TINO: T Cells in the Nose of Older Adults

Aging Clinical Trial

— TINO  

Official title:

TINO: Identifying the Underlying Mechanisms and Consequences of the Loss of Nasal T Cells in Vital and Frail Older Individuals

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06039527
• Other study ID #: P21.066
• Secondary ID: NL77841.058.21
• Status: Recruiting
• Start date: January 24, 2021
• Est. completion date: May 2025

Study information

• Verified date: June 2024
• Source: Leiden University Medical Center
• Contact: Simon P Jochems, PhD
• Phone: +31715261328
• Email: s.p.jochems[@]lumc.nl
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Rationale: Individuals with advanced age are at a progressively increasing risk of acquiring lower respiratory tract infections. Besides calendar age, the degree of frailty also associates with increased susceptibility to pneumonia requiring hospitalization. How alterations in the mucosal immune system with advanced age predispose to infections remains unclear as access to relevant tissue samples is limited. With minimally-invasive nasal sampling methods, it was recently observed that in vital older adults, both CD4+ T cells and CD8+ T cells are selectively lost from the nasal mucosa. However, the exact phenotype, underlying mechanisms, key molecules and consequences of this have not yet been investigated.

Objective:

Elucidate the mechanisms underlying the loss of nasal T cells and characterize in depth the differences of T cells in young and older adults and associate this loss with susceptibility to infections.

Study design: Prospective cohort study

Study population: Participants will be recruited from 3 groups:

• healthy young adults (18-30 years, n=50)

• vital older adults (>65 years, n=60)

• frail elderly (>65 years, n=60). This group includes individuals without a history of recurrent respiratory infections or with >2 self-reported episodes of respiratory infection in the past year.

Main study parameters/endpoints: Frequency of nasal CD8+ T cells in young adults and frail older adults.

Secondary study parameters/endpoints:

• Phenotype (subsets, activation status), functionality, transcriptomic state, clonality and frequency of nasal and blood T cell populations

• Stability of T cells and other immune parameters, as described for main study parameter, during a second sample after 3 months.

• Analysis of other immune populations as for main study parameter

• Concentration of nasal and systemic factors (e.g. cytokines and metabolites) and their association with T cells and other immune populations

• Respiratory tract microbiota profiles and presence of asymptomatic viral infections and their association with T cells and other immune parameters

• Chronological and biological age, sex, and other immunologically relevant parameters with T cell populations and other immune parameters

• Alteration of T cell phenotype, during and following respiratory tract infections. Levels of antigen-specific T cells and other immune parameters in nose and blood post infection.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 170
• Est. completion date: May 2025
• Est. primary completion date: May 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

•Adults able and willing to provide informed consent.

Specific inclusion criteria per group:

• Young adults aged 18-30 years old

• Healthy elderly aged >65 years old

• Frail elderly >65 years old

• Clinical Frailty score healthy elderly 1-3

• Clinical Frailty score frail elderly >3

• Self-reported respiratory tract infection in previous year healthy elderly 0-1

• Self-reported respiratory tract infection in previous year frail elderly 0-1 or >1

Exclusion Criteria:

• Incompetence to provide informed consent prior or during study

• Current smoker or >40 pack year history

• History of severe nose bleedings

• Diagnosed with asthma, COPD or chronic rhinosinusitis

• Use of inhalation corticosteroids or antibiotics in the past 6 weeks

• Current use of anti-coagulants (to prevent nosebleeds). Platelet inhibitors like acetylsalicylzuur (Ascal) are allowed.

• Respiratory tract infection or common cold in the past 2 weeks

• Immunocompromised individuals (with primary immune deficiency or secondary immune deficiency)

• Life expectancy <28 days in the opinion of study physician

• Vaccination in the 2 months prior to study start. A potential subject that is only excluded from participation based on a recent vaccination will be asked to re-participate 2 months post vaccination.

Related Conditions & MeSH terms

• Aging
• Respiratory Tract Infections

Locations

Country	Name	City	State
Netherlands	Leiden University Medical Center	Leiden	Zuid Holland

Sponsors (1)

Lead Sponsor	Collaborator
Leiden University Medical Center

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Frequency of nasal CD8+ T cells in young adults and frail older adults.	CD8 T cells relative to nasal epithelial cells (ratio)	baseline sample or month 3 sample
Secondary	Phenotype of nasal and blood T cell populations in young adults, healthy older adults and frail older adults that suffer from recurrent respiratory tract infections or not.	percentage of T cells and T cell subsets	baseline sample or month 3 sample
Secondary	Functionality of nasal and blood T cell populations in young adults, healthy older adults and frail older adults that suffer from recurrent respiratory tract infections or not.	percentage of T cells responding to in vitro stimulations	baseline sample or month 3 sample
Secondary	Transcriptomic cluster composition of nasal and blood T cell populations in young adults, healthy older adults and frail older adults that suffer from recurrent respiratory tract infections or not, as frequency of T cell subsets.	T cell clusters based on gene expression patterns	baseline sample or month 3 sample
Secondary	Clonality of nasal and blood T cell populations in young adults, healthy older adults and frail older adults that suffer from recurrent respiratory tract infections or not.	Number and proportion of TCR clones	baseline sample or month 3 sample
Secondary	Stability of nasal T cells, as described for main study parameter, during a second sample after 3 months.	CD8 T cells relative to nasal epithelial cells (ratio)	baseline sample versus month 3 sample
Secondary	Stability of nasal immune populations, during a second sample after 3 months.	immune cell populations relative to nasal epithelial cells (ratio)	baseline sample versus month 3 sample
Secondary	Comparison of nasal immune cell populations between young adults, vital and frail elderly	ratio to epithelial cells	baseline sample or month 3 sample
Secondary	Comparison of peripheral immune cell populations between young adults, vital and frail elderly	percentage of total CD45+ cells	baseline sample or month 3 sample
Secondary	Concentration of nasal and systemic cytokines	concentrations	baseline sample or month 3 sample
Secondary	Concentration of nasal and systemic metabolitesother immune populations	concentrations	baseline sample or month 3 sample
Secondary	Respiratory tract microbiota profiles and their association with T cells and other immune parameters	microbiota abundance (total sum scaling)	baseline sample or month 3 sample
Secondary	Presence of asymptomatic viral infections and their association with T cells and other immune parameters	viral of loads (Ct)	baseline sample or month 3 sample
Secondary	Effect of sex on aging effects of nasal immune populations	ratio to nasal epithelial cells	baseline sample or month 3 sample
Secondary	Effect of sex on aging effects of blood immune populations	percentage of CD45+ cells	baseline sample or month 3 sample
Secondary	Frequencies of antigen-specific T cells in nose post infection.	antigen-specific T cells as percentage of T cells	symptom onset and 1, 3 and 5 months later
Secondary	Frequencies of antigen-specific T cells in blood post infection.	antigen-specific T cells as percentage of T cells	symptom onset and 1, 3 and 5 months later