Biomarkers Predicting Infectivity in an Experimental Human Influenza Model (PRESAGE)

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

Study Overview

• Status: Unknown
• Conditions: Influenza A
• Intervention / Treatment: Biological: Influenza A/California/04/09

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 Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, W12 0NN
    • Imperial College London

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Influenza A/California/04/2009; 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.

Biological: Influenza A/California/04/09; Good Manufacturing Practices-certified Influenza A/California/04/09 3.5x10(4) TCID50 in 1 mL in DPBS delivered by intranasal drops

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Viral load	Nasal wash viral load by quantitative polymerase chain reaction (qPCR)	28 days

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Duke University
• Collaborators: United States Department of Defense; Imperial College of London
• Investigators: Principal Investigator: Christopher Chiu, BMBCh PhD, Imperial College London

Study record dates

Study Major Dates

• Study Start (Actual): September 11, 2017
• Primary Completion (Actual): May 8, 2018
• Study Completion (Anticipated): February 28, 2019

Study Registration Dates

• First Submitted: June 30, 2017
• First Submitted That Met QC Criteria: June 30, 2017
• First Posted (Actual): July 2, 2017

Study Record Updates

• Last Update Posted (Actual): July 6, 2018
• Last Update Submitted That Met QC Criteria: July 3, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Influenza, Human
• Other Study ID Numbers: Pro00082500

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD 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.

Drug and device information, study documents

• 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