Back to resultsBiomarkers Predicting Infectivity in an Experimental Human Influenza Model (PRESAGE)
Primary Purpose
Influenza A
Status
Unknown status
Phase
Phase 1
Locations
United Kingdom
Study Type
Interventional
Intervention
Influenza A/California/04/09
Sponsored by
About this trial
This is an interventional basic science trial for Influenza A
Eligibility Criteria
Inclusion Criteria:
- Healthy persons aged 18 to 55 years, able to give informed consent
Exclusion Criteria:
- Chronic respiratory disease (asthma, chronic obstructive pulmonary disease, rhinitis, sinusitis) in adulthood
- Inhaled bronchodilator or steroid use within the last 12 months
- Use of any medication or other product (prescription or over-the-counter) for symptoms of rhinitis or nasal congestion within the last 6 months
- Acute upper respiratory infection or sinusitis in the past 6 weeks
- Smoking in the past 6 months OR >5 pack-year lifetime history
- Subjects with allergic symptoms present at baseline
- Clinically relevant abnormality on chest X-ray
- Those in close domestic contact (i.e. sharing a household with, caring for, or daily face to face contact) with children under 3 years, the elderly (>65 years), immunosuppressed persons, or those with chronic respiratory disease
- Subjects with known or suspected immune deficiency
- Receipt of systemic glucocorticoids (in a dose ≥ 5 mg prednisone daily or equivalent) within one month, or any other cytotoxic or immunosuppressive drug within 6 months prior to challenge
- Known immunoglobulin A deficiency, immotile cilia syndrome, or Kartagener's syndrome
- History of frequent nose bleeds
- Any significant medical condition or prescribed drug deemed by the study doctor to make the participant unsuitable for the study
- Pregnant or breastfeeding women
- Positive urine drug screen
- Detectable baseline haemagglutination inhibition titres against influenza challenge strains
- History of hypersensitivity to eggs, egg proteins, gentamicin, gelatin or arginine, or with life-threatening reactions to previous influenza vaccinations
All women of childbearing age will have a pregnancy test performed prior to virus inoculation to exclude pregnancy and be required to use contraception throughout the study.
Sites / Locations
- Imperial College London
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Influenza A/California/04/2009
Arm Description
Participants will be inoculated with Influenza A/California/04/09 3.5x10(4) tissue culture infective dose 50% (TCID50) in 1 mL in Dulbecco's phosphate buffered saline (DPBS) delivered by intranasal drops. They will then be monitored as in-patients for 10 days with daily clinical assessment and blood and respiratory tract sampling. Following discharge, they will be followed up for up to 6 months post-inoculation.
Outcomes
Primary Outcome Measures
Viral load
Nasal wash viral load by quantitative polymerase chain reaction (qPCR)
Secondary Outcome Measures
Symptoms
Self-reported upper and lower respiratory and systemic symptoms by diary card
Differentially expressed genes in blood
Differentially expressed genes analysed by RNA sequencing of whole blood
Differentially expressed genes in nasal curettage
Differentially expressed genes analysed by RNA sequencing of nasal curettage samples
Metabolomics in serum
Differentially expressed metabolites in serum by mass spectrometry
Full Information
NCT ID
NCT03207152
First Posted
June 30, 2017
Last Updated
July 3, 2018
Sponsor
Duke University
Collaborators
United States Department of Defense, Imperial College of London
1. Study Identification
Unique Protocol Identification Number
NCT03207152
Brief Title
Biomarkers Predicting Infectivity in an Experimental Human Influenza Model
Acronym
PRESAGE
Official Title
Biomarkers Predicting Infectivity in an Experimental Human Influenza Model
Study Type
Interventional
2. Study Status
Record Verification Date
July 2018
Overall Recruitment Status
Unknown status
Study Start Date
September 11, 2017 (Actual)
Primary Completion Date
May 8, 2018 (Actual)
Study Completion Date
February 28, 2019 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Duke University
Collaborators
United States Department of Defense, Imperial College of London
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No
5. Study Description
Brief Summary
This study aims to test the hypothesis that gene transcriptional changes occur within 24 hours of virus exposure in the blood and nasal mucosa, and to identify early biomarker signatures that are predictive of higher viral shedding at the peak of disease
Detailed Description
This study will systematically investigate the early pre-symptomatic period following exposure to influenza in humans. The data obtained will be essential for further understanding of the natural history of human antiviral responses, and will allow us to identify a panel of biomarkers that can predict which individuals will go on to more severe symptoms and higher viral shedding, so that treatments and other interventions can be made at an early stage.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Influenza A
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
50 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Influenza A/California/04/2009
Arm Type
Experimental
Arm Description
Participants will be inoculated with Influenza A/California/04/09 3.5x10(4) tissue culture infective dose 50% (TCID50) in 1 mL in Dulbecco's phosphate buffered saline (DPBS) delivered by intranasal drops. They will then be monitored as in-patients for 10 days with daily clinical assessment and blood and respiratory tract sampling. Following discharge, they will be followed up for up to 6 months post-inoculation.
Intervention Type
Biological
Intervention Name(s)
Influenza A/California/04/09
Intervention Description
Good Manufacturing Practices-certified Influenza A/California/04/09 3.5x10(4) TCID50 in 1 mL in DPBS delivered by intranasal drops
Primary Outcome Measure Information:
Title
Viral load
Description
Nasal wash viral load by quantitative polymerase chain reaction (qPCR)
Time Frame
28 days
Secondary Outcome Measure Information:
Title
Symptoms
Description
Self-reported upper and lower respiratory and systemic symptoms by diary card
Time Frame
28 days
Title
Differentially expressed genes in blood
Description
Differentially expressed genes analysed by RNA sequencing of whole blood
Time Frame
9 months
Title
Differentially expressed genes in nasal curettage
Description
Differentially expressed genes analysed by RNA sequencing of nasal curettage samples
Time Frame
9 months
Title
Metabolomics in serum
Description
Differentially expressed metabolites in serum by mass spectrometry
Time Frame
9 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Healthy persons aged 18 to 55 years, able to give informed consent
Exclusion Criteria:
Chronic respiratory disease (asthma, chronic obstructive pulmonary disease, rhinitis, sinusitis) in adulthood
Inhaled bronchodilator or steroid use within the last 12 months
Use of any medication or other product (prescription or over-the-counter) for symptoms of rhinitis or nasal congestion within the last 6 months
Acute upper respiratory infection or sinusitis in the past 6 weeks
Smoking in the past 6 months OR >5 pack-year lifetime history
Subjects with allergic symptoms present at baseline
Clinically relevant abnormality on chest X-ray
Those in close domestic contact (i.e. sharing a household with, caring for, or daily face to face contact) with children under 3 years, the elderly (>65 years), immunosuppressed persons, or those with chronic respiratory disease
Subjects with known or suspected immune deficiency
Receipt of systemic glucocorticoids (in a dose ≥ 5 mg prednisone daily or equivalent) within one month, or any other cytotoxic or immunosuppressive drug within 6 months prior to challenge
Known immunoglobulin A deficiency, immotile cilia syndrome, or Kartagener's syndrome
History of frequent nose bleeds
Any significant medical condition or prescribed drug deemed by the study doctor to make the participant unsuitable for the study
Pregnant or breastfeeding women
Positive urine drug screen
Detectable baseline haemagglutination inhibition titres against influenza challenge strains
History of hypersensitivity to eggs, egg proteins, gentamicin, gelatin or arginine, or with life-threatening reactions to previous influenza vaccinations
All women of childbearing age will have a pregnancy test performed prior to virus inoculation to exclude pregnancy and be required to use contraception throughout the study.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Christopher Chiu, BMBCh PhD
Organizational Affiliation
Imperial College London
Official's Role
Principal Investigator
Facility Information:
Facility Name
Imperial College London
City
London
ZIP/Postal Code
W12 0NN
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Data will be shared with Duke university, such as ethnicity and age. It will be identifiable only by their unique study code, with no personal details.
Learn more about this trial
Biomarkers Predicting Infectivity in an Experimental Human Influenza Model
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