Clinical trial NCT05508321: Nasal Brushing for the Diagnosis and Understanding of Telomeropathies
Official title: Nasal Brushing for the Diagnosis and Understanding of Telomeropathies
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Telomere Disease
Telomere Shortening
Keywords: telomere
cellular senescence
smell
Lead sponsor: Cliniques universitaires Saint-Luc- Université Catholique de Louvain
Sponsor class: OTHER
First posted: 2022-08-19
Enrollment: 250
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Prospective interventional study
Primary purpose: DIAGNOSTIC

Brief summary: To date, the diagnosis of telomeropathies is based on telomere length measured in blood cells. However, this type of analysis is not always sufficient because some mutations underlying the development of telomeropathies are not associated with abnormal shortened telomeres. Since telomere dysfunction analysis cannot be performed on blood cells, it is mandatory to have access to another cellular material. To date, skin biopsies are performed to obtain fibroblasts. However, this technique is relatively invasive. The aim of this project is to assess whether nasal epithelial cells obtained through nasal brushing could offer the opportunity to detect cellular alterations and mutations involved in telomeropathies, in a mildly invasive way. If successful, this technique could become a non-invasive clinical tool for the diagnosis work-up of telomeropathies. Moreover, investigators aim to assess whether olfactory function is impaired in patients with telomeropathies.

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.

Eligibility criteria: 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

Primary outcomes:
measure: 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)
timeFrame: 5 minutes
Secondary outcomes:
measure: To develop primary cell cultures to study how the germline mutation affects telomere integrity in vitro through functional telomere assays
timeFrame: 5 minutes
Other outcomes:
measure: To assess whether patients with telomeropathies have impaired olfactory function
timeFrame: 20 minutes
Locations:
city: Bruxelles
country: Belgium
facility: Clinique Universitaires Saint-Luc
state: Woluwé-Saint-Lambert
Study officials:
affiliation: Cliniques universitaires Saint-Luc- Université Catholique de Louvain
name: Caroline Huart, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: