- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01646138
Influenza A 2009 H1N1 Challenge Study in Healthy Adults
Influenza A 2009 H1N1 Human Challenge Study in Healthy Adult Volunteers
Background:
- A challenge study exposes a person to a disease and allows researchers to study the disease through the body's healing process. An influenza challenge study that looks at different amounts of the flu virus can provide more information on the smallest amount needed to cause an infection. Researchers want to give one dose of the Influenza A H1N1 virus to healthy volunteers to see how the body responds to the virus.
Objectives:
- To find the smallest dose of Influenza A H1N1 virus that may cause a mild to moderate flu infection in a healthy adult.
- To study how the body s immune system responds to the virus.
Eligibility:
- Healthy volunteers at least 18 years of age.
- Participants must be willing to remain in isolation for a minimum of 9 days.
Design:
- Participants will be admitted to a hospital inpatient isolation unit. They will be screened with a physical exam and medical history. They will also have heart and lung function tests. Blood, urine, and nasal swab/wash samples will be collected.
- Participants will receive a single nasal spray of the flu virus. They will stay on the inpatient unit for at least 9 days.
- Participants will be monitored for the length of their stay. They will have frequent blood tests and other procedures as needed.
- Participants will be allowed to go home once they have had two negative tests for the virus. The tests will be given on two consecutive days....
Study Overview
Status
Conditions
Intervention / Treatment
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.
Previous human challenge studies have addressed some aspects of the natural history of influenza by evaluating the timing of viral replication, shedding, clinical symptoms, and innate and adaptive immune responses. Although these studies have provided important information, in the United States, all but 1 were performed prior to 1990. Without exception, these studies had limitations due to the scope of the study and/or the scientific techniques available at that time.
The primary objective of this study is to determine the dose of influenza A 2009 H1N1 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 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 National Institute of Allergy and Infectious Diseases (NIAID) investigators and outside scientists will generate opportunities to further develop and expand areas of clinical influenza research based on the proposed challenge model.
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
-
-
Maryland
-
Bethesda, Maryland, United States, 20892
- National Institutes of Health Clinical Center, 9000 Rockville Pike
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
-INCLUSION CRITERIA:
- Greater than or equal to 18 and less than or equal to 50 years of age.
- Agrees to not use tobacco products during participation in this study.
- Willingness to remain in isolation for the duration of viral shedding (at a minimum 9 days) and to comply with all study requirements.
A female participant is eligible for this study if she is not pregnant or breast feeding and 1 of the following:
- Of non-childbearing potential (i.e., women who have had a hysterectomy or tubal ligation or are postmenopausal, as defined by no menses in greater than or equal to 1 year).
- Of childbearing potential but agrees to practice effective contraception or abstinence for 4 weeks prior to and 8 weeks after administration of the influenza challenge virus. Acceptable methods of contraception include 1 or more of the following: 1) male partner who is sterile prior to the female participant s entry into the study and is the sole sexual partner for the female participant; 2) implants of levonorgestrel; 3) injectable progestogen; 4) an intrauterine device with a documented failure rate of < 1%; 5) oral contraceptives; and 6) double barrier methods including diaphragm or condom with a spermicide.
- Willing to have samples stored for future research.
- Prechallenge serum hemagglutination-inhibition titer against the challenge strain of 1:16 or less.
- HIV uninfected.
EXCLUSION CRITERIA:
Presence of self-reported or medically documented significant medical condition including but not limited to:
- Chronic pulmonary disease (e.g., asthma, emphysema).
- Chronic cardiovascular disease (e.g., cardiomyopathy, congestive heart failure, cardiac surgery, ischemic heart disease, known anatomic defects).
- Chronic medical conditions requiring close medical follow-up or hospitalization during the past 5 years (e.g., diabetes mellitus, renal dysfunction, hemoglobinopathies).
- Immunosuppression or ongoing malignancy.
- Neurological and neurodevelopmental conditions (e.g., cerebral palsy, epilepsy, stroke, seizures).
- Postinfectious or postvaccine neurological sequelae.
Have close or household (i.e., share the same apartment or house) high-risk contacts including but not limited to:
- Persons greater than or equal to 65 years of age.
- Children < 5 years of age.
- Residents of nursing homes.
Persons of any age with significant chronic medical conditions such as:
- Chronic pulmonary disease (e.g., asthma).
- Chronic cardiovascular disease (e.g., cardiomyopathy, congestive heart failure, cardiac surgery, ischemic heart disease, known anatomic defects).
- Contacts who required medical follow-up or hospitalization during the past 5 years because of chronic metabolic disease (e.g., diabetes mellitus, renal dysfunction, hemoglobinopathies).
- Immunosuppression or cancer.
- Neurological and neurodevelopmental conditions (e.g., cerebral palsy, epilepsy, stroke, seizures).
- Children and teenagers who are receiving long-term aspirin therapy.
- Women who are pregnant or who are trying to become pregnant.
- Individual with body mass index (BMI) less than or equal to 18.5 and greater than or equal to 40.
- Smokes more than 4 cigarettes or other tobacco products on weekly basis.
- Complete blood count (CBC) with differential outside of the NIH Department of Laboratory Medicine (DLM) normal reference range and deemed clinically significant by the PI.
- Chemistries in the acute care, mineral, and/or hepatic panels, and/or any of the following: lactate dehydrogenase, uric acid, creatine kinase, and total protein outside of the NIH DLM normal reference range and deemed clinically significant by the PI.
- Urinalysis outside of the NIH DLM normal reference range and deemed clinically significant by the PI.
- Clinically significant abnormality on electrocardiogram .
- Clinically significant abnormality as deemed by the PI on echocardiographic testing.
- Recent acute illness within 1 week of admission to the isolation facility.
- Known allergy to treatments for influenza (including but not limited to oseltamivir, nonsteroidals).
- Known allergy to 2 or more classes of antibiotics (e.g., penicillins, cephalosporins, fluoroquinolones, or glycopeptides).
- Receipt of blood or blood products (including immunoglobulins) within 3 months prior to enrollment.
- Receipt of any unlicensed drug within 3 months or 5.5 half lives (whichever is greater) prior to enrollment.
- Receipt of any unlicensed vaccine within 6 months prior to enrollment.
- Self-reported or known history of current alcoholism or drug abuse, or positive urine/serum test for drugs of abuse (i.e., amphetamines, cocaine, benzodiazepines, opiates, or metabolites, but not tetrahydrocannabinol(THC) or metabolites).
- Self-reported or known history of psychiatric or psychological issues deemed by the PI to be a contraindication to protocol participation
- Known close contact with anyone known to have influenza in the past 7 days.
- Any condition that, in the judgment of the Principal Investigator, is a contraindication to protocol participation or impairs the volunteer s ability to give informed consent.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: BASIC_SCIENCE
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Challenge Virus
The Ca/04/2009/H1N1 Vero Grown Challenge Virus was administered intranasally to each participant using a nasal sprayer.
A total volume of up to 1 mL of virus will be administered.
|
The human challenge virus will be administered intranasally to each participant using a nasal sprayer.
A total volume of up to 1 mL of virus will be administered.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percent MMID
Time Frame: 67 days after influenza inoculation
|
Percent of individuals experiencing mild to moderate influenza infection (MMID, defined as active shedding and symptoms of influenza A) in each dosing group.
|
67 days after influenza inoculation
|
Collaborators and Investigators
Publications and helpful links
General Publications
- Hayden FG, Fritz R, Lobo MC, Alvord W, Strober W, Straus SE. Local and systemic cytokine responses during experimental human influenza A virus infection. Relation to symptom formation and host defense. J Clin Invest. 1998 Feb 1;101(3):643-9. doi: 10.1172/JCI1355.
- Jameson J, Cruz J, Ennis FA. Human cytotoxic T-lymphocyte repertoire to influenza A viruses. J Virol. 1998 Nov;72(11):8682-9. doi: 10.1128/JVI.72.11.8682-8689.1998.
- McAuley JL, Hornung F, Boyd KL, Smith AM, McKeon R, Bennink J, Yewdell JW, McCullers JA. Expression of the 1918 influenza A virus PB1-F2 enhances the pathogenesis of viral and secondary bacterial pneumonia. Cell Host Microbe. 2007 Oct 11;2(4):240-9. doi: 10.1016/j.chom.2007.09.001.
- Memoli MJ, Han A, Walters KA, Czajkowski L, Reed S, Athota R, Angela Rosas L, Cervantes-Medina A, Park JK, Morens DM, Kash JC, Taubenberger JK. Influenza A Reinfection in Sequential Human Challenge: Implications for Protective Immunity and "Universal" Vaccine Development. Clin Infect Dis. 2020 Feb 14;70(5):748-753. doi: 10.1093/cid/ciz281.
- Memoli MJ, Czajkowski L, Reed S, Athota R, Bristol T, Proudfoot K, Fargis S, Stein M, Dunfee RL, Shaw PA, Davey RT, Taubenberger JK. Validation of the wild-type influenza A human challenge model H1N1pdMIST: an A(H1N1)pdm09 dose-finding investigational new drug study. Clin Infect Dis. 2015 Mar 1;60(5):693-702. doi: 10.1093/cid/ciu924. Epub 2014 Nov 20.
Helpful Links
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ESTIMATE)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 120077
- 12-I-0077 (OTHER: NIH - National Institute of Allergy and Infectious Diseases)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Influenza
-
Novartis VaccinesCompletedInfluenza | Seasonal Influenza | Human Influenza | Influenza Due to Unspecified Influenza VirusBelgium
-
Gamaleya Research Institute of Epidemiology and...CompletedInfluenza A | Influenza A Virus Infection | Influenza Epidemic | Influenza H5N1Russian Federation
-
Vanderbilt University Medical CenterHuman Vaccines ProjectCompletedVaccine Reaction | Influenza | Influenza, Human | Influenza A | Influenza Type B | Influenza A H3N2 | Influenza A H1N1United States
-
NPO PetrovaxCompletedVaccine Reaction | Influenza | Influenza, Human | Influenza A | Acute Respiratory Infection | Influenza Type B | Flu | Influenza A H3N2 | Influenza A H1N1 | Flu, Human | Influenza EpidemicRussian Federation
-
National Institute of Allergy and Infectious Diseases...Completed
-
National Institute of Allergy and Infectious Diseases...Completed
-
National Institute of Allergy and Infectious Diseases...CompletedInfluenza Immunisation | Avian InfluenzaUnited States
-
National Institute of Allergy and Infectious Diseases...CompletedInfluenza | Influenza Immunisation | Avian InfluenzaUnited States
-
National Institute of Allergy and Infectious Diseases...CompletedInfluenza Immunisation | Avian InfluenzaUnited States
-
National Institute of Allergy and Infectious Diseases...National Institutes of Health (NIH)CompletedInfluenza AUnited States
Clinical Trials on Ca/04/2009/H1N1 Vero Grown Challenge Virus
-
National Institute of Allergy and Infectious Diseases...Completed
-
Immune Targeting Systems LtdCompleted