Nasal Brushing for the Diagnosis and Understanding of Telomeropathies (TELOSTIC)
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Endpoint #1: To assess the suitability of nasal brushing analyses for the diagnosis of telomeropathies.
To date, the complete diagnosis of telomeropathies, including the identification of responsible mutations, is based on blood samples and fibroblast cultures obtained through skin biopsies. Cells obtained through nasal brushing offer the opportunity to detect cellular alterations and mutations involved in telomeropathies, in a mildly invasive way. Investigators will thus assess a population of patients with a suspicion of telomeropathy, using a nasal brushing, and will compare their nasal brushing results to those of age-matched healthy controls. In patients, results of nasal brushing will be compared to standard of care blood test (leukocyte telomere length using Flow-FISH technique). If investigators confirm that the nasal brushing offers the opportunity to i) detect damaged telomeres and premature cellular senescence and ii) identify mutations related to telomeropathies, this technique could become a non-invasive clinical tool for the diagnosis work-up of telomeropathies.
Endpoint #2: To develop primary cell cultures for the functional study of new germline mutations.
To date, various germline mutations have already been identified in telomeropathy patients, in a total of 17 genes. Understanding how these mutations were affecting telomere biology relied on in vitro studies with either patient-derived fibroblasts or engineered human cell lines recapitulating the mutation. This was a mandatory step towards the molecular understanding of these pathologies. Because olfactory neural precursors have the capacity to grow in culture, this offers the additional possibility to perform functional studies on primary cultures of nasal brushing-derived cells for novel mutations, with still unknown impact on telomeres, that would be identified. Again, this could advantageously replace patients' fibroblast cultures established through skin biopsy.
Endpoint #3: To evaluate whether patients with telomeropathies have impaired olfactory function.
Olfactory function is decreased in several diseases and is increasingly recognized as an indicator of biological aging. To date, no data exist regarding the impact of telomeropathies on olfactory function. Therefore, investigators aim to psychophysically assess olfactory function in patients with telomeropathies, in comparison to age-matched healthy controls.
Study Type
Enrollment (Anticipated)
Phase
- Not Applicable
Contacts and Locations
Study Contact
- Name: Caroline Huart, MD, PhD
- Phone Number: +3227646005
- Email: caroline.huart@saintluc.uclouvain.be
Study Contact Backup
- Name: Anabelle Decottignies, PhD
- Phone Number: +3227647574
- Email: anabelle.decottignies@uclouvain.be
Study Locations
-
-
Woluwé-Saint-Lambert
-
Bruxelles, Woluwé-Saint-Lambert, Belgium, 1200
- Recruiting
- Clinique Universitaires Saint-Luc
-
Contact:
- Caroline Huart, MD, PhD
- Phone Number: +3227646005
- Email: caroline.huart@saintluc.uclouvain.be
-
Contact:
- Anabelle Decottignies, PhD
- Phone Number: +3227647574
- Email: anabelle.decottignies@uclouvain.be
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- ADULT
- OLDER_ADULT
- CHILD
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Patients : Having a suspicion of or a confirmed telomeropathy
Exclusion Criteria:
Patients and controls:No access to the olfactory cleft Patients and controls: Abnormal endoscopic finding (i.e. meningocele, vascular ectasia)
Specific exclusion criteria for smell assessment (outcome 3):
Patients and controls: History of neurological or psychiatric disorder known to interfere with olfactory function or olfactory trouble (postinfectious, posttraumatic, toxic) Patients and controls: History of chronic rhinosinusitis
Study Plan
How is the study designed?
Design Details
- Primary Purpose: DIAGNOSTIC
- Allocation: NON_RANDOMIZED
- Interventional Model: PARALLEL
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
EXPERIMENTAL: Patients with confirmed or suspected telomeropathy
Patients with idiopathic pulmonary fibrosis, adult or pediatric medullar dysplasia or myelodysplasia, unexplained liver cirrhosis or unexplained liver regenerative nodular hyperplasia.
|
Nasal brushing to harvest nasal cells and perform staining experiments
Assessment of olfactory function
|
|
OTHER: Controls
Age and sex-matched control participants
|
Nasal brushing to harvest nasal cells and perform staining experiments
Assessment of olfactory function
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
To assess the suitability of nasal brushing analysis for the diagnosis of telomeropathies through evaluation of cellular senescence (SA-B-gal activity) and damaged telomeres (FISH/IF)
Time Frame: 5 minutes
|
Investigators will evaluate if it is possible to detect damaged telomeres (via FISH/IF - Fluorescence In Situ Hybridation /ImmunoFluoresence -) and premature cellular senescence in patients (via SA-B-gal activity - Senescence Associated Beta-galactosidase activity measurement - and senescence associated biomarkers by qRT-PCR - quantitative Reverse Transcription - Polymerase Chain Reaction - ), in comparison to healthy controls.
|
5 minutes
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
To develop primary cell cultures to study how the germline mutation affects telomere integrity in vitro through functional telomere assays
Time Frame: 5 minutes
|
Cells harvested from the nasal mucosa will be cultived and analysed to detect telomeric DNA damage and premature cellular senescence
|
5 minutes
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
To assess whether patients with telomeropathies have impaired olfactory function
Time Frame: 20 minutes
|
Olfactory function will be assessed using the validated Sniffin' Sticks test
|
20 minutes
|
Collaborators and Investigators
Investigators
- Principal Investigator: Caroline Huart, MD, PhD, Cliniques Universitaires Saint-Luc
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ANTICIPATED)
Study Completion (ANTICIPATED)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ACTUAL)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Other Study ID Numbers
- 2022/07FEV/046
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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