Influenza A H3N2 Human Challenge Study in Healthy Adult Volunteers
- Conditions
- Determine Minimally to Moderately Infective Dose (MMID) of Influenza A H3N2
- Interventions
- Other: Live recombinantly derived A/Bethesda/MM1/H3N2 virus
- Registration Number
- NCT02594189
- Brief Summary
Background:
Influenza A H3N2 is a flu virus. Symptoms include fever, cough, and runny nose. It can also be more serious. Researchers want to know more about how influenza causes disease in people. They hope to develop new vaccines and treatments for flu infection.
Objective:
To find the smallest amount of Influenza A H3N2 virus that causes a mild to moderate flu infection in healthy people. Also, to study the body s immune response to this virus and how the infection develops.
Eligibility:
Healthy people ages 18 50 who are:
Non-smokers or non-habitual smokers
Willing to not smoke for at least 9 days
Design:
Participants will be screened under NIAID protocol #11-I-0183
Participants will stay at an isolation unit at the clinic for at least 9 days. They will remain in the isolation unit except for study-specific activities.
The influenza virus will be sprayed into the nose.
Participants will be monitored 24 hours a day. They will have tests, including:
Medical history
Physical exam
Daily questionnaires about symptoms
Blood and urine tests
Nasal wash and swab: A small tube of salt water is placed in the nose to wash it. It then collects the
fluid. Or the inside of the nose is rubbed with a swab.
ECG: Measures the heart s electrical signals
ECHO: Sound waves take pictures of the heart
PFTs/Spirometry: They will blow into a machine that measures the air they blow.
Participants will be discharged after they test negative for influenza A.
Participants will return to the clinic for 4 follow-up visits over 8 weeks. They may complete questionnaires at home.
- Detailed Description
The high morbidity and mortality associated with both pandemic and seasonal influenza, and the anticipation of future influenza pandemics, puts influenza front and center in infectious disease research. Because the natural history and pathogenesis of human influenza has not been well characterized and cannot be adequately studied in animal models or with current in vitro techniques, important questions about influenza pathogenesis can only be approached through human challenge studies.
Although studies of influenza in healthy volunteers have played an important role in addressing aspects of the natural history of influenza disease and developing novel antivirals, prior to recently these important studies had not been performed in the US in over a decade. The H1N1 challenge studies we have performed since 2012 have sought to improve upon the studies done in the past and address many of the limitations due to the scope of the studies and/or the scientific techniques available at that time. We have successfully developed an H1N1 model that had been used to address important questions regarding correlates of protection and is now being implemented to develop new drugs and vaccines. We hope to develop H3N2 models that can be just as useful.
The primary objective of this study is to determine the dose of influenza A H3N2 human challenge virus that will induce a mild to moderate uncomplicated influenza infection in healthy volunteers. This protocol will examine some of the basic questions that remain unanswered regarding the pathogenesis of H3N2 influenza in humans, namely, a detailed clinical and immunological characterization of uncomplicated influenza viral pathogenesis in healthy adult volunteers.
Secondary objectives will evaluate clinical disease, length of viral shedding, and pathogenesis in those with influenza infection including identification of clinical markers of the disease. Notably, the exploratory objectives will seek to discover viral factors necessary for human infection/adaptation and to evaluate host immune response, viral replication, viral fitness, and the intrahost evolution.
Collaboration between NIAID investigators and outside scientists will generate opportunities to further develop and expand areas of clinical influenza research based on the proposed H3N2 challenge model.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 49
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description 1 Live recombinantly derived A/Bethesda/MM1/H3N2 virus The human challenge virus will be administered intranasally to each participant using a nasal sprayer. A total volume of up to 2mL of virus will be administered.
- Primary Outcome Measures
Name Time Method Determine the minimally to moderately infective dose (MMID) of influenza A H3N2 human challenge virus, defined as the dose that induces uncomplicated mild to moderate influenza infection in at least 60% of healthy volunteers. 2 yr
- Secondary Outcome Measures
Name Time Method Evaluate clinical disease, identify clinical markers, and observe initiation of shedding, length of shedding, and pathogenesis in participants with influenza infection. 1yr
Trial Locations
- Locations (1)
National Institutes of Health Clinical Center, 9000 Rockville Pike
🇺🇸Bethesda, Maryland, United States