TINO: T Cells in the Nose of Older Adults (TINO)

• ClinicalTrials.gov Identifier: NCT06039527
• Recruitment Status: Recruiting
• First Posted: September 15, 2023
• Last Update Posted: December 15, 2023
• Sponsor: Leiden University Medical Center
• Information provided by (Responsible Party): Simon P Jochems, PhD, Leiden University Medical Center

Study Description

Brief 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.

Condition or disease
Respiratory Tract Infections; Aging

Study Design

• Study Type: Observational
• Estimated Enrollment: 170 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: TINO: Identifying the Underlying Mechanisms and Consequences of the Loss of Nasal T Cells in Vital and Frail Older Individuals
• Actual Study Start Date: January 24, 2021
• Estimated Primary Completion Date: May 2024
• Estimated Study Completion Date: July 2024

Groups and Cohorts

Group/Cohort
Young adults; N=50 of this group No intervention. Sampling at timepoint 0 and for 50% of the group another sample at 3 months If respiratory symptoms develop in the 3 months after timepoint 0, participants are invited to provide a NPS/OPS to identify causative agent, and if one is established, individuals are sampled 3 more times at months 1, 3 and 5 post symptom onset
Vital elderly; N=60 of this group No intervention. Sampling at timepoint 0 and for 50% of the group another sample at 3 months If respiratory symptoms develop in the 3 months after timepoint 0, participants are invited to provide a NPS/OPS to identify causative agent, and if one is established, individuals are sampled 3 more times at months 1, 3 and 5 post symptom onset
Frail elderly; N=60 of this group. Half with recurring respiratory infections, and half without No intervention. Sampling at timepoint 0 and for 50% of the group another sample at 3 months If respiratory symptoms develop in the 3 months after timepoint 0, participants are invited to provide a NPS/OPS to identify causative agent, and if one is established, individuals are sampled 3 more times at months 1, 3 and 5 post symptom onset

Outcome Measures

Primary Outcome Measures :

1. Frequency of nasal CD8+ T cells in young adults and frail older adults. [ Time Frame: baseline sample or month 3 sample ]
   CD8 T cells relative to nasal epithelial cells (ratio)

Secondary Outcome Measures :

1. 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. [ Time Frame: baseline sample or month 3 sample ]
   percentage of T cells and T cell subsets
2. 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. [ Time Frame: baseline sample or month 3 sample ]
   percentage of T cells responding to in vitro stimulations
3. 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. [ Time Frame: baseline sample or month 3 sample ]
   T cell clusters based on gene expression patterns
4. 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. [ Time Frame: baseline sample or month 3 sample ]
   Number and proportion of TCR clones
5. Stability of nasal T cells, as described for main study parameter, during a second sample after 3 months. [ Time Frame: baseline sample versus month 3 sample ]
   CD8 T cells relative to nasal epithelial cells (ratio)
6. Stability of nasal immune populations, during a second sample after 3 months. [ Time Frame: baseline sample versus month 3 sample ]
   immune cell populations relative to nasal epithelial cells (ratio)
7. Comparison of nasal immune cell populations between young adults, vital and frail elderly [ Time Frame: baseline sample or month 3 sample ]
   ratio to epithelial cells
8. Comparison of peripheral immune cell populations between young adults, vital and frail elderly [ Time Frame: baseline sample or month 3 sample ]
   percentage of total CD45+ cells
9. Concentration of nasal and systemic cytokines [ Time Frame: baseline sample or month 3 sample ]
   concentrations
10. Concentration of nasal and systemic metabolitesother immune populations [ Time Frame: baseline sample or month 3 sample ]
    concentrations
11. Respiratory tract microbiota profiles and their association with T cells and other immune parameters [ Time Frame: baseline sample or month 3 sample ]
    microbiota abundance (total sum scaling)
12. Presence of asymptomatic viral infections and their association with T cells and other immune parameters [ Time Frame: baseline sample or month 3 sample ]
    viral of loads (Ct)
13. Effect of sex on aging effects of nasal immune populations [ Time Frame: baseline sample or month 3 sample ]
    ratio to nasal epithelial cells
14. Effect of sex on aging effects of blood immune populations [ Time Frame: baseline sample or month 3 sample ]
    percentage of CD45+ cells
15. Frequencies of antigen-specific T cells in nose post infection. [ Time Frame: symptom onset and 1, 3 and 5 months later ]
    antigen-specific T cells as percentage of T cells
16. Frequencies of antigen-specific T cells in blood post infection. [ Time Frame: symptom onset and 1, 3 and 5 months later ]
    antigen-specific T cells as percentage of T cells

Biospecimen Retention:   Samples With DNA

Investigators will collect the following samples:

• peripheral blood
• nasopharyngeal swab
• oropharyngeal swab
• nasal curettes
• nasosorption

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes
• Sampling Method: Non-Probability Sample

Study Population

Study population: Investigators will recruit participants from 3 groups:

• healthy young adults (18-30 years, n=50)
• vital older adults (>65 years, n=60)
• frail elderly (>65 years, n=60). These will be consist of individuals without a history of recurrent respiratory infections or with >2 self-reported episodes of respiratory infection in the past year.

Frailty will be determined by a clinical frailty score. The Clinical Frailty Scale (CFS) is a scale that caretakers can use to identify level of frailty in older patients from 1 (very fit) through 9 (terminally ill). For the present study, "vital older patients" are defined as those with a CFS of 1-3 and "older patients living with frailty with a CFS of 4 or higher".

Criteria

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.

Contacts and Locations

Contacts

Contact: Simon P Jochems, PhD; +31715261328; s.p.jochems@lumc.nl

Locations

Netherlands

Leiden University Medical Center; Recruiting

Leiden, Zuid Holland, Netherlands, 2333ZA

Contact: Simon P Jochems, PhD +31715261328 s.p.jochems@lumc.nl

Sub-Investigator: Geert G Groeneveld, MD

Sub-Investigator: Simon M Mooijaart, MD

Sub-Investigator: Leo G Visser, MD

Sub-Investigator: Jutte JC de Vries, MD

Sub-Investigator: Hermelijn H Smits, PhD

Sponsors and Collaborators

Leiden University Medical Center

Investigators

• Principal Investigator: Simon P Jochems, PhD; LUMC

More Information

• Responsible Party: Simon P Jochems, PhD, Assistant professor, Leiden University Medical Center
• ClinicalTrials.gov Identifier: NCT06039527
• Other Study ID Numbers: P21.066; NL77841.058.21 ( Registry Identifier: toetsingonline.nl )
• First Posted: September 15, 2023
• Last Update Posted: December 15, 2023
• Last Verified: December 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• Plan Description: As even pseudonymized data is considered personal data as these can sometimes be traced back to an individual, data can be requested from the PI. If requests fall within the scope of the informed consent and study protocol, an MTA/DTA can be shared. Data will be posted on repositories with restricted access.

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Respiratory Tract Infections; Infections; Respiratory Tract Diseases