Evaluating Modes of Influenza Transmission

NCT01710111 | Completed DMC

• 1 other identifier: 12074
• Study Type: interventional
• Target: 127
• Locations: 1 country
• Sites: 1

Brief Summary

The ways in which influenza is transmitted between people are uncertain; for example, we do not know if large droplets or fine particles (aerosols) matter most; both are produced by coughing and sneezing. This means we cannot say what precautions work best in real life. Improving our understanding is vital to allow the development of guidelines and policies to help reduce the transmission of both pandemic and seasonal flu. The aim of this study is to explore how influenza is spread, specifically by looking at the importance of spread via small particles (aerosols/droplet nuclei) that are carried in respiratory sprays e.g. produced by coughing and sneezing. The primary objective of this study is: To estimate the contribution of aerosols/droplet nuclei to influenza transmission by determining the secondary attack rate (SAR) of influenza in Recipients randomised to a control arm (no intervention - allowing all modes of transmission) compared to Recipients randomised to an intervention arm (face shield and hand hygiene - allowing only transmission by aerosols/droplet nuclei) when both groups of Recipients are exposed to Donor volunteers infected with influenza via intranasal drops. The hypothesis is that: The SAR will be lower in Recipients exposed only to aerosols/droplet nuclei (intervention arm) compared to those exposed to all modes of transmission (the control arm): aerosols/droplet nuclei, droplet spray (larger respiratory droplets) and transmission through contact.

Conditions

Influenza, Human

Keywords

Human challenge model; Quarantine study; Influenza virus; Modes of transmission; Droplet spray; Droplet nuclei; Secondary attack rate; Face shield; Hand hygiene; Fomites; Environmental deposition; Environmental dispersion

Outcome Measures

Primary Outcomes (1)

• Difference in Secondary Attack Rate (SAR)

  The primary endpoint is the difference in SAR of influenza in Recipients randomised to an intervention arm (face shield and hand hygiene -droplet nuclei transmission only) compared to Recipients randomised to a control arm (no intervention - all modes of transmission).

  Day -2 to day 28(±3)

Secondary Outcomes (4)

• Viral parameters of infection and association with infection transmission.

  Day 1 to day 10

• Clinical parameters of infection and association with infection transmission.

  Day 1 to day 10

• Environmental disposition of virus during infection.

  Day 1 to day 10

• Safety of experimental infection in both challenged and exposed volunteers.

  Day 1 to day 28(±3)

Study Arms (2)

Intervention Recipients Face Shield

EXPERIMENTAL

Face shield and repeat hand hygiene measures

Device: Intervention Recipients Face Shield

Control Recipients

NO INTERVENTION

No face shield and no repeat hand hygiene measures

Interventions

Intervention Recipients Face Shield DEVICE

Face shield and repeat hand hygiene measures

Intervention Recipients Face Shield

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Body Weight: A total body weight ≥50 kg and a Body mass index (BMI) \>18 (if BMI is \>32, a body fat percentage within WHO and NIH range for gender and age. BMI \[kg/m2\] = Body weight \[kg\] ÷ Height2 \[m2\]
• Contraception: Nonsterilised males must agree to refrain from fathering a child from the point of entering quarantine until the Day 28 follow up visit. Use of one effective form of contraception is acceptable. Sexually active females of childbearing potential must agree to use 2 effective methods of avoiding pregnancy that are deemed to be effective from the point of entry into the quarantine unit until the Day 28 follow up visit. Acceptable forms of effective contraception include:
• Established use of oral, injected or implanted hormonal methods of contraception.
• Placement of an intrauterine device (IUD) or intrauterine system (IUS).
• Barrier methods of contraception: Condom or Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository.
• Male sterilisation (with the appropriate postvasectomy documentation of the absence of sperm in the ejaculate). \[For female subjects on the study, the vasectomised male partner should be the sole partner for that subject\].
• True abstinence: When this is in line with the preferred and usual lifestyle of the subject. \[Periodic abstinence (e.g., calendar, ovulation, symptothermal, postovulation methods) and withdrawal are not acceptable methods of contraception\].
• Informed Consent: An informed consent document signed and dated by the subject and investigator
• Serosuitability: Serosuitable for challenge virus

You may not qualify if:

• Smoking: Significant history of any tobacco use at any time (≥ total 10 pack year history, eg. one pack a day for 10 yrs)
• Pregnancy/Lactation: Subjects who are pregnant or nursing, or who have a positive pregnancy test at any point in study
• Previous Medical History: Presence of significant acute or chronic, uncontrolled medical illness, that in the view of Investigator(s)is associated with increased risk of complications of respiratory viral illness
• Pulmonary Function: Abnormal pulmonary function in the opinion of the investigator evidenced by clinically significant abnormalities in spirometry
• Immune: History or evidence of autoimmune disease or known impaired immune responsiveness (of any cause)
• Asthma: History of asthma, COPD, pulmonary hypertension, reactive airway disease, or any chronic lung condition of any aetiology.History of childhood asthma until and including the age of 12 is acceptable.
• HIV \& Hepatitis: Positive HIV, hepatitis B (HBV), or hepatitis C (HCV) antibody screen.
• Anatomic abnormalites of nasopharynx:Significant abnormality altering anatomy of nose or nasopharynx
• Epistaxis: Clinically significant history of epistaxis
• Nasal Surgery: Any nasal or sinus surgery within 6 months of inoculation
• Fainting: Recent (within the last 3 years of the screening visit) and/or recurrent history of clinically significant autonomic dysfunction (e.g. recurrent episodes of fainting, palpitations, etc)
• Lab Test/ECG: Laboratory test or ECG which is abnormal and deemed by investigator(s) to be clinically significant.
• Drugs of abuse etc: Confirmed Positive test for class A drugs or alcohol that cannot be satisfactorily explained
• Venous Access: Venous access deemed inadequate for phlebotomy (and IV infusion) demands of study
• Hayfever: Subjects symptomatic with hayfever on admission or prior to inoculation.

Sponsors & Collaborators

• University of Nottingham: lead
• Retroscreen Virology Ltd.: collaborator
• Wake Forest University Health Sciences: collaborator
• University of Maryland: collaborator
• University of Leeds: collaborator
• Building Services Research and Information Association (BSRIA): collaborator
• University College, London: collaborator
• Mount Sinai Hospital, New York: collaborator
• Imperial College London: collaborator
• University of Glasgow: collaborator
• Sydney Children's Hospitals Network: collaborator

Study Sites (1)

Retroscreen Virology Ltd

London, E1 2AX, United Kingdom

Location

Related Publications (1)

• Bueno de Mesquita PJ, Noakes CJ, Milton DK. Quantitative aerobiologic analysis of an influenza human challenge-transmission trial. Indoor Air. 2020 Nov;30(6):1189-1198. doi: 10.1111/ina.12701. Epub 2020 Jun 15.

  PMID: 32542890 DERIVED

MeSH Terms

Conditions

Influenza, Human

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases

Study Officials

• Jonathan S Nguyen-Van-Tam, BM, BS, DM

  University of Nottingham

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 9, 2012
• First Posted: October 18, 2012
• Study Start: January 1, 2013
• Primary Completion: July 1, 2013
• Study Completion: July 1, 2013
• Last Updated: January 15, 2014

Record last verified: 2014-01

Locations

GB (1)