Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Influenza Vaccine Responses as a Means of Assessing Immune Competence in Chimeric Kidney/Stem Cell Transplant Recipients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02623075
Recruitment Status : Active, not recruiting
First Posted : December 7, 2015
Last Update Posted : April 12, 2019
Sponsor:
Information provided by (Responsible Party):
Joseph Leventhal, Northwestern University

Tracking Information
First Submitted Date  ICMJE November 19, 2015
First Posted Date  ICMJE December 7, 2015
Last Update Posted Date April 12, 2019
Study Start Date  ICMJE October 2015
Estimated Primary Completion Date October 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 2, 2015)
Analysis of Immune Response in Transplant Recipient Blood Assays [ Time Frame: 1 year ]
To quantify the response to inactivated influenza vaccine, quadrivalent (IIV4), standard dose in up to 15 tolerance (chimeric) recipients compared to 15 matched, healthy controls and 15 matched, kidney transplant recipients on standard immunosuppression
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Influenza Vaccine Responses as a Means of Assessing Immune Competence in Chimeric Kidney/Stem Cell Transplant Recipients
Official Title  ICMJE Influenza Vaccine Responses as a Means of Assessing Immune Competence in Chimeric Kidney/Stem Cell Transplant Recipients
Brief Summary Influenza infection in solid organ transplant recipients is associated with increased morbidity and mortality compared to non-transplanted controls, due in part to the effects of immunosuppression which is necessary to prevent rejection of the transplanted organ. However, transplant patients are less likely to produce antibodies when vaccinated and when they do, the peak and duration of antibody responses are reduced compared to healthy controls. There are considerable differences in the magnitude of these responses, reflecting variability in individual responses to the influenza vaccine and to the immunosuppression regimen. The investigators hypothesize that chimeric kidney transplant recipients off of immunosuppression will have post vaccine immune responses that are comparable to age and gender matched healthy controls.
Detailed Description

Influenza infection in solid organ transplant recipients is associated with increased morbidity and mortality compared to non-transplanted controls, due in part to the effects of immunosuppression which is necessary to prevent rejection of the transplanted organ. Annual influenza vaccination is the best way to prevent influenza infection and current CDC, AST Infectious Diseases Community of Practice and American Society for Blood and Marrow Transplantation guidelines recommend annual influenza vaccination to all transplant recipients. However, transplant patients are less likely to produce antibodies when vaccinated and when they do, the peak and duration of antibody responses are reduced compared to healthy controls. There are considerable differences in the magnitude of these responses, reflecting variability in individual responses to the influenza vaccine and to the immunosuppression regimen.

Over the past several years, the investigators have conducted a Phase 2 clinical trial of combined kidney and stem cell transplantation that has been successful in achieving transplantation tolerance in a significant number of recipients. A central tenant for transplantation tolerance is a selective loss of immune reactivity to the allograft while preserving immune responses to all other antigens. The investigators hypothesize that chimeric kidney transplant recipients off of immunosuppression will have post vaccine immune responses that are comparable to age and gender matched healthy controls. The proposed studies aim to assess the immune competence in these fully chimeric tolerant recipients, by quantifying their T and B cell responses to the 2015-2016 inactivated influenza vaccine, quadrivalent (IIV4), standard dose and by testing whether the responding T and B cells arise from memory cells of recipient origin.

These studies will allow the investigators to quantify the influenza -specific cellular, humoral, and molecular responses to IIV4 in tolerant vs. matched controls. On days 0 and 30 days post -IIV4, the flu-specific B cell and neutralizing antibody responses, and the flu-specific IFN-gamma T cell response will be quantified. Additionally, the investigators will perform genome-wide gene expression profiling on isolated PBMC on days 0 and 30 post-IIV4 to characterize the blood response at the transcriptome level.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Influenza
Intervention  ICMJE Biological: Influenza vaccine
Blood samples will be collected at research study visits at 0 and 30 days (+/- 2 days) post-IIV4 (influenza vaccine). Collection will be as follows: 45-50 ml blood at each visit (not to exceed more than three visits over a two month period).
Other Name: Fluarix
Study Arms  ICMJE
  • Experimental: Transplant recipients (Chimeric)
    Adults who have received a kidney/stem cell transplant and have achieved chimerism will receive the IIV4 (influenza vaccine).
    Intervention: Biological: Influenza vaccine
  • Experimental: Transplant recipients (IS)
    Adults who have received a kidney/stem cell transplant and are currently maintained on standard immunosuppressive therapy will receive the IIV4 (influenza vaccine).
    Intervention: Biological: Influenza vaccine
  • Active Comparator: Controls
    Healthy adults who meet inclusion and exclusion criteria will receive the IIV4 (influenza vaccine).
    Intervention: Biological: Influenza vaccine
Publications * Not Provided

*   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 Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: December 2, 2015)
45
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE April 2020
Estimated Primary Completion Date October 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Adults who have received either a combined kidney/stem cell transplant and have achieved chimerism or post-transplant recipients who are maintained on standard immunosuppressive therapy. Additionally, healthy controls of either gender ≥ 18 years of age will also be recruited.
  • Subjects must be willing and able to receive the IIV4 and provide blood samples at research visits.
  • Subjects must be willing and able to read, understand, and be capable of giving informed consent for prospective enrollment.

Exclusion Criteria

  • Subjects less than 18 years of age.
  • Any condition that, in the opinion of the attending physician, would place the patient at undue risk by participating. Specific conditions include but are not limited to anemia prohibitive of phlebotomy, coagulopathy or inability to receive the IIV4.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 89 Years   (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 United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02623075
Other Study ID Numbers  ICMJE STU00201741
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Joseph Leventhal, Northwestern University
Study Sponsor  ICMJE Northwestern University
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Joseph Leventhal, MD, PhD Northwestern University
PRS Account Northwestern University
Verification Date April 2019

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