The main objective of this study is to investigate the effectiveness of the humeral immune response after influenza revaccination in patients with MG with acetylcholine antibodies (AChR MG). The secondary objectives are to determine if vaccination…
ID
Source
Brief title
Condition
- Neuromuscular disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Change in total influenza specific serum IgG titer in patients with AChR MG.
Secondary outcome
Clinical relevant change in clinical scores (2 points for MG-ADL, 3 points for
the QMG and the MG composite). Approaches to look at the clinic:
1. The mean change of the test scores of the two groups (A+B vs. C+ D)
2. The number of patients who show a clinical relevant test on one of the tests
en
compare this number of patients between the groups.
3. If a patient shows a clinical relevant change on a test, to look whether
this is also
on the other tests en compare this number of patients between the two groups
(A+B vs C+D).
- Change in autoimmune antibody titers against AChR.
- The effect of the pre-study medication (use of immunosuppressive medication)
at the immunological response.
Background summary
Myasthenia gravis (MG) is neuromuscular disorder in which functional
acetylcholine receptors (AChR) become depleted at neuromuscular junction due to
an antibody-mediated autoimmune attack on the neuromuscular synapse. Patients
are at an increased risk of infection due to the immunosuppressive therapy,
while at the same time vaccination might be less effective. Despite the common
use of immunosuppressive treatment in these patients, little is known about the
effectiveness and safety of vaccination in these patients. Recently a tetanus
revaccination study in MG patients showed an effective response to the booster
(unpublished data), without any major safety issues. We would like to further
study the effect of vaccinations on MG, using the yearly influenza vaccination.
Influenza is a frequently used vaccine with a well know safety profile in
healthy persons, but about the effectiveness and safety in myasthenic patients
little is known. Studying the influenza vaccine would give additional
information compared with the tetanus revaccination. This is because it is a
vaccine in which 2 of the 3 used strains are new influenza strains for the
patient this season. This in contrast with the tetanus vaccine, which is a
revaccination instead of a de novo vaccination.
Study objective
The main objective of this study is to investigate the effectiveness of the
humeral immune response after influenza revaccination in patients with MG with
acetylcholine antibodies (AChR MG). The secondary objectives are to determine
if vaccination induces immunological or clinical exacerbation in patients with
AChR MG.
Study design
The study is a longitudinal experimental study. Blood samples, clinical tests
and questionnaires will be used. The patient and the clinician who takes the
clinical tests are blinded till the end of the visit at 4 weeks. The MG-ADL at
2 and/or 3 months is open label follow-up.
Intervention
Influenza vaccine and/or placebo (NaCl 0.9%)
Study burden and risks
At the day of the vaccination (or placebo) 17.5 ml blood will be withdrawn and
the clinical tests will be taken. Four weeks after the revaccination again
17.5ml blood will be withdrawn and the clinical scores will be taken. If the
patient received the placebo at the first visit, they will receive the
influenza revaccination, to ensure that none of the patients that participate
in the study misses the active influenza immunization. In case that the patient
receives the influenza vaccine at the second visit, 17.5 ml blood will be
withdrawn 4 weeks after the real immunization. Side effects of the
revaccination include redness at the injection site, muscle ache and fever.
These will be recorded and monitored throughout the trial. The influenza
vaccine is frequently used en known for its safety. In theory the vaccine could
induce a worsening of the symptoms. However, this risk is considered very low
based on our experience with yearly flu vaccination and the tetanus
revaccination study in MG patients.
Albinusdreef 2
Leiden 2333ZA
NL
Albinusdreef 2
Leiden 2333ZA
NL
Listed location countries
Age
Inclusion criteria
1. Males and females aged above 18 years at the time of the injection.
2. Patient with ocular or generalized AChR MG and
3. A positive serologic test for AChR antibodies > 0.5 nmol/l in the past
4. Patient with prednisone dose lower than 30mg and stable (dose +/- 5mg) during the 3 months before participation; other immunosuppressive should be stable/unchanged.
5. A healthy control above 18 years at the time of injection with no immunosuppressive medication.
Exclusion criteria
1. MG patients with a severe form of MG (Grade 4 or 5 based on MGFA classification).
2. Myasthenic crisis in the last 3 months
3. Presence of a thymoma.
4. Planned thymectomy during the study period or within 12 months prior of the tetanus toxoid booster immunization.
5. Any confirmed or suspected immunosuppressive or immunodeficient condition not related to the treatment of MG, including human immunodeficiency virus (HIV) infection, or a family history of congenital or hereditary immunodeficiency.
6. History or evidence of administration of immunoglobulins within 3 months prior to the tetanus revaccination.
7. History or evidence of plasmapheresis within 3 months prior to the tetanus revaccination.
8. At high risk for aspiration.
9. Pulmonary: forced vital capacity reduced to less than 70% of predicted capacity.
10. History of allergic disease or reactions likely to be exacerbated by any component of the vaccine.
11. History of relevant chronic degenerative, psychiatric, or neurological disorder other than MG.
12. Severe hepatic, renal or cardiac insufficiency.
13. Major congenital defects or serious chronic illness other than MG.
14. Pregnancy or desire to become pregnant during the study.
15. Use of vitamin-K antagonist or new anti-coagulants (NOACS)
16. The patient is unable to fill out the study questionnaires or be interviewed in Dutch, or is unable to undergo the tests needed for the study, or is unable to give informed consent for participation in the study.
17. The investigator can exclude patients for this trial which are deemed not suitable for any reason.
Design
Recruitment
Medical products/devices used
metc-ldd@lumc.nl
metc-ldd@lumc.nl
Followed up by the following (possibly more current) registration
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Other (possibly less up-to-date) registrations in this register
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In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2016-003138-26-NL |
| CCMO | NL58746.058.16 |