Efficacy and Safety of Influenza Vaccine During Sarcoidosis (SARCOVAC)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT01687517
First received: September 14, 2012
Last updated: January 2, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention Phase
Sarcoidosis
Influenza Vaccine
Drug: Seasonal influenza vaccine available for the 2012-2013 vaccine campaign
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Determination of the Efficacy and Safety of the Seasonal Influenza Vaccine Among Patients Suffering From Sarcoidosis.

Resource links provided by NLM:


Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:
  • Humoral immunogenicity [ Time Frame: 21 days post-vaccination ] [ Designated as safety issue: No ]
    Humoral immunogenicity of the vaccine will be measured 3 weeks after injection of influenza vaccine (day 21) by comparison of the seroconversion rates between patients with sarcoidosis and the control group of healthy subjects.


Secondary Outcome Measures:
  • Immunogenicity [ Time Frame: at Day 0, Day 21 and Day 180 ] [ Designated as safety issue: Yes ]
    Effect of the initial clinical phenotype (including disease activity score) on the seroconversion and seroprotection rates, and the seroconversion factor, at each visit

  • Clinical phenotype [ Time Frame: at Day 21 and Day 180 ] [ Designated as safety issue: Yes ]
    Descriptive study of the evolution of clinical phenotype (eg, severity of illness) after vaccination at D21 and D180

  • Auto immunity activity [ Time Frame: At Day 0, at Day 21 and at 6 months post-vaccination ] [ Designated as safety issue: Yes ]
    Comparison of autoantibody levels before and after vaccination (anti-nuclear total, rheumatoid factor, anti-GM1 measured at D0, D21 and D180) in all individuals included in the study.

  • Effect of therapy on immunogenicity [ Time Frame: at Day 21 and Day 180 ] [ Designated as safety issue: No ]
    Effect of the dose of corticosteroids and immunosuppressive therapy on the seroconversion and seroprotection rates and seroconversion factor at D21 and D180;

  • Immunogenicity between groups [ Time Frame: at Day 0, Day 21 and Day 180 ] [ Designated as safety issue: No ]
    Comparison of the seroprotection rate and the seroconversion factor between patients with sarcoidosis and the control group of healthy subjects at D21 and D180 post-vaccination.

  • Long term immune response [ Time Frame: At 6 months post-vaccination ] [ Designated as safety issue: No ]
    Comparison of the persistence of the immune response between patients with sarcoidosis and control subjects at D180

  • Lymphocytes subpopulations analysis [ Time Frame: At Day 0 and at 21 days post-vaccination ] [ Designated as safety issue: No ]
    Comparison between D0 and D21 of the distributions in absolute values and percentages of circulating lymphocyte subpopulations, in particular mucosal "homing" CD4+ lymphocytes, in all individuals included in the study;

  • Regulatory T Lymphocytes [ Time Frame: At Day 0 and Day 21 ] [ Designated as safety issue: No ]
    Effect of the regulatory T cells titers on the seroconversion and seroprotection rates, and the seroconversion factor at D0

  • Disease activity evolution [ Time Frame: at Day 0, Day 21 and Day 180 ] [ Designated as safety issue: Yes ]
    Effect of the CD4+-CD103+ T cells + at J0 and its evolution between J0 and J21 days based on the scalability of sarcoidosis evaluated by 1/changes in serum enzyme angiotensin converting, IgG, IgA IgM,; 2/ the comparative pulmonary radiological changes and 3/ the in pulmonary function changes between day 0 and day 180.

  • Other immune response [ Time Frame: Between Day 0 to 6 months post-vaccination ] [ Designated as safety issue: No ]
    Seroprevalence and comparison between D0 and D180 of anti-diphtheria toxin and anti-tetanus toxin in all individuals included.


Enrollment: 190
Study Start Date: October 2012
Estimated Study Completion Date: March 2014
Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Patient
90 patients suffering from sarcoidosis
Drug: Seasonal influenza vaccine available for the 2012-2013 vaccine campaign
Single injection of the vaccine at D0 (0.5mL intra-muscularly or subcutaneous for patient under anticoagulant treatment)
Active Comparator: Volunteer
100 volunteers
Drug: Seasonal influenza vaccine available for the 2012-2013 vaccine campaign
Single injection of the vaccine at D0 (0.5mL intra-muscularly or subcutaneous for patient under anticoagulant treatment)

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

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01687517

Locations
France
Hotel-Dieu Hospital
Paris, France, 75004
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Investigators
Study Chair: Claire Le Jeunne, MD, PhD Hôtel Dieu Hospital
  More Information

Publications:
Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT01687517     History of Changes
Other Study ID Numbers: P110115
Study First Received: September 14, 2012
Last Updated: January 2, 2014
Health Authority: France: Ministry of Health

Keywords provided by Assistance Publique - Hôpitaux de Paris:
sarcoidosis
healthy volunteers

Additional relevant MeSH terms:
Influenza, Human
Sarcoidosis
Orthomyxoviridae Infections
RNA Virus Infections
Virus Diseases
Respiratory Tract Infections
Respiratory Tract Diseases
Lymphoproliferative Disorders
Lymphatic Diseases

ClinicalTrials.gov processed this record on August 28, 2014