Biomarkers Predicting Infectivity in an Experimental Human Influenza Model

Influenza A Clinical Trial

— PRESAGE  

Official title:

Biomarkers Predicting Infectivity in an Experimental Human Influenza Model

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT03207152
• Other study ID #: Pro00082500
• Status: Enrolling by invitation
• Phase: Phase 1
• Start date: September 11, 2017
• Est. completion date: February 28, 2019

Study information

• Verified date: July 2018
• Source: Duke University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 50
• Est. completion date: February 28, 2019
• Est. primary completion date: May 8, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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.

Related Conditions & MeSH terms

• Influenza A
• Influenza, Human

Intervention

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

Locations

Country	Name	City	State
United Kingdom	Imperial College London	London

Sponsors (3)

Lead Sponsor	Collaborator
Duke University	Imperial College of London, United States Department of Defense

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Viral load	Nasal wash viral load by quantitative polymerase chain reaction (qPCR)	28 days
Secondary	Symptoms	Self-reported upper and lower respiratory and systemic symptoms by diary card	28 days
Secondary	Differentially expressed genes in blood	Differentially expressed genes analysed by RNA sequencing of whole blood	9 months
Secondary	Differentially expressed genes in nasal curettage	Differentially expressed genes analysed by RNA sequencing of nasal curettage samples	9 months
Secondary	Metabolomics in serum	Differentially expressed metabolites in serum by mass spectrometry	9 months