Biomarkers Predicting Infectivity in an Experimental Human Influenza Model

Phase 1

• Conditions: Influenza A
• Interventions: Biological: Influenza A/California/04/09

• Registration Number: NCT03207152
• Lead Sponsor: Duke University

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.

Study Timeline

• Study First Submitted: 2017-06-30
• Study First Submitted QC: 2017-06-30
• Study First Posted: 2017-07-02
• Study Start: 2017-09-11
• Primary Completion: 2018-05-08
• Status Verified: 2018-07
• Last Update Submitted: 2018-07-03
• Last Update Posted: 2018-07-06
• Study Completion: 2019-02-28

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

• Healthy persons aged 18 to 55 years, able to give informed consent

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Influenza A/California/04/2009	Influenza A/California/04/09	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.

Primary Outcome Measures

Name	Time	Method
Viral load	28 days	Nasal wash viral load by quantitative polymerase chain reaction (qPCR)

Secondary Outcome Measures

Name	Time	Method
Symptoms	28 days	Self-reported upper and lower respiratory and systemic symptoms by diary card
Metabolomics in serum	9 months	Differentially expressed metabolites in serum by mass spectrometry
Differentially expressed genes in blood	9 months	Differentially expressed genes analysed by RNA sequencing of whole blood
Differentially expressed genes in nasal curettage	9 months	Differentially expressed genes analysed by RNA sequencing of nasal curettage samples

Trial Locations

Locations (1)

Imperial College London; 🇬🇧 London, United Kingdom