NCT04300868

Brief Summary

Multiple sclerosis (MS) patients are more susceptible to infections than the general population in relation to some specific therapies or increasing disability. Clearly, the use of immuno-suppressant/modulatory drugs requires particular attention to the occurrence of infectious events. In this perspective, among still unmet clinical needs in MS patients is a comprehensive picture on the immunisation status against infectious diseases, especially those preventable with vaccines. Despite of the relevance of vaccinations, there are still some concerns about their utilization in MS patients. In literature, results about their safety are conflicting or incomplete and it is yet unclear if some vaccines may trigger MS relapses. GOALS: 1) to assess immunisation status, due to past exposure to natural infectious diseases or vaccines, against major infectious agents preventable by available vaccines; 2) to assess the safety of most utilized vaccines in the clinical practice by recording relapses as adverse event in the considered risk period after vaccination. The 3-year project is conceived as a multicenter, observational, both retro- and prospective study. A cohort of about 3,000 MS subjects will be enrolled among databases of 25 clinical Centers in Italy. All patients diagnosed with relapsing remitting (RR) MS according to the 2010 Polman's criteria from 01/2011 to 12/2020 will be enrolled. Available data on natural immunisation will be collected from the historical clinical records of Centers, taking into account the presence of specific serum antibodies, whereas available data on vaccinations will be collected from vaccination records. To study the impact of vaccines on the risk of relapse, data about patients receiving a vaccination during the disease will be analysed. The study follow-up period will be between 2 and up to 6 months following vaccination: the 2-month period is considered as the maximum clinical risk, whereas 6 months as the maximal extension of risk in time. In addition, in the case of a clinical relapse, the variation of disability will be evaluated with EDSS scale confirmed at 6 months. These data might shed light on the relationship between vaccination and MS, adding new insights on their safety. The knowledge of the immunisation status is crucial for the clinical practice in the management of the new disease modifying drugs (DMDs), and for the public health to establish the possible need of a vaccine campaign targeted to MS patients.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
3,000

participants targeted

Target at P75+ for all trials

Timeline
Completed

Started Mar 2019

Longer than P75 for all trials

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

March 20, 2019

Completed
12 months until next milestone

First Submitted

Initial submission to the registry

March 5, 2020

Completed
4 days until next milestone

First Posted

Study publicly available on registry

March 9, 2020

Completed
2.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 31, 2023

Completed
2 months until next milestone

Study Completion

Last participant's last visit for all outcomes

March 31, 2023

Completed
Last Updated

November 16, 2022

Status Verified

November 1, 2022

Enrollment Period

3.9 years

First QC Date

March 5, 2020

Last Update Submit

November 15, 2022

Conditions

Multiple Sclerosis

Keywords

immunisation statusvaccine safetyvaccination

Outcome Measures

Primary Outcomes (1)

  • prevalence of MS patients susceptible to infections

    prevalence of patients unvaccinated or never exposed to natural infections, which can represent a problem in case of administration of immunosuppresive drugs.

    december 2021

Secondary Outcomes (1)

  • safety of vaccination in MS patients

    december 2021

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)
Sampling MethodNon-Probability Sample
Study Population

Relapsing remitting (RR)-MS patients consecutively diagnosed from January 2011 to December 2020 will be enrolled in the study upon informed written consent. The choice of January 2011 is suggested by the need to apply the 2010 Polman's diagnostic criteria for MS \[Polman 2011\] in order to ensure most homogeneous diagnoses across patients. Both for retrospective and prospective phase, each Center will identify, through clinical records, newly diagnosed MS patients in the considered period and consistently followed in the Center, and the enrolment will be made during routine ambulatory visits.

You may qualify if:

  • diagnosis of RR-MS according to the 2010 Polman's diagnostic criteria \[Polman 2011\] or the 2017 revision of the McDonald criteria for the prospective cohort \[Thompson 2018\]
  • written informed consent must be obtained before the enrolment

You may not qualify if:

  • clinically isolated syndrome (CIS) and progressive MS forms
  • unavailability or unreliability of medical records

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

university of Siena

Siena, SI, 53100, Italy

RECRUITING

Related Publications (27)

  • Cahill JFX, Izzo A, Garg N (2010) Immunisation in patients with Multiple Sclerosis. Neurol. Bull, 2:17-21. 10.7191/neurol_bull.2010.1020

    BACKGROUND

  • Farez MF, Correale J. Yellow fever vaccination and increased relapse rate in travelers with multiple sclerosis. Arch Neurol. 2011 Oct;68(10):1267-71. doi: 10.1001/archneurol.2011.131. Epub 2011 Jun 13.

    PMID: 21670384BACKGROUND

  • Galeotti F, Massari M, D'Alessandro R, Beghi E, Chio A, Logroscino G, Filippini G, Benedetti MD, Pugliatti M, Santuccio C, Raschetti R; ITANG study group. Risk of Guillain-Barre syndrome after 2010-2011 influenza vaccination. Eur J Epidemiol. 2013 May;28(5):433-44. doi: 10.1007/s10654-013-9797-8. Epub 2013 Mar 31.

    PMID: 23543123BACKGROUND

  • Kohlmann R, Salmen A, Chan A, Knabbe C, Diekmann J, Brockmeyer N, Skaletz-Rorowski A, Michalik C, Gold R, Uberla K. Serological evidence of increased susceptibility to varicella-zoster virus reactivation or reinfection in natalizumab-treated patients with multiple sclerosis. Mult Scler. 2015 Dec;21(14):1823-32. doi: 10.1177/1352458515576984. Epub 2015 Mar 31.

    PMID: 25828755BACKGROUND

  • Lobermann M, Borso D, Hilgendorf I, Fritzsche C, Zettl UK, Reisinger EC. Immunization in the adult immunocompromised host. Autoimmun Rev. 2012 Jan;11(3):212-8. doi: 10.1016/j.autrev.2011.05.015. Epub 2011 May 18.

    PMID: 21621004BACKGROUND

  • Loebermann M, Winkelmann A, Hartung HP, Hengel H, Reisinger EC, Zettl UK. Vaccination against infection in patients with multiple sclerosis. Nat Rev Neurol. 2012 Jan 24;8(3):143-51. doi: 10.1038/nrneurol.2012.8.

    PMID: 22270022BACKGROUND

  • Mailand MT, Frederiksen JL. Vaccines and multiple sclerosis: a systematic review. J Neurol. 2017 Jun;264(6):1035-1050. doi: 10.1007/s00415-016-8263-4. Epub 2016 Sep 7.

    PMID: 27604618BACKGROUND

  • Montgomery S, Hillert J, Bahmanyar S. Hospital admission due to infections in multiple sclerosis patients. Eur J Neurol. 2013 Aug;20(8):1153-60. doi: 10.1111/ene.12130. Epub 2013 Mar 16.

    PMID: 23496086BACKGROUND

  • MS council for clinical practice guideline. Immunisation and multiple sclerosis. Evidence-Based Management Strategies for Immunisations in Multiple Sclerosis. Nov 2001

    BACKGROUND

  • National MS society Vaccinations https://www.nationalmssociety.org/Living-Well-With-MS/Diet-Exercise-Healthy-Behaviors/Vaccinations

    BACKGROUND

  • Nelson RE, Xie Y, DuVall SL, Butler J, Kamauu AW, Knippenberg K, Schuerch M, Foskett N, LaFleur J. Multiple Sclerosis and Risk of Infection-Related Hospitalization and Death in US Veterans. Int J MS Care. 2015 Sep-Oct;17(5):221-30. doi: 10.7224/1537-2073.2014-035.

    PMID: 26472943BACKGROUND

  • Nix EB, Hawdon N, Gravelle S, Biman B, Brigden M, Malik S, McCready W, Ferroni G, Ulanova M. Risk of invasive Haemophilus influenzae type b (Hib) disease in adults with secondary immunodeficiency in the post-Hib vaccine era. Clin Vaccine Immunol. 2012 May;19(5):766-71. doi: 10.1128/CVI.05675-11. Epub 2012 Mar 7.

    PMID: 22398246BACKGROUND

  • Olsson T. The new era of multiple sclerosis therapy. J Intern Med. 2014 Apr;275(4):382-6. doi: 10.1111/joim.12196. Epub 2014 Mar 15. No abstract available.

    PMID: 24433367BACKGROUND

  • Oreja-Guevara C, Wiendl H, Kieseier BC, Airas L; NeuroNet Study Group. Specific aspects of modern life for people with multiple sclerosis: considerations for the practitioner. Ther Adv Neurol Disord. 2014 Mar;7(2):137-49. doi: 10.1177/1756285613501575.

    PMID: 24587828BACKGROUND

  • Orlicka K, Barnes E, Culver EL. Prevention of infection caused by immunosuppressive drugs in gastroenterology. Ther Adv Chronic Dis. 2013 Jul;4(4):167-85. doi: 10.1177/2040622313485275.

    PMID: 23819020BACKGROUND

  • Panitch HS. Influence of infection on exacerbations of multiple sclerosis. Ann Neurol. 1994;36 Suppl(Suppl ):S25-8. doi: 10.1002/ana.410360709.

    PMID: 8017885BACKGROUND

  • Polman CH, Reingold SC, Banwell B, Clanet M, Cohen JA, Filippi M, Fujihara K, Havrdova E, Hutchinson M, Kappos L, Lublin FD, Montalban X, O'Connor P, Sandberg-Wollheim M, Thompson AJ, Waubant E, Weinshenker B, Wolinsky JS. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol. 2011 Feb;69(2):292-302. doi: 10.1002/ana.22366.

    PMID: 21387374BACKGROUND

  • Rutschmann OT, McCrory DC, Matchar DB; Immunization Panel of the Multiple Sclerosis Council for Clinical Practice Guidelines. Immunization and MS [RETIRED]: a summary of published evidence and recommendations. Neurology. 2002 Dec 24;59(12):1837-43. doi: 10.1212/wnl.59.12.1837.

    PMID: 12499473BACKGROUND

  • Steelman AJ. Infection as an Environmental Trigger of Multiple Sclerosis Disease Exacerbation. Front Immunol. 2015 Oct 19;6:520. doi: 10.3389/fimmu.2015.00520. eCollection 2015.

    PMID: 26539193BACKGROUND

  • Vaccines.gov https://www.vaccines.gov/basics/types/index.html

    BACKGROUND

  • Williamson EM, Berger JR. Infection risk in patients on multiple sclerosis therapeutics. CNS Drugs. 2015 Mar;29(3):229-44. doi: 10.1007/s40263-015-0226-2.

    PMID: 25761739BACKGROUND

  • Williamson EM, Chahin S, Berger JR. Vaccines in Multiple Sclerosis. Curr Neurol Neurosci Rep. 2016 Apr;16(4):36. doi: 10.1007/s11910-016-0637-6.

    PMID: 26922172BACKGROUND

  • Winkelmann A, Loebermann M, Reisinger EC, Hartung HP, Zettl UK. Disease-modifying therapies and infectious risks in multiple sclerosis. Nat Rev Neurol. 2016 Apr;12(4):217-33. doi: 10.1038/nrneurol.2016.21. Epub 2016 Mar 4.

    PMID: 26943779BACKGROUND

  • www.cdc.gov Adults with chronic conditions: get vaccinated. Available from https://www.cdc.gov/features/vaccineschronicconditions/index.html. Accessed May 13, 2018.

    BACKGROUND

  • www.ecdc.europa.eu Seasonal influenza vaccines. Influenza vaccination. Available from: http://ecdc.europa.eu/en/healthtopics/seasonal_influenza/vaccines/Pages/ influenza_vaccination.aspx#vaccinationstrategies. Accessed May 13, 2018

    BACKGROUND

  • www.salute.gov Ministero della salute. Vaccinazioni http://www.salute.gov.it/portale/vaccinazioni/homeVaccinazioni.jsp

    BACKGROUND

  • • Yang SH, Hsu C, Cheng AL, Kuo SH (2014) Anti-CD20 monoclonal antibodies and associated viral hepatitis in hematological diseases. World J Hematol, 3(2):29-43

    BACKGROUND

MeSH Terms

Conditions

Multiple Sclerosis

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNSAutoimmune Diseases of the Nervous SystemNervous System DiseasesDemyelinating DiseasesAutoimmune DiseasesImmune System Diseases

Study Officials

  • Monica Ulivelli, researcher

    University of Siena

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Monica Ulivelli, researcher

CONTACT

0577585401ulivelli@unisi.it

Daiana Bezzini, PhD

CONTACT

0577234517daiana.bezzini@unisi.it

Study Design

Study Type
observational
Observational Model
OTHER
Time Perspective
OTHER
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
researcher

Study Record Dates

First Submitted

March 5, 2020

First Posted

March 9, 2020

Study Start

March 20, 2019

Primary Completion

January 31, 2023

Study Completion

March 31, 2023

Last Updated

November 16, 2022

Record last verified: 2022-11

Locations

IT(1)