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

NCT04796584 | Terminated

• 1 other identifier: SARSmRNA_MS
• Study Type: observational
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Multiple Sclerosis

Keywords

mRNA-based SARS-CoV-2 vaccination

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (8)

• Titer of antibody against SARS-CoV-2 spike protein

  Day 90 following initial vaccination

• Quantity of IFN-g secreted in response to stimulation with SARS-CoV-2 spike protein

  Day 90 following initial vaccination

• Quantity of TNF-a secreted in response to stimulation with SARS-CoV-2 spike protein

  Day 90 following initial vaccination

• Titer of antibody against SARS-CoV-2 spike protein

  Day 180 following initial vaccination

• Quantity of IFN-g secreted in response to stimulation with SARS-CoV-2 spike protein

  Day 180 following initial vaccination

Study Arms (4)

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

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

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

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

Interventions

Analysis of cell-mediated and antibody-mediated immunity to SARS-CoV-2 virus OTHER

mRNA vaccination for SARS-CoV-2 is not provided by the study

MS subjects who are being treated with dimethyl fumarate/diroximel fumarate; MS subjects who are being treated with fingolimod; MS subjects who are being treated with natalizumab; MS subjects who are being treated with ocrelizumab

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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
• Male or female, between the ages of 18 and 65 years inclusive at time of consent
• Meet one of the following:
• Plan to receive one of the FDA approved mRNA-based COVID SARS-CoV-2 vaccinations within 30 days of the screening visit
• 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
• 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
• 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

You may not qualify if:

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

Sponsors & Collaborators

• Providence Health & Services: lead

Study Sites (1)

Providence Neurological Specialties West

Portland, Oregon, 97225, United States

Location

Related Publications (4)

• 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.

  PMID: 33163634 BACKGROUND

• 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.

  PMID: 33339436 BACKGROUND

• 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.

  PMID: 32359409 BACKGROUND

• 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.

  PMID: 32589189 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Serum samples will be analyzed for the presence and titer of neutralizing antibodies to the SARSCoV-2 virus. Isolated peripheral blood lymphocytes will be used for analyses of T cell responses to SARS-CoV-2 spike peptides. 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. Data and samples will be stored indefinitely. It is possible that disease specific genetic testing, as it relates to the Donor's diagnosis of autoimmunity and their immune response to the vaccine and/or their autologous tissue, may be done on samples. Other testing may be done as technology and scientific knowledge about the immune response to vaccines and autoimmunity advances

MeSH Terms

Conditions

Multiple Sclerosis

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Stanley Cohan, MD PhD

  Providence Health & Services

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 11, 2021
• First Posted: March 15, 2021
• Study Start: July 11, 2022
• Primary Completion: October 4, 2022
• Study Completion: October 25, 2022
• Last Updated: April 3, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)