Trial record 5 of 4737 for:    Open Studies | "Immune System"

Zoster Vaccine Response in the Frail Elderly

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2013 by McMaster University
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Mark Loeb, McMaster University
ClinicalTrials.gov Identifier:
NCT01328548
First received: March 15, 2011
Last updated: October 31, 2013
Last verified: October 2013
  Purpose

This study is being done to evaluate the zoster vaccine response in the nursing home elderly (80 years or older). As the immune system ages, the response to vaccines is not always as strong as in younger people. Previous zoster vaccine studies have excluded nursing home residents so the vaccine effect in this population is not known. Furthermore, the immune and genetic reasons as to why the vaccine works well in some people but not in others are also unknown. The goal of this study is to evaluate why some immune systems respond well to the vaccine and why others do not.


Condition
Immune System Diseases

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Prospective
Official Title: Immune and Genetic Correlates of Response to Zoster Vaccine in the Frail Elderly: a Pilot Study

Resource links provided by NLM:


Further study details as provided by McMaster University:

Primary Outcome Measures:
  • Change from Baseline in T-cell response to the VZV vaccine in the frail elderly [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
    As the primary phenotype, we will compare change in responder cell frequency (RCF) and Enzyme-linked immunosorbent spot (ELISPOT) from baseline (i.e., pre and post vaccination). A high baseline T cell response will be defined as RCF = >5.0 and ELISPOT = >50 spots and a low baseline response will be RCF = <1.0 and ELISPOT = <10 spots.

  • Assessment of immune parameters compatible with inflammaging: CD4+/CD8+ ratio [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Characterization of T-cell populations will be conducted on whole blood using multi-parametric flow cytometry prior to immunization to characterize the immunological function of circulating T-cells in each participant.

  • Assessment of immune parameters compatible with inflammaging: high CD8+CD28-CD45RA+ T cells [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Characterization of T-cell populations will be conducted on whole blood using multi-parametric flow cytometry prior to immunization to characterize the immunological function of circulating T-cells in each participant.

  • Assessment of immune parameters compatible with inflammaging: TEMRA Cells [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Characterization of T-cell populations will be conducted on whole blood using multi-parametric flow cytometry prior to immunization to characterize the immunological function of circulating T-cells in each participant.

  • Assessment of immune parameters compatible with inflammaging: high T regulatory cells [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Characterization of T-cell populations will be conducted on whole blood using multi-parametric flow cytometry prior to immunization to characterize the immunological function of circulating T-cells in each participant.

  • Testing 150 candidate immune response genes for SNP analysis [ Time Frame: Baseline ] [ Designated as safety issue: No ]

    These will include Toll-like receptors, cytokines, chemokines, chemokine receptors, interferons and interferon receptors.

    Toll-like receptors: TLR1-TLR9 Cytokines: ILI1A, ILI1B, IL1RN, IL4, IL5, IL12B, IL13, CSF2 Chemokines: CCL1-CCL3, CCL3L1, CCL4-CCL8, CCL11, CCL13, CCL15-CCL28, CXCL1-CXCL14, CXCL16, CX3CL1 Chemokine receptors: CCR1-CCR10, CXCR1-CXCR6, CX3CR1, XCR1-XCR2 Interferons: IFNA1-IFNA2, IFNA4-IFNA8, IFNA10, IFNA13, IFNA14, IFNA16-IFNA17, IFNA21, IFNB1, IFNB3, IFNG, IFNK, IFNW1 Interferon receptors: IFNAR1, IFNAR2, IFNGR1, IFNGR2



Biospecimen Retention:   Samples With DNA

Retained specimens include DNA and blood cells.


Estimated Enrollment: 250
Study Start Date: May 2011
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Groups/Cohorts
Nursing Home Elderly Cases
Non-ambulatory nursing home residents <= 80 years old will be vaccinated with the zoster vaccine and provide baseline and post-vaccination blood samples. We will assess differences in genotype frequencies between participants with high and low RCF and ELISPOT responses using a candidate gene approach with SNPs. A case will be considered failure to mount a high response.
Nursing Home Elderly Controls
Non-ambulatory nursing home residents <= 80 years old will be vaccinated with the zoster vaccine and provide baseline and post-vaccination blood samples. We will assess differences in genotype frequencies between participants with high and low RCF and ELISPOT responses using a candidate gene approach with SNPs. A control will be a participant who mounted an adequate response as defined in primary outcomes.
Community dwelling seniors
Community dwelling seniors ages 60-75 will be enrolled as a control group for the laboratory testing. They will be vaccinated and will provide pre- and post-vaccination blood. If nursing home residents do not show a response it is important to know that it is not a failure of the laboratory's measurement of immunogenicity.

Detailed Description:

Deleterious changes in immunity that occur with aging are known as immunosenescence. Such changes, particularly in adaptive immunity, may lead to an impaired vaccine response in the elderly. Characterizing the immune determinants and the genetic basis for vaccine response in the frail elderly is a practical approach to better our understanding of immunosenescence. Data on genetic determinants to immunization are sparse, furthermore, to the best of our knowledge, none exist in the elderly. In this pilot study, we propose studying the immune response to the herpes zoster vaccine and the underlying genetic determinants of the immune response in elderly residents of nursing homes.

The three specific aims of this study are to generate data in order to 1) assess the T-cell response to the varicella-zoster virus (VZV) vaccine in the frail elderly; 2) assess whether immune (T-cell) phenotypes are associated with a response; 3) test the association between immune response genotype sets and T-cell response. We hypothesize that response to the VZV vaccine in elderly nonambulatory nursing home residents is a function of characteristic T-cell immune phenotypes prior to vaccination and that there are immune genetic polymorphisms associated with the response. This study will allow us to generate preliminary data and establish feasibility in order to address these questions fully in a larger population in a subsequent grant application.

  Eligibility

Ages Eligible for Study:   80 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

Elderly, non-ambulatory residents of nursing homes.

Criteria

Inclusion Criteria:

  • nursing home resident
  • greater than or equal to 80 years old
  • non-ambulatory

Exclusion Criteria:

  • less than 80 years old
  • ambulatory
  • taking immunosuppressive medication
  • history of primary or acquired immuno-deficiency states including leukemia, other malignant neoplasms affecting the bone marrow or lymphatic system, and AIDS
  • active untreated tuberculosis
  • previous receipt of varicella vaccine
  • residents expected to expire within 30 days, in the opinion of the most responsible physician
  • residents planning to move nursing homes within the year
  • temporary residents
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01328548

Contacts
Contact: Sasha Eskandarian, MSc 905-525-9140 ext 26672 eskand@mcmaster.ca
Contact: Jennie Johnstone, MD 905-525-9140 ext 22726 johnsj48@mcmaster.ca

Locations
Canada, Ontario
Macassa Lodge Recruiting
Hamilton, Ontario, Canada
Contact: Cheryl Collins, RN       cheryl.collins@hamilton.ca   
Sponsors and Collaborators
McMaster University
Merck Sharp & Dohme Corp.
Investigators
Principal Investigator: Mark B. Loeb, FRCPC,MD,MSc McMaster University
  More Information

Publications:
Oxman MN. Clinical manifestations of herpes zoster. In: Arvin AM, Gershon AA, eds. Varicella zoster virus: virology and clinical management. Cambridge, England: Cambridge University Press, 2000:246-75.

Responsible Party: Mark Loeb, Professor, McMaster University
ClinicalTrials.gov Identifier: NCT01328548     History of Changes
Other Study ID Numbers: 09-450
Study First Received: March 15, 2011
Last Updated: October 31, 2013
Health Authority: Canada: Health Canada

Keywords provided by McMaster University:
varicella-zoster virus
vaccine
T-cell
genes
frail elderly
immunosenescence
immune and genetic correlates of response to zoster vaccine in the elderly

Additional relevant MeSH terms:
Immune System Diseases

ClinicalTrials.gov processed this record on September 30, 2014