Back to results

Efficacy and Safety of Influenza Vaccine During Sarcoidosis (SARCOVAC)

Primary Purpose

Sarcoidosis, Influenza Vaccine

Status

Completed

Phase

Phase 3

Locations

France

Study Type

Interventional

Intervention

Seasonal influenza vaccine available for the 2012-2013 vaccine campaign

About this trial

This is an interventional treatment trial for Sarcoidosis focused on measuring sarcoidosis, healthy volunteers

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

Hotel-Dieu Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Patient

Volunteer

Arm Description

90 patients suffering from sarcoidosis

100 volunteers

Outcomes

Primary Outcome Measures

Humoral immunogenicity

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

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

Descriptive study of the evolution of clinical phenotype (eg, severity of illness) after vaccination at D21 and D180

Auto immunity activity

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

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

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

Comparison of the persistence of the immune response between patients with sarcoidosis and control subjects at D180

Lymphocytes subpopulations analysis

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

Effect of the regulatory T cells titers on the seroconversion and seroprotection rates, and the seroconversion factor at D0

Disease activity evolution

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

Seroprevalence and comparison between D0 and D180 of anti-diphtheria toxin and anti-tetanus toxin in all individuals included.

Full Information

NCT ID

NCT01687517

First Posted

September 14, 2012

Last Updated

April 20, 2015

Sponsor

Assistance Publique - Hôpitaux de Paris

1. Study Identification

Unique Protocol Identification Number

NCT01687517

Brief Title

Efficacy and Safety of Influenza Vaccine During Sarcoidosis

Acronym

SARCOVAC

Official Title

Determination of the Efficacy and Safety of the Seasonal Influenza Vaccine Among Patients Suffering From Sarcoidosis.

Study Type

Interventional

2. Study Status

Record Verification Date

April 2015

Overall Recruitment Status

Completed

Study Start Date

October 2012 (undefined)

Primary Completion Date

June 2013 (Actual)

Study Completion Date

October 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Assistance Publique - Hôpitaux de Paris

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Sarcoidosis, Influenza Vaccine

Keywords

sarcoidosis, healthy volunteers

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

190 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Patient

Arm Type

Experimental

Arm Description

90 patients suffering from sarcoidosis

Arm Title

Volunteer

Arm Type

Active Comparator

Arm Description

100 volunteers

Intervention Type

Drug

Intervention Name(s)

Seasonal influenza vaccine available for the 2012-2013 vaccine campaign

Intervention Description

Single injection of the vaccine at D0 (0.5mL intra-muscularly or subcutaneous for patient under anticoagulant treatment)

Primary Outcome Measure Information:

Title

Humoral immunogenicity

Description

Time Frame

21 days post-vaccination

Secondary Outcome Measure Information:

Title

Immunogenicity

Description

Effect of the initial clinical phenotype (including disease activity score) on the seroconversion and seroprotection rates, and the seroconversion factor, at each visit

Time Frame

at Day 0, Day 21 and Day 180

Title

Clinical phenotype

Description

Descriptive study of the evolution of clinical phenotype (eg, severity of illness) after vaccination at D21 and D180

Time Frame

at Day 21 and Day 180

Title

Auto immunity activity

Description

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.

Time Frame

At Day 0, at Day 21 and at 6 months post-vaccination

Title

Effect of therapy on immunogenicity

Description

Effect of the dose of corticosteroids and immunosuppressive therapy on the seroconversion and seroprotection rates and seroconversion factor at D21 and D180;

Time Frame

at Day 21 and Day 180

Title

Immunogenicity between groups

Description

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.

Time Frame

at Day 0, Day 21 and Day 180

Title

Long term immune response

Description

Comparison of the persistence of the immune response between patients with sarcoidosis and control subjects at D180

Time Frame

At 6 months post-vaccination

Title

Lymphocytes subpopulations analysis

Description

Time Frame

At Day 0 and at 21 days post-vaccination

Title

Regulatory T Lymphocytes

Description

Effect of the regulatory T cells titers on the seroconversion and seroprotection rates, and the seroconversion factor at D0

Time Frame

At Day 0 and Day 21

Title

Disease activity evolution

Description

Time Frame

at Day 0, Day 21 and Day 180

Title

Other immune response

Description

Seroprevalence and comparison between D0 and D180 of anti-diphtheria toxin and anti-tetanus toxin in all individuals included.

Time Frame

Between Day 0 to 6 months post-vaccination

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Claire Le Jeunne, MD, PhD

Organizational Affiliation

Hôtel Dieu Hospital

Official's Role

Study Chair

Facility Information:

Facility Name

Hotel-Dieu Hospital

City

Paris

ZIP/Postal Code

75004

Country

France

12. IPD Sharing Statement

Citations:

PubMed Identifier

11070460

Citation

Mert A, Bilir M, Ozaras R, Tabak F, Karayel T, Senturk H. Results of hepatitis B vaccination in sarcoidosis. Respiration. 2000;67(5):543-5. doi: 10.1159/000067471.

Results Reference

background

PubMed Identifier

9787645

Citation

Recommendation for the composition of influenza virus vaccines for use in 1999. Wkly Epidemiol Rec. 1998 Oct 2;73(40):305-8. No abstract available. English, French.

Results Reference

background

PubMed Identifier

10430755

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.

Results Reference

background

PubMed Identifier

18320746

Citation

Bouvry D, Naccache JM, Valeyre D. [Interstitial lung diseases in sarcoidosis]. Rev Prat. 2007 Dec 31;57(20):2258-65. French.

Results Reference

background

PubMed Identifier

17886354

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.

Results Reference

background

PubMed Identifier

5183631

Citation

Lofgren S. The concept of erythema nodosum revised. Scand J Respir Dis. 1967;48(3):348-53. No abstract available.

Results Reference

background

PubMed Identifier

1301972

Citation

James DG. Lupus pernio. Lupus. 1992 May;1(3):129-31. doi: 10.1177/096120339200100302.

Results Reference

background

PubMed Identifier

18569792

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.

Results Reference

background

Learn more about this trial

Efficacy and Safety of Influenza Vaccine During Sarcoidosis

We'll reach out to this number within 24 hrs