This study will recruit an increasingly high-risk subset of adults 60 and older. All subjects will be vaccinated with the current preparation of the licensed inactivated influenza vaccine. Each year of the study, the following will be collected: antibody titers, cytokine levels, and other host reposnse proteins at pre- and post- vaccination time points, which will be compared to subjects who do and do not get the influenza illness.

Condition	Intervention
Influenza	Vaccine: Commerical TriValent Split Influenza Virus

Further Study Details: 

Expected Total Enrollment:  150

This study will increase our understanding of how age, congestive heart failure or a prior hospitalization for an influenza-related acute coronary event affects the immune response to influenza vaccination. By elucidating the defects in the immune response to influenza vaccination that are associated with the subsequent influenza illness, these methods can be used to screen subsets of older adults to establish the risk profile related to influenza in that population, to target these defects for future vaccine development and to use these methods as surrogates of protection to screen potential vaccines prior to conducting large scale clinical trials to establish clinical efficacy. The experimental design incorporates extensive experience in measuring T-cell responses to influenza vaccination and a study design that reflects an understanding of the variables that contribute to the heterogeneity of health in the older adults with heart disease. The study group will consist of 150 adults, age 60 years and older, characterized according to age, presence of congestive heart failure (CHF) (NYHA Class II-IV) or Ischemic heart disease (IHD), or (to be identified in the prior influenza season) an admission with an acute coronary syndromes (ACS) or exacerbation of CHF. All study participants will be vaccinated with the current preparation of licensed inactivated influenza vaccine by deltoid injection. In each year of the study, serum antibody titers, serum cytokine levels, ex vivo levels of IFN-gamma and IL-10, and ex vivo and in vitro levels of granzyme B (Grz B) in influenza-stimulated PBMC at the pre- and post-vaccination (4, 10 and 16 weeks) time points will be compared in subjects who do and do not get influenza illness. The peak as well as the duration of the response to vaccination for each of the immunologic measures will be determined. In each year of the study, the cut-off levels will be determined for antibody titers and ex vivo levels of IFN-gamma, IL-10 and Grz B activity using Receiver-Operator Curve analyses. From the previous data, differences between older adults with and without CHF are anticipated to be smaller than the difference between those who do and do not develop influenza illness. A 10% attack rate is anticipated in at least 3 of the 5 years. A case-control study design will determine differences between influenza to non-influenza controls. This study will be a subset of additional analyses of blood samples collected at the four scheduled visits pre-vaccination and 4, 10 and 16 weeks post-vaccination. PBMC collected at each time point are frozen until influenza cases are identified. Influenza cases will be compared to non-influenza age-matched controls for cytokine and Grz B levels in virus-activated (ex vivo) or virus-stimulated (in vitro) PBMC will be compared. Influenza cases associated with hospitalization for ACS or CHF will be compared to matched controls hospitalized with ACS or CHF. Data will include results of additional assays using varying culture conditions and fluorescence-activated cell sorter and microarray analyses. The potential benefits to subjects include free vaccination in the study. Subjects are also educated on how to recognize when they have an influenza illness, conservative measures for taking care of themselves during the illness and to see their primary care physicians for treatment options as influenza can be a more serious illness in older people.

Ages Eligible for Study:  20 Years and above,  Genders Eligible for Study:  Both

Accepts Healthy Volunteers

Criteria

Inclusion Criteria:

• Must be willing to be vaccinated with the current influenza vaccine
• ''''Healthy'''' older adult participants age 60 and older who may have underlying chronic diseases but no diagnosis of CHF
• High-risk older adults with cardiovascular disease age 60 and older and have a diagnosis of CHF or IHD including ACS
• Healthy young adults between the ages of 20 and 40 years

Exclusion Criteria:

High-risk older adults with cardiovascular disease: exclusion criteria are those with cardiovascular diseases due to intravenous drug abuse, myocarditis or congenital abnormalities.

Ambulatory older adults are "usual aging" persons age 60 years and older: Specific exclusions are congestive heart failure, advanced kidney disease (serum creatinine > 2 mg/dl), diabetes requiring insulin, immunosuppressive disorders or immunosuppressive agents including oral prednisone in doses >10 mg daily.

Healthy Young adults: must have no underlying chronic medical conditions (e.g., diabetes, kidney, autoimmune, cardiac or pulmonary) and no chronic use of immunosuppressive medications such as steroids.

• Allergic reactions to eggs or perservatives such as those contained in contact lens solutions
• A previous significant reaction to vaccination or if they refuse to receive influenza vaccination
• Known immunosuppressive disorders or medications (including oral prednisone in doses >10mg daily) or have not received influenza vaccination in the past
• Subjects who report respiratory illness within the two-week period prior to vacination
• Subjects reporting respiratory symptoms at the first study visit are re-scheduled to a time when they have not had a respiratory illness (at least two symptoms of cough, runny nose, malaise and fever) within the two-week period to vaccination
• Young adults with any underlying chronic diseases
• Cardiovascular diseases due to intravenous drug abuse, myocarditis or ocngenital abnormalities
• Healthy older adults with advanced kidney disease (serum creatinine >2mg/dl) or diabetes requiring insulin
• Any condition that in the opinion of the investigator would interfere with the interpretation or evaluation of the vaccine

Please refer to this study by ClinicalTrials.gov identifier  NCT00138398

Janet McElhaney      (757) 466-7040 

Connecticut
      University of Connecticut Health Center, Farmington,  Connecticut,  06030,  United States; Recruiting

Study ID Numbers:  05-0056
Last Updated:  August 29, 2005
Record first received:  August 26, 2005
ClinicalTrials.gov Identifier:  NCT00138398
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-08-30