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

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

Tracking Information
First Submitted Date September 1, 2023
First Posted Date September 15, 2023
Last Update Posted Date December 15, 2023
Actual Study Start Date January 24, 2021
Estimated Primary Completion Date May 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: September 8, 2023)		 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)
Original Primary Outcome Measures Same as current
Change History
Current Secondary Outcome Measures
 (submitted: December 11, 2023)
  • 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
  • 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
  • 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
  • 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
  • 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)
  • 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)
  • 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
  • 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
  • Concentration of nasal and systemic cytokines [ Time Frame: baseline sample or month 3 sample ]
    concentrations
  • Concentration of nasal and systemic metabolitesother immune populations [ Time Frame: baseline sample or month 3 sample ]
    concentrations
  • 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)
  • 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)
  • Effect of sex on aging effects of nasal immune populations [ Time Frame: baseline sample or month 3 sample ]
    ratio to nasal epithelial cells
  • Effect of sex on aging effects of blood immune populations [ Time Frame: baseline sample or month 3 sample ]
    percentage of CD45+ cells
  • 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
  • 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
Original Secondary Outcome Measures
 (submitted: September 8, 2023)
  • 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
  • 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
  • Transcriptomic state 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 ]
    T cell clusters based on gene expression patterns
  • 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
  • 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)
  • 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)
  • 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
  • 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
  • Concentration of nasal and systemic factors (e.g. cytokines and metabolites) and their association with T cells and other immune populations [ Time Frame: baseline sample or month 3 sample ]
    concentrations
  • 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)
  • 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)
  • Effect of sex on aging effects of nasal immune populations [ Time Frame: baseline sample or month 3 sample ]
    ratio to nasal epithelial cells
  • Effect of sex on aging effects of blood immune populations [ Time Frame: baseline sample or month 3 sample ]
    percentage of CD45+ cells
  • 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
  • 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
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title TINO: T Cells in the Nose of Older Adults
Official Title TINO: Identifying the Underlying Mechanisms and Consequences of the Loss of Nasal T Cells in Vital and Frail Older Individuals
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.
Detailed Description Not Provided
Study Type Observational
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples With DNA
Description:

Investigators will collect the following samples:

  • peripheral blood
  • nasopharyngeal swab
  • oropharyngeal swab
  • nasal curettes
  • nasosorption
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".
Condition
  • Respiratory Tract Infections
  • Aging
Intervention Not Provided
Study Groups/Cohorts
  • 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
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 Recruiting
Estimated Enrollment
 (submitted: September 8, 2023)		 170
Original Estimated Enrollment Same as current
Estimated Study Completion Date July 2024
Estimated Primary Completion Date May 2024   (Final data collection date for primary outcome measure)
Eligibility 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.
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers Yes
Contacts
Contact: Simon P Jochems, PhD +31715261328 s.p.jochems@lumc.nl
Listed Location Countries Netherlands
Removed Location Countries  
 
Administrative Information
NCT Number NCT06039527
Other Study ID Numbers P21.066
NL77841.058.21 ( Registry Identifier: toetsingonline.nl )
Has Data Monitoring Committee No
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
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.
Current Responsible Party Simon P Jochems, PhD, Leiden University Medical Center
Original Responsible Party Same as current
Current Study Sponsor Leiden University Medical Center
Original Study Sponsor Same as current
Collaborators Not Provided
Investigators
Principal Investigator: Simon P Jochems, PhD LUMC
PRS Account Leiden University Medical Center
Verification Date December 2023