantity of IFN-g secreted in response to stimulation with SARS-CoV-2 spike protein	Serum Sample	Day 180 following initial vaccination
Titer of antibody against SARS-CoV-2 spike protein	Serum Sample	28-42 days following booster vaccination
Quantity of TNF-a secreted in response to stimulation with SARS-CoV-2 spike protein	Serum Sample	28-42 days following booster vaccination
Quantity of IFN-g secreted in response to stimulation with SARS-CoV-2 spike protein	Serum Sample	28-42 days following booster vaccination

Collaborators and Investigators

• Sponsor: Providence Health & Services
• Investigators: Principal Investigator: Stanley Cohan, MD PhD, Providence Health & Services

Publications and helpful links

General Publications

• Mohn N, Konen FF, Pul R, Kleinschnitz C, Pruss H, Witte T, Stangel M, Skripuletz T. Experience in Multiple Sclerosis Patients with COVID-19 and Disease-Modifying Therapies: A Review of 873 Published Cases. J Clin Med. 2020 Dec 16;9(12):4067. doi: 10.3390/jcm9124067.
• Kataria S, Tandon M, Melnic V, Sriwastava S. A case series and literature review of multiple sclerosis and COVID-19: Clinical characteristics, outcomes and a brief review of immunotherapies. eNeurologicalSci. 2020 Dec;21:100287. doi: 10.1016/j.ensci.2020.100287. Epub 2020 Nov 2.
• Sormani MP; Italian Study Group on COVID-19 infection in multiple sclerosis. An Italian programme for COVID-19 infection in multiple sclerosis. Lancet Neurol. 2020 Jun;19(6):481-482. doi: 10.1016/S1474-4422(20)30147-2. Epub 2020 Apr 30. No abstract available. Erratum In: Lancet Neurol. 2020 May 28;:
• Louapre C, Collongues N, Stankoff B, Giannesini C, Papeix C, Bensa C, Deschamps R, Creange A, Wahab A, Pelletier J, Heinzlef O, Labauge P, Guilloton L, Ahle G, Goudot M, Bigaut K, Laplaud DA, Vukusic S, Lubetzki C, De Seze J; Covisep investigators; Derouiche F, Tourbah A, Mathey G, Theaudin M, Sellal F, Dugay MH, Zephir H, Vermersch P, Durand-Dubief F, Francoise R, Androdias-Condemine G, Pique J, Codjia P, Tilikete C, Marcaud V, Lebrun-Frenay C, Cohen M, Ungureanu A, Maillart E, Beigneux Y, Roux T, Corvol JC, Bordet A, Mathieu Y, Le Breton F, Boulos DD, Gout O, Gueguen A, Moulignier A, Boudot M, Chardain A, Coulette S, Manchon E, Ayache SS, Moreau T, Garcia PY, Kumaran D, Castelnovo G, Thouvenot E, Taithe F, Poupart J, Kwiatkowski A, Defer G, Derache N, Branger P, Biotti D, Ciron J, Clerc C, Vaillant M, Magy L, Montcuquet A, Kerschen P, Coustans M, Guennoc AM, Brochet B, Ouallet JC, Ruet A, Dulau C, Wiertlewski S, Berger E, Buch D, Bourre B, Pallix-Guiot M, Maurousset A, Audoin B, Rico A, Maarouf A, Edan G, Papassin J, Videt D. Clinical Characteristics and Outcomes in Patients With Coronavirus Disease 2019 and Multiple Sclerosis. JAMA Neurol. 2020 Sep 1;77(9):1079-1088. doi: 10.1001/jamaneurol.2020.2581.

Study record dates

Study Major Dates

• Study Start (Actual): July 11, 2022
• Primary Completion (Actual): October 4, 2022
• Study Completion (Actual): October 25, 2022

Study Registration Dates

• First Submitted: March 11, 2021
• First Submitted That Met QC Criteria: March 11, 2021
• First Posted (Actual): March 15, 2021

Study Record Updates

• Last Update Posted (Actual): April 3, 2023
• Last Update Submitted That Met QC Criteria: March 30, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: mRNA-based SARS-CoV-2 vaccination
• 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; Physiological Effects of Drugs; Immunologic Factors; Antibodies
• Other Study ID Numbers: SARSmRNA_MS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Study data will be kept in secure computer files, in locked research offices that are both only accessible to research personnel, and in a secure password protected Clinical Trial Management System (CTMS). Publications or presentations will report aggregate data and will not contain any subject identification.

Drug and device information, study documents

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