Assessment of Wearable Sensors During Experimental Human Influenza Infection (Sigma Plus)

The aim of the study is to investigate disease in volunteers deliberately infected with influenza A(H3N2), including biological markers of inflammation and immune response, and changes in physiological parameters including heart rate, respiratory rate, physical activity, oxygen saturation and electrocardiographic data during the onset of influenza infection. Ultimately, this may lead to prediction of symptomatic disease at an earlier stage to allow more effective interventions. The experimental medicine study design will involve human influenza infection challenge, whereby volunteers will be inoculated with influenza virus and monitored in hospital for 10 days as they develop and get better from flu. Continuously-monitoring wearable physiological sensors will be given to the participants 7 days before this and worn continuously until the end of the flu infection.

Study Overview

• Status: Completed
• Conditions: Influenza A H3N2
• Intervention / Treatment: Device: Lumee Oxygen Platform

Detailed Description

Influenza ('flu') is one of the most common causes of severe lung infection. Seasonal flu affects between 10 and 46% of the population each year and causes around 12 deaths in every 100,000 people infected. Furthermore, new strains of flu viruses emerge unpredictably every few years, causing pandemics that spread rapidly across the world. Since currently available antiviral drugs and vaccines cannot prevent these outbreaks, it is essential to be able to identify flu infections at an early stage to enable rapid treatment of individuals and implementation of public health measures.

The aim of the study is to investigate disease in volunteers deliberately infected with influenza A(H3N2), including biological markers of inflammation and immune response, and changes in physiological parameters including heart rate, respiratory rate, physical activity, oxygen saturation and electrocardiographic data during the onset of influenza infection. To achieve this, the investigators will recruit healthy volunteers and inoculate them with a flu virus, after which they will be observed in hospital while they develop a cold. Each volunteer will be given a number of devices that they will wear before and during infection. In addition, they will have blood and nasal samples taken to examine the way their immune system responds to infection. The resulting data will be analysed to see if the sensors data correlate with the onset of infection and these will be compared with measures of the immune response. Ultimately, the investigators anticipate that optimised sensor data from devices to be developed may be useful in rapidly detecting when someone is about to develop flu infection, so that they can quickly be treated and outbreaks may be identified at an early stage.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, W2 1PG
    • Imperial Clinical Research Facility, Imperial College London

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes

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 3 months
• Acute upper respiratory infection (URI 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
• Any ECG abnormality deemed clinically significant.
• 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 antibody 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.
• Participants may only recruited if they have previously been involved in research if they have completed the earlier study and are beyond the washout period of any administered drugs or period of effect of any intervention that would cause interference for either 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: Experimental: Influenza A; Participants will be inoculated with Influenza A/Belgium/4217/2015 at a dose of 5x105 TCID50 in a volume of 0,5mL via intranasal drops or spray. They will then be monitored as in-patients for 10 days with daily clinical assessment and blood, respiratory tract sampling, and sensor monitoring. Following discharge, they will be followed up for up to 6 months post-inoculation.

Device: Lumee Oxygen Platform; Two sensors will be inserted (one in the skin fo the upper arm and one on the side of the chest). A wireless patch reader is placed on top of the skin over the area where the sensor has been placed to measure local oxygen content.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of PCR-confirmed Influenza Infections	Nasal wash viral load by quantitative polymerase chain reaction (qPCR)	Baseline to day 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Algorithmic Detection of Heart Rate Abnormalities	Sensor data read-outs	Baseline to day 10
Tissue Oxygen Levels	Sensor data read-outs	Baseline to day 10
Participant-reported Total Symptom Score	Cumulative daily symptom score derived from self-reported upper and lower respiratory and systemic symptoms by diary card using the modified Jackson's symptom scoring system. Eight symptoms were scored: nasal obstruction, nasal discharge, sore throat, sneezing, cough, malaise, headache, and chills. Each symptom was scored 0-3, where 0=absent, 1=mild, 2=moderate and 3=severe. The maximum daily score is 24 and minimum daily score is 0.	Day 1, Day 3 and Day 10

Collaborators and Investigators

• Sponsor: Imperial College London
• Collaborators: Duke University; RTI International; Defense Advanced Research Projects Agency
• Investigators: Principal Investigator: Christopher Chiu, Imperial College London

Publications and helpful links

General Publications

• Temple DS, Hegarty-Craver M, Furberg RD, Preble EA, Bergstrom E, Gardener Z, Dayananda P, Taylor L, Lemm NM, Papargyris L, McClain MT, Nicholson BP, Bowie A, Miggs M, Petzold E, Woods CW, Chiu C, Gilchrist KH. Wearable Sensor-Based Detection of Influenza in Presymptomatic and Asymptomatic Individuals. J Infect Dis. 2023 Apr 12;227(7):864-872. doi: 10.1093/infdis/jiac262.

Study record dates

Study Major Dates

• Study Start (Actual): February 11, 2020
• Primary Completion (Actual): December 31, 2020
• Study Completion (Actual): May 17, 2021

Study Registration Dates

• First Submitted: November 12, 2019
• First Submitted That Met QC Criteria: December 18, 2019
• First Posted (Actual): December 19, 2019

Study Record Updates

• Last Update Posted (Actual): August 21, 2023
• Last Update Submitted That Met QC Criteria: August 17, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Influenza A H3N2
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Influenza, Human
• Other Study ID Numbers: 19HH5451

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data will be shared with Duke university, and RTI International, such as ethnicity and age. It will be identifiable only by their unique study code, with no personal details.
• IPD Sharing Access Criteria: According to study protocol
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes