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

RSV Infection Clinical Trial

— INFLAMMAGE  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03728413
• Other study ID #: 11/LO/1023_V3
• Status: Recruiting
• Phase: N/A
• Start date: March 5, 2019
• Est. completion date: September 28, 2024

Study information

• Verified date: August 2019
• Source: Imperial College London
• Contact: Christopher Chiu, MRCP FRCPath PhD
• Phone: +442083832301
• Email: c.chiu[@]imperial.ac.uk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 108
• Est. completion date: September 28, 2024
• Est. primary completion date: September 28, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Infection
• Respiratory Syncytial Virus Infections
• RSV Infection

Intervention

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.

Locations

Country	Name	City	State
United Kingdom	Imperial College London	London

Sponsors (1)

Lead Sponsor	Collaborator
Imperial College London

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Antibody responses to RSV infection	Frequency of RSV specific antibodies at 0,7,10,14 and 28 days post inoculation	Through study completion, up to 5 years
Other	T cell responses to RSV infection	Frequency of RSV specific T cells at 0,7,10,14 and 28 days post inoculation	Through study completion, up to 5 years
Primary	RSV challenge remains safe and tolerable in older adults.	Safety and tolerability of experimental challenge with RSV Memphis 37, assessed by the number of participants with study-related adverse events	Through pilot study completion, up to 1 year
Secondary	Symptom severity in RSV infection	Self-reported upper and lower respiratory and systemic symptoms by diary card	Through study completion, up to 5 years
Secondary	Viral load measurement in RSV infection	Change from baseline in viral load by qPCR of 7 days post inoculation.	Through study completion, up to 5 years