Clinical trial NCT02511002: Long-term Observation of Hemagglutinin and Neuraminidase Inhibition Antibody Titers After Influenza Challenge
Official title: Long-Term Observation of Hemagglutinin and Neuraminidase Inhibition Antibody Titers After Influenza Challenge
Study type: OBSERVATIONAL
Overall status: ENROLLING_BY_INVITATION
Conditions: Post Influenza
Keywords: Natural History
Longitudinal Observation
Influenza Like Infection (ILI)
Immunity
Flu
Lead sponsor: National Institutes of Health Clinical Center (CC)
Sponsor class: NIH
First posted: 2015-07-29
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Healthy volunteers after influenza challenge and patients after natural influenza infection

Brief summary: Background:

- Influenza is a common viral infection, but it can be deadly for some people. Researchers want to learn more about how the body fights this virus. They want to study this in people who have recently been infected with influenza. They hope this can help them create more effective influenza vaccines.

Objective:

- To learn about long-term changes in the body s immune system after influenza infection.

Eligibility:

- People who have completed a previous LID Clinical Studies Unit influenza challenge study or current or prior participation in an LID natural history study and are willing to have samples stored for future research.

Design:

* Eligible participants will be asked to visit the clinic every 3 months for 2 years.
* During each visit, participants will have blood drawn from an arm vein using a needle and a syringe and a nasal sample.
* Participants will have a medical history and physical exam and vital signs performed. This will include blood pressure, heart rate, breathing rate, temperature, weight, and finger-measured blood oxygen. They will answer questions about any medicines taken and possible recent illnesses.
* If participants have symptoms of influenza, they may have an additional sample taken from the nose.
* Participants will complete a health questionnaire once a month on a secure website. Participants may also give their responses over the telephone.

Detailed description: Circulating anti-influenza antibodies are an important factor in predicting clinical illness and severity in those infected with influenza. Specific antibodies against influenza include proteins targeting hemagglutinin (HA) and neuraminidase (NA). Lifelong immunity does not occur with influenza, either from natural infection or from vaccination. Due to the antigenic variation of Influenza A, individuals may become infected multiple times with the same subtype of influenza and even with the same strain. In the setting of natural infection and vaccination, antibody titer levels can persist initially, but then wane over time.

In our previous challenge studies, measurements of antibody responses have been focused solely on the acute infection period up to 2 months after initial infection. Long-term changes in immunity have not been investigated. The challenge setting gives us the unique ability to follow individuals from a specific, known and well-characterized exposure/illness to measure long-term changes in antibody titers from a pre-exposure baseline. This study could offer unique insight into how anti-influenza antibody titers change over time naturally and in response to other infections and life events. This type of controlled study has never been done and we believe monitoring titers long-term will help us better understand protective correlates of influenza.

In this natural history study, we will follow individuals who have undergone influenza challenge or have been naturally infected with influenza to evaluate changes in anti-influenza antibody titers over a 2-year period. Subjects will be followed for symptoms of influenza-like illness (ILI) and other changes in clinical status through quarterly clinical evaluations with blood draws. Monthly questionnaires will be used to follow subjects in between visits.

Eligibility criteria: * INCLUSION CRITERIA:

  1. Completion of participation in an LID Clinical Studies Unit influenza challenge study or current or prior participation in an LID natural history study.
  2. Willing to have samples stored for future research.

CO-ENROLLMENT GUIDELINES:

Participants may be co-enrolled in other research studies. This will be addressed on a case-by-case basis with the approval of the principal investigator (PI) or associate investigator.

If a participant enrolls in another influenza challenge study, the participant will be removed from this study. The participant can re-enroll in this study after completion of the influenza challenge study and will be followed for two years following completion of the most recent influenza challenge study.

EXCLUSION CRITERIA:

Any condition or event that, in the PI s opinion, may substantially increase the risk associated with study participation or compromise the study s scientific objectives. Conditions that exclude a subject are considered to be unlikely, but an example would include a newly diagnosed medical condition that may alter a participant s immune system and make it unsafe to obtain scheduled blood samples for research purposes.

Primary outcomes:
measure: To characterize the timing of peak antibody response to hemagglutinin (HA) and neuraminidase (NA) post influenza challenge or after natural infection To evaluate the long-term variability of hemagglutinin inhibition (HAI) and neuraminidase inhib...
timeFrame: 2 years
Secondary outcomes:
measure: To correlate changes in clinical status such as influenza-like illness (ILI) or vaccinations with changes in antibody titers and other immune measures
timeFrame: 2 years
Other outcomes:
Locations:
city: Bethesda
country: United States
facility: National Institutes of Health Clinical Center
state: Maryland
Study officials:
affiliation: National Institute of Allergy and Infectious Diseases (NIAID)
name: Alison Han, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Grohskopf LA, Olsen SJ, Sokolow LZ, Bresee JS, Cox NJ, Broder KR, Karron RA, Walter EB; Centers for Disease Control and Prevention. Prevention and control of seasonal influenza with vaccines: recommendations of the Advisory Committee on Immunization Practices (ACIP) -- United States, 2014-15 influenza season. MMWR Morb Mortal Wkly Rep. 2014 Aug 15;63(32):691-7.
citation: Thompson WW, Weintraub E, Dhankhar P, Cheng PY, Brammer L, Meltzer MI, Bresee JS, Shay DK. Estimates of US influenza-associated deaths made using four different methods. Influenza Other Respir Viruses. 2009 Jan;3(1):37-49. doi: 10.1111/j.1750-2659.2009.00073.x.
citation: Cox RJ. Correlates of protection to influenza virus, where do we go from here? Hum Vaccin Immunother. 2013 Feb;9(2):405-8. doi: 10.4161/hv.22908. Epub 2013 Jan 4.