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Effect of Tocilizumab to the Cellular Immune Response to Influenza Vaccine

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ClinicalTrials.gov Identifier: NCT01980836
Recruitment Status : Unknown
Verified November 2013 by Tel-Aviv Sourasky Medical Center.
Recruitment status was:  Not yet recruiting
First Posted : November 11, 2013
Last Update Posted : November 11, 2013
Sponsor:
Information provided by (Responsible Party):
Tel-Aviv Sourasky Medical Center

Tracking Information
First Submitted Date  ICMJE November 4, 2013
First Posted Date  ICMJE November 11, 2013
Last Update Posted Date November 11, 2013
Study Start Date  ICMJE November 2013
Estimated Primary Completion Date February 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 4, 2013)
Cellular response [ Time Frame: 4 weeks ]
As described in the study design using the Interferin gamma and granzyme B levels
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: November 4, 2013)
Humoral response [ Time Frame: 4 weeks ]
Using an hemaglutination inhibition test as described in the study design
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Effect of Tocilizumab to the Cellular Immune Response to Influenza Vaccine
Official Title  ICMJE The Effect of Tocilizumab on the Cellular Immune Response to Seasonal Influnza Vaccine in Patients With Rheumatoid Arthritis
Brief Summary Patients with rheumatoid arthritis (RA) are prone to respiratory infections and therefore recommmended to receive vaccination against seasonal influenza. We and others have shown a relatively preserved humoral response to vaccination in RA patients. However, the cellular response as well as the effect of biologics such as tocilizumab on the cellular response has not been weel studied. The purpose of this study is the evaluate the effect of tocilizumab on the cellular immune response to influenza vaccine in patients with RA in comparison with healthy controls
Detailed Description

Inclusion criteria :

  • RA patients
  • Above the age of 18
  • Treated with tocilizumab at least 3 months

Exclusion criteria:

-egg allergy

Design of the study :

- Patients and controls will be vaccinated against sesaonal influenza. Blood will be taken the day of vaccination and 4 weeks after.

PBMC isolation The PBMCs will bere isolated from heparinized venous blood by density gradient centrifugation on Lymphoprep (Axis-Shield, Oslo, Norway) immediately after blood was drawn. The cells will be counted and suspended in RPMI 1640 supplemented with heat-inactivated 10% fetal calf serum, penicillin 100U/ml, streptomycin 0.1 mg/ml, and 2 mM L-glutamine (Biological Industries, Israel).

IFN-gamma secretion from PBMCs IFN-gamma secretion levels will be measured by ELISA in the supernatants of PBMCs that will be stimulated with either an influenza antigen mixture or with SEB, or left untreated.

Granzyme B activity assay The PBMCs will be cultured at 0.5 ml/well in 48-well plates (1.8X106 cells/well) and stimulated with an influenza antigen mix and SEB as described above. The cells will be lysed in lysis buffer (150mM NaCl, 15mM Tris, 1% Triton x100), then stored at

-760C. Granzyme B activity will be measured according to the protocol described by Gijzen et al. [13]. Briefly, frozen cell lysates will be subjected to three freeze/thaw cycles to enable the release of Granzyme B. Recombinant Granzyme B standards (Enzo Life Sciences International, Inc., PA) and cell lysates will be added in duplicate to a 96-well plate (20 µl/well). The reaction will start upon the addition of 80 μl of substrate solution containing 400 μM of Ac-IEPD-pNA substrate (Calbiochem, Darmstadt, Germany) in assay buffer (100mM HEPES pH 7.5, 10% (w/v), sucrose, 0.1% (w/v) CHAPS, and 10 mM DTT (Sigma Aldrich, Rehovot, Israel). The plate will be sealed, covered and incubated in a dark humidified chamber at 370C for 20 h. After incubation, the plate will be read at 405 nm. Granzyme B units will be calculated using a 4th order polynominal curve with a log (concentration)−log (absorbance) plot, and corrected for protein concentrations by the BCA protein assay (Thermo Scientific, IL).

The humoral response The antibody response will be measured by the HI test according to a standard WHO procedure as previously described [14]. The titer of an antiserum not showing any inhibition will be recorded as 1/10. Humoral response is defined as either a fourfold or greater rise in the titer of HI antibodies, or a rise from a non-protective baseline level (<1/40) to 1/40). Geometric mean titers of antibodies wull be calculated to assess the immunity of the whole group.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Condition  ICMJE
  • Rheumatoid Arthritis
  • Cellular Immune Response
Intervention  ICMJE Biological: Seasonal influenza vaccine
Study Arms  ICMJE
  • Active Comparator: Seasonal influenza vaccine in tocilizumab treated RA patients
    RA patients treated with tocilizumab
    Intervention: Biological: Seasonal influenza vaccine
  • Active Comparator: Seasonal influenza vaccine to Healthy controls
    Healthy controls will be vaccinated against seasonal influenza
    Intervention: Biological: Seasonal influenza vaccine
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: November 4, 2013)
40
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE February 2014
Estimated Primary Completion Date February 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Rheumatoid Arthritis patients treated with Tocilizumab for at least 3 months
  • Above the age of 18

Exclusion Criteria:

  • Allergy to eggs
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Israel
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01980836
Other Study ID Numbers  ICMJE TASMC-13-OE-245-CTIL
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Tel-Aviv Sourasky Medical Center
Study Sponsor  ICMJE Tel-Aviv Sourasky Medical Center
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Tel-Aviv Sourasky Medical Center
Verification Date November 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP