Clinical trial NCT01687517: Efficacy and Safety of Influenza Vaccine During Sarcoidosis
Official title: Determination of the Efficacy and Safety of the Seasonal Influenza Vaccine Among Patients Suffering From Sarcoidosis.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Sarcoidosis
Influenza Vaccine
Keywords: sarcoidosis
healthy volunteers
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2012-09-19
Enrollment: 190
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Sarcoidosis is an inflammatory disease of unknown origin that can affect all organs, especially the lungs and mediastinum. Some location of sarcoidosis may require treatment with corticosteroids or immunosuppressors.Although seasonal influenza vaccination can be recommended in sarcoidosis in some subgroups at risk (respiratory failure, pulmonary fibrosis, age over 65, use of immunosuppressive therapy, etc ...), the investigators presently have no data on the efficacy and safety (absence of adverse reactions) of seasonal influenza vaccination in sarcoidosis.Especially it is not known whether the seasonal influenza vaccine provides the same rate and same type of vaccine response in sarcoidosis patients than in the general population. Similarly, it is unclear whether the vaccine response is modified by the severity of the disease and treatment with corticosteroids and immunosuppressors.Based on what is known in systemic lupus and rheumatoid arthritis, which are both inflammatory and autoimmune diseases, the investigators expect at best a 50% vaccine response in patients with sarcoidosis and a 85% vaccination response in healthy controls. The demonstration of a vaccine response could allow reconsidering new vaccine approaches in sarcoidosis.

Detailed description: Data on vaccination in sarcoidosis are largely insufficient. It is thus unclear whether the vaccine response is modified according to the clinical phenotype of the disease and/or treatment with corticosteroids and immunosuppressants. However, sarcoidosis is accompanied by numerous disturbances of the immune system, including a tendency to anergy which may affect the efficacy of the vaccine, especially when the disease is active and severe. In addition, the tolerance of influenza vaccination in patients with sarcoidosis has not been studied yet.The influenza vaccination in sarcoidosis is a common practice among medical specialists who care for patients with sarcoidosis, either internists or lung specialists.. However, the practice of this vaccination is not based on scientific evidence, because there are no data establishing the efficacy and safety of influenza vaccination in sarcoidosis.Thus, it is possible that the influenza vaccine is less immunogenic in patients with sarcoidosis than in healthy adults, which may reduce the clinical effectiveness of vaccination. It therefore seems essential to determine the efficacy and safety of this vaccine, which is widely practiced. Poor efficiency could lead to the development of different vaccination strategies, based in particular on the administration of adjuvanted vaccines.

Eligibility criteria: Inclusion Criteria for patients:

* Age ≥ 18 and ≤ 65;
* Signature of informed consent
* Follow-up : six months following the influenza vaccination at D0
* Sarcoidosis diagnosed and histologically proven since at least 6 months
* unchanged treatment of Sarcoidosis for at least 3 months, except for the case of a decrease in doses of corticosteroids and at a stable dose of immunosuppressive drugs
* Indication for a seasonal influenza vaccination.

Existence of one or more of these clinical situations:

* pulmonary location (dyspnea, radiological or stage IV pulmonary function tests (PFT) altered with decreased forced vital capacity (FVC), forced expiratory volume average (FEV) or the diffusion of carbon monoxide (TLCO) below 65% of predicted value;
* Cardiac impairment confirmed
* Central nervous system impairment and / or device and confirmed with clinical impact and abnormal imaging and / or electromyogram- Renal impairment (histologically confirmed) responsible for a decrease in creatinine clearance
* disabling Lupus pernio
* Sinuso-nasal and / or laryngeal impairment histologically confirmed
* Disseminated impairment, ie affecting more than four organs
* Dose of corticosteroids ≥to 10 mg per day of the equivalent of prednisone or the necessity of an immunosuppressive therapy (with the exception of Rituximab) to control sarcoidosis- Existence of an associated metabolic disorder
* Patients with sarcoidosis and living in a care house
* Sarcoidosis occurring in health/nursing staff

Inclusion criteria for healthy volunteers

* Age ≥ 18 and ≤ 65 years
* Signature of informed consent
* Lack of underlying disease, especially autoimmune diseases and / or sarcoidosis
* Follow-up possible during the six months following the influenza vaccination

Exclusion Criteria for all:

* Hypersensitivity to the active substances, eggs and one of the excipients of the vaccine
* Acute febrile episode in the week prior to vaccination
* Count with a documented case of influenza within a week prior to vaccination
* Infection with HIV HBV or HCV known,
* Current pregnancy or positive urine pregnancy test
* Multiple Sclerosis
* History of Guillain-Barré
* Organ Transplantation
* Cancer in the last 3 years
* Other vaccination received within 3 weeks prior to the study vaccine injection
* Treatment with chemotherapy
* Transfusion or immunoglobulin administration during the last 3 months
* Co-morbidity requiring biological therapy that specifically targets B cells (eg rituximab)
* Patient for which an increase of the treatment is planned in the month following vaccination.
* Acute infection in the month prior to vaccination
* non affiliated to a health social security system
* Participation in another biomedical research for the duration of the study
* Individuals deprived of freedom by an administrative or court order

Primary outcomes:
measure: Humoral immunogenicity
timeFrame: 21 days post-vaccination
Secondary outcomes:
measure: Immunogenicity
timeFrame: at Day 0, Day 21 and Day 180
measure: Clinical phenotype
timeFrame: at Day 21 and Day 180
measure: Auto immunity activity
timeFrame: At Day 0, at Day 21 and at 6 months post-vaccination
measure: Effect of therapy on immunogenicity
timeFrame: at Day 21 and Day 180
measure: Immunogenicity between groups
timeFrame: at Day 0, Day 21 and Day 180
measure: Long term immune response
timeFrame: At 6 months post-vaccination
measure: Lymphocytes subpopulations analysis
timeFrame: At Day 0 and at 21 days post-vaccination
measure: Regulatory T Lymphocytes
timeFrame: At Day 0 and Day 21
measure: Disease activity evolution
timeFrame: at Day 0, Day 21 and Day 180
measure: Other immune response
timeFrame: Between Day 0 to 6 months post-vaccination
Other outcomes:
Locations:
city: Paris
country: France
facility: Hotel-Dieu Hospital
Study officials:
affiliation: Hôtel Dieu Hospital
name: Claire Le Jeunne, MD, PhD
role: STUDY_CHAIR
References:
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citation: Statement on sarcoidosis. Joint Statement of the American Thoracic Society (ATS), the European Respiratory Society (ERS) and the World Association of Sarcoidosis and Other Granulomatous Disorders (WASOG) adopted by the ATS Board of Directors and by the ERS Executive Committee, February 1999. Am J Respir Crit Care Med. 1999 Aug;160(2):736-55. doi: 10.1164/ajrccm.160.2.ats4-99. No abstract available.
citation: Bouvry D, Naccache JM, Valeyre D. [Interstitial lung diseases in sarcoidosis]. Rev Prat. 2007 Dec 31;57(20):2258-65. French.
citation: Valeyre D, Duperron F. [Sarcoidosis: diagnosis and management of extra-pulmonary forms]. Rev Mal Respir. 2006 Dec;23(6):757-8. doi: 10.1016/s0761-8425(06)72092-7. No abstract available. French.
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citation: Asukata Y, Ishihara M, Hasumi Y, Nakamura S, Hayashi K, Ohno S, Mizuki N. Guidelines for the diagnosis of ocular sarcoidosis. Ocul Immunol Inflamm. 2008 May-Jun;16(3):77-81. doi: 10.1080/09273940802051100.