Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT02200276 |
| Other study ID # |
NA_00092365 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
March 2014 |
| Est. completion date |
June 2026 |
Study information
| Verified date |
March 2024 |
| Source |
Johns Hopkins University |
| Contact |
Engle Abrams |
| Phone |
410-550-2061 |
| Email |
eabrams3[@]jhmi.edu |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
The immune system is the part of the body that protects against infection. The immune system
often doesn't work as effectively as people get older. This research is being done to find
out how the immune systems in older people who are over age 75 respond to influenza vaccine
(flu shot). We also want to find out if chronic cytomegalovirus (CMV) infection, a common
virus infection in older persons affects the immune response in people older than 75 years of
age who receive a flu shot. The Flu Shot is a vaccine approved for the prevention of
influenza ("Flu") infections and is recommended every year for all persons 50 years and
older. People who are older than 75 years of age are considered healthy or frail may join. A
total of 1025 persons will be participating in this study.
In order to determine if you are qualified for the study, we would ask you to answer a few
questions over the phone that will take approximately 5 minutes. If you qualify and agree to
proceed, you will be asked to come to Johns Hopkins Bayview Medical Center or, if you are
unable to come to Bayview, one of our staff can visit you at your home. During that visit we
obtain consent, review your medical history, and measure your vital signs, walking speed and
grip strength. We will also administer a few brief questionnaires and collect urine and blood
samples. We will then give you the Influenza vaccine for free. 7 days post receiving your
Influenza Vaccine we will collect a small blood sample for further immune system testing.
also, you will be asked to complete a 12-question survey which will assess your symptoms over
the past 7 days (post receiving the Influenza vaccine). Also 4 weeks post receiving your
Influenza vaccine you will be asked to complete a third visit that will include follow up
health questionnaires and an influenza symptoms assessment questionnaire and vital signs. A
third blood draw will be collected (approximately 10 teaspoons) to measure immune responses
to the influenza vaccine. In addition, you will receive your test result (CBC/w/Diff.) from
visit #1. Throughout the influenza study season, we will call you once a week to ask about
your general health and any Flu-like symptoms. These calls will be made throughout the Flu
season which typically lasts through May. If you begin to have any influenza like symptoms at
any time during the study, we ask that you call our office to report these symptoms so that
we may perform vital signs, nasal swab to confirm influenza, and a fourth blood draw to look
at the immune response and protection of influenza vaccine.
Description:
Seasonal influenza causes significant morbidity and mortality and is the fourth leading cause
of death for older Americans. Annual immunization with a trivalent inactivated influenza
vaccine (TIV) is recommended for all adults 50 years and older. However, despite improved
vaccination coverage in older adults over time, influenza-related mortality has actually
increased. While many TIV studies indicate its benefit for older adults as a whole, these
studies lacked representation of the older and frail subset of the elderly who suffer over
three-quarters of influenza-related mortality. Our pilot study funded by a Beeson K23 award
showed significant vaccine failures in both antibody response to TIV and clinical protection
in the frail elderly. Our preliminary data also suggest that chronic cytomegalovirus (CMV)
infection as defined by the presence of CMV viral DNA in peripheral monocytes using a highly
sensitive and specific nested PCR-based assay developed in our laboratory, rather than
anti-CMV IgG serology, is associated with poor antibody and T-cell responses to TIV
immunization as well as poor clinical protection. This is likely because anti-CMV IgG
serology, the conventional diagnostic measure for chronic CMV infection, is a crude measure
that merely indicates prior exposure to CMV and does not distinguish chronic (persistent)
from past (resolved) infections. Mechanistically, precipitous immune functional decline has
been observed in those over 75 and chronic CMV infection may contribute significantly to
age-related immune senescent remodeling, termed immunosenescence. In order to improve our
assessment of the effectiveness of TIV immunization and understanding of risk factors and
underlying immune mechanisms that determine vaccine failure in adults over age 75, the frail,
oldest old adult subset, this study is designed to conduct prospective, 4-year TIV
immunization and post-vaccination influenza surveillance in adults over 75 years. We will
first assess chronic CMV infection defined by detectable CMV DNA in peripheral blood
monocytes and frailty status of the study participants and administer the Fluzone High-Dose
TIV vaccine. Influenza-like illness (ILI) cases will be identified through post-vaccination
influenza surveillance as previously done in the Beeson project and respiratory specimens
obtained from ILI cases will be tested using the cutting edge PCR-based IBIS assay which can
accurately subtype influenza and other respiratory viruses in the laboratory of Dr. Charlotte
Gaydos in Division of Infectious Disease, a co-investigator of this project. Strain-specific
antibody responses to TIV immunization will be measured by the standard hemogglutination
inhibition (HI) assay. We will also evaluate T-cell responses to influenza viruses at
baseline and after TIV immunization. Taken together, these studies will provide more accurate
assessment of the clinical effectiveness of TIV immunization in real world geriatric
population over age 75 and its underlying humoral and cell-mediated immune mechanisms.
Moreover, we investigate the role of chronic CMV infection as defined by the presence of CMV
viral DNA in peripheral monocytes as a risk factor for vaccine failure in the elderly over
age 75. Because this oldest old subset is growing most rapidly in numbers and is at greatest
risk for influenza-related morbidity and mortality. The long-term goal of this research is to
strengthen immune protection against influenza for vulnerable older Americans through more
effective and targeted immunization strategies as well as possibly through prevention and
mitigation of chronic CMV infection.
