Intradermal Influenza Vaccine Study in Elders - Full Text View

Sponsors and Collaborators:	Program for Appropriate Technology in Health Puget Sound Veterans Administration Health Care System Seattle Institute for Biomedical and Clinical Research (SIBCR)
Information provided by:	Program for Appropriate Technology in Health
ClinicalTrials.gov Identifier:	NCT00504231

Purpose

The purpose of this study is to gain information on whether seniors could benefit from intradermal (ID) injection of influenza vaccine (giving the flu shot into the skin). We will compare different doses, injection methods, and evaluate the safety and side effects. Intradermal injection may potentially be better than the current practice of intramuscular (IM) injection (giving the flu shot into the muscle). The skin contains many dendritic cells which deliver antigens to immune cells to mount an immune response. Intradermal injections of lower than standard doses of vaccine have been shown to be generate immunity in younger, healthy adults, and in one study that included older healthy adults. This alternative method of giving reduced dose of influenza vaccine by ID injection could have profound impact, by increasing individual protection and/or allowing more people to receive the benefit of vaccination during periods of influenza vaccine shortage. We will also look at the response to the vaccine at the cellular level in a subset of individuals.

Condition	Intervention	Phase
Influenza	Biological: Fluzone Influenza Vaccine (2007-2008)	Phase II

MedlinePlus related topics: Flu

Drug Information available for: Influenza Vaccines Fluvirin

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Prevention, Randomized, Open Label, Dose Comparison, Parallel Assignment, Safety/Efficacy Study
Official Title:	Intradermal vs. Intramuscular Delivery of Influenza Vaccine in Immunocompetent Elders

Further study details as provided by Program for Appropriate Technology in Health:

Primary Outcome Measures:

Non-inferiority of seroconversion (HAI antibody titer >/= 1:32) between a reduced dose (0.3 ml) influenza vaccine delivered intradermally and a full dose (0.5 ml) delivered intramuscularly 1 month after vaccination. [ Time Frame: 1 month ]

Secondary Outcome Measures:

To compare HAI antibody titers between the group receiving a reduced dose (0.3 ml) influenza vaccine delivered intradermally and the group receiving a reduced dose (0.3 ml) delivered intramuscularly one month after vaccination. [ Time Frame: 1 month ]
To evaluate and compare the reactogenicity of influenza vaccine at reduced dose given intradermally as compared to reduced and full dose given intramuscularly. [ Time Frame: 1 month ]
To compare the reactogenicity and efficacy of giving reduced dose (0.3 ml) in 2 split volume injections (0.15 ml each), as compared to a single reduced dose (0.3 ml) given intradermally. [ Time Frame: 1 month ]
To compare HAI antibody titers one month after standard full dose intramuscular injection of influenza vaccine preceded one month prior by either reduced dose intradermal or intramuscular injection of influenza vaccine. [ Time Frame: 1 month ]
To compare cellular immune response to influenza vaccine delivered in a reduced dose intradermally or intramuscularly, or full dose delivered intramuscularly. [ Time Frame: 1 month ]

Estimated Enrollment:	300
Study Start Date:	September 2007
Study Completion Date:	January 2008
Primary Completion Date:	January 2008 (Final data collection date for primary outcome measure)

Intervention Details:

Manufactured by Sanofi Pasteur

Detailed Description:

Influenza virus causes yearly epidemics of respiratory disease, and is the leading cause of vaccine-preventable mortality in the United States. Persons over the age of 70 years account for greater than 90 percent of influenza-related deaths. Vaccine efficacy depends on host response and the match between circulating influenza strain and manufactured vaccine antigens. The only randomized controlled trial of influenza vaccine use in the elderly, using lab-confirmed influenza outcome, showed only 50% efficacy.1 Many elders remain at risk for disease and complications despite vaccination. Recent epidemics and experiences with vaccine shortages further highlight the need for strategies to improve influenza vaccine efficacy in the elderly and maximize the benefit of a limited vaccine supply.

Intradermal (ID) administration of influenza vaccine shows promise as an alternative to intramuscular (IM) injection, the current standard of care. Intradermal injection may more reliably deliver antigens to immune cells, as the skin contains large numbers of dendritic cells which are the most potent antigen-presenting cells for eliciting primary immune response. Dendritic cells in the skin may be involved in both humoral and cellular responses.

We hypothesize that in older individuals, a reduced dose of influenza vaccine given by the ID route may achieve the same degree of protection as a full dose given by IM route; and a reduced dose given by the ID route may achieve greater protection than a reduced dose given by IM route, as determined by the standard measure of immunogenicity, the serum hemagglutination inhibition (HAI) antibody titer 1 month following vaccination.

We propose to conduct a Phase II randomized controlled trial to assess the safety and immunogenicity of intradermal (ID) delivery of licensed inactivated trivalent influenza vaccine of varying dosages in immunocompetent elders age 65 and over. The safety and immunogenicity of ID injection will be compared to IM delivery of influenza vaccine. In addition, we will compare the cellular immune response of ID injection to IM delivery of the vaccine in a subset of 30 individuals.

This proposed study addresses a critical area of investigation both to improve annual influenza prevention and to prepare for pandemic influenza. In times of vaccine shortage, whether in interpandemic or pandemic periods, knowing if reduced doses of influenza vaccine can be given intradermally with the same immunologic effect as higher doses of vaccine given in the usual manner will allow health care providers to maximize the available influenza vaccine. Furthermore, improved vaccine effectiveness may decrease adverse health consequences of influenza in the elderly population.

Eligibility

Ages Eligible for Study:	65 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

Ambulatory, medically stable persons 65 years of age or older
Able to read and understand informed consent
Available during the trial period and for follow-up
Able to understand and comply with planned study procedures
Able to be contacted by telephone for follow-up of adverse events

Exclusion Criteria:

Known allergy to eggs or other components of vaccine (i.e., thimerosal)
History of Guillain-Barré Syndrome (GBS)
Has a confirmed or suspected immunodeficient or immunosuppressive condition (including congenital or acquired immunosuppressive therapy, and human immunodeficiency virus [HIV])
End-stage renal disease requiring hemodialysis
Active neoplastic disease or history of any hematologic malignancy (except localized skin or prostate cancer that is stable in the absence of therapy)
Acute or chronic condition that (in the opinion of the investigator) would render vaccination unsafe or would interfere with the evaluation of responses (including but not limited to the following: known chronic liver disease, significant renal disease, oxygen-dependent chronic lung disease, New York Heart Association Functional Class III or IV, unstable or progressive neurologic disorder, insulin controlled diabetes mellitus)
Use of experimental vaccines within the month prior to study entry, or expected use of experimental or licensed vaccines or blood/blood products during the duration of the study.
Receipt of immunoglobulin or other blood product within 3 months prior to enrollment
Receipt of other licensed vaccines within the preceding 4 weeks
History of a severe reaction following influenza vaccination
Current or planned participation in a research study of an investigational drug. Participation in research studies that involve use of licensed drugs, for either approved or investigational indications, will be permitted with the approval of the PI, as will participation in research studies that do not involve vaccines or medications.
Current use or previous chronic administration, defined as >14 days during the previous six months, of immunosuppressants or other immune-modifying drugs. (For oral or injected corticosteroids, the immune-modifying dose is defined as prednisone or its equivalent >10 mg/day or >800mcg per day of inhaled beclomethasone dipropionate or equivalent ). Topical steroids are allowed.
Use of cytotoxic therapy in the previous 2 years.
Plans to receive cytotoxic therapy during the study period.
Concurrent moderate to severe illness. Need to defer vaccination until recovery. (Vaccination is not contraindicated in subjects with mild illnesses or with low-grade fever).

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00504231

Sponsors and Collaborators

Program for Appropriate Technology in Health

Puget Sound Veterans Administration Health Care System

Seattle Institute for Biomedical and Clinical Research (SIBCR)

Investigators

Principal Investigator:	Ru-Chien Chi, MD	VAPSHCS
Principal Investigator:	Kathy Neuzil, MD	Program for Appropriate Technology in Health

More Information

Study ID Numbers:	ID/RD01
Study First Received:	July 12, 2007
Last Updated:	May 5, 2008
ClinicalTrials.gov Identifier:	NCT00504231
Health Authority:	United States: Food and Drug Administration

Keywords provided by Program for Appropriate Technology in Health:

influenza
prevention
intradermal

vaccine
delivery
elderly

Study placed in the following topic categories:

Virus Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Influenza, Human
Orthomyxoviridae Infections

Additional relevant MeSH terms:

RNA Virus Infections

ClinicalTrials.gov processed this record on January 16, 2009