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The Impact of Age on Adaptive Immunity in Adults Infected With Respiratory Syncytial Virus (INFLAMMAGE)

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ClinicalTrials.gov Identifier: NCT03728413
Recruitment Status : Recruiting
First Posted : November 2, 2018
Last Update Posted : August 14, 2019
Sponsor:
Information provided by (Responsible Party):
Imperial College London

Tracking Information
First Submitted Date  ICMJE October 16, 2018
First Posted Date  ICMJE November 2, 2018
Last Update Posted Date August 14, 2019
Actual Study Start Date  ICMJE March 5, 2019
Estimated Primary Completion Date September 28, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 31, 2018)
RSV challenge remains safe and tolerable in older adults. [ Time Frame: Through pilot study completion, up to 1 year ]
Safety and tolerability of experimental challenge with RSV Memphis 37, assessed by the number of participants with study-related adverse events
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 31, 2018)
  • Symptom severity in RSV infection [ Time Frame: Through study completion, up to 5 years ]
    Self-reported upper and lower respiratory and systemic symptoms by diary card
  • Viral load measurement in RSV infection [ Time Frame: Through study completion, up to 5 years ]
    Change from baseline in viral load by qPCR of 7 days post inoculation.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: October 31, 2018)
  • Antibody responses to RSV infection [ Time Frame: Through study completion, up to 5 years ]
    Frequency of RSV specific antibodies at 0,7,10,14 and 28 days post inoculation
  • T cell responses to RSV infection [ Time Frame: Through study completion, up to 5 years ]
    Frequency of RSV specific T cells at 0,7,10,14 and 28 days post inoculation
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE The Impact of Age on Adaptive Immunity in Adults Infected With Respiratory Syncytial Virus
Official Title  ICMJE The Impact of Age on Adaptive Immunity in Adults Infected With Respiratory Syncytial Virus
Brief Summary This study will for the first time systematically investigate the immune responses in an elderly cohort challenged with a well-defined RSV inoculum. With a global aging population and continuing difficulties in generating vaccines that can reliably induce protective immunity in the elderly, these data will indicate the targets at which development of vaccines against RSV and other infections should be directed.
Detailed Description Respiratory syncytial virus (RSV) is one of the most common causes of chest infection worldwide, with 64 million episodes and 160,000 deaths each year. Despite this, it remains an underappreciated health problem and there are currently no specific treatments or vaccines against it. Although RSV infection is most frequent in young children, the majority of deaths occur in older adults, particularly in those with underlying heart and lung disease. This is believed to be due in part to the ageing immune system's reduced ability to protect against infection and symptomatic disease. However, little is known about the way human immune responses to RSV infection in older individuals differ from those of younger people. Further understanding of the mechanisms underlying immunity and potential impairments in these higher-risk people are therefore necessary. This project aims to study the role of T cells (which destroy virus-infected cells and are likely to be essential for recovery from infection) in healthy older volunteers after they have been given an RSV-induced common cold. Samples will be taken from the blood and respiratory tract in order to identify the differences in T cell responses that occur in older adults compared with their younger counterparts. Participants will be carefully screened to ensure they do not have any underlying health problems that might make them more at risk of severe disease and will be monitored closely throughout the course of infection. The investigators anticipate that T cell function even in healthy older individuals will be impaired compared to young adults, thus contributing in those with additional health problems to more severe disease. By analysing the networks of genes that are switched on and off, the investigators aim to identify the particular defects underlying these functional defects in order to ultimately define targets for novel treatments and T cell-stimulating vaccines.
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Condition  ICMJE RSV Infection
Intervention  ICMJE Biological: RSV A Memphis 37

Subjects will be inoculated using intra-nasal drops with diluted inoculum at a given dose divided equally between the two nostrils. Dose: Good Manufacturing Practices-certified RSV Memphis 37 10(4) PFU in 1ml, 25% sucrose/Dulbecco's Modification of Eagle's Medium. Inoculations using intranasal drops will be done using a 1mL pipette with subjects supine. This will be done slowly with sufficient interval between each inoculation (2-3 minutes) to ensure maximum contact time between with the nasal and pharyngeal mucosa. Subjects will be asked not to swallow during the procedure to ensure maximal pharyngeal contact.

Following inoculation, advice regarding hand hygiene will be given, subjects will be provided with alcohol hand gel and facemasks to reduce spread of virus in the environment.

Study Arms  ICMJE
  • Elderly Non-smoking
    RSV A Memphis 37 will be given as intra-nasal drops.
    Intervention: Biological: RSV A Memphis 37
  • Elderly ex and current smokers
    RSV A Memphis 37 will be given as intra-nasal drops.
    Intervention: Biological: RSV A Memphis 37
  • Young non-smokers
    RSV A Memphis 37 will be given as intra-nasal drops.
    Intervention: Biological: RSV A Memphis 37
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 31, 2018)
108
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE September 28, 2024
Estimated Primary Completion Date September 28, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Healthy persons aged 18 to 40 years or 60 to 75 years, able to give informed consent
  • Current smoker/ex-smoker of at least 20 pack years or non-smoker
  • Spirometry within the normal range for age and height (+/- 15%)
  • FEV1/FVC >70% pre-bronchodilator

Exclusion Criteria:

  • Chronic respiratory disease (asthma, COPD, rhinitis, sinusitis) in adulthood
  • Inhaled bronchodilator or steroid use within the last 12 months
  • Habitual 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
  • 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, other elderly adults (>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 IgA 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
  • Women of childbearing potential must have a negative hCG urine pregnancy test *
  • Positive urine drug screen
  • Women of childbearing potential will have a pregnancy test performed prior to virus inoculation to exclude pregnancy and be required to use contraception throughout the study.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Contact: Christopher Chiu, MRCP FRCPath PhD +442083832301 c.chiu@imperial.ac.uk
Contact: Zoe Gardener, BSc +442083832301 z.gardener@imperial.ac.uk
Listed Location Countries  ICMJE United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03728413
Other Study ID Numbers  ICMJE 11/LO/1023_V3
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Plan Description: Data may be shared, all data will be anonymised.
Responsible Party Imperial College London
Study Sponsor  ICMJE Imperial College London
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Christopher Chiu Imperial College London
PRS Account Imperial College London
Verification Date August 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP