The Skin as a Window to the Central Nervous System in Frontotempolar Lombar Degeneration

NCT06490822 | Recruiting

• 1 other identifier: RC23_0575
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

Frontotemporal lobar degeneration (FTLD) is a clinically heterogeneous syndrome, characterized by progressive decline in behaviour and/or language. From a pathological standpoint, like the great majority of neurodegenerative disorders, FTLD are proteinopathies, which are characterized by the presence of specific protein deposits in the Central Nervous System (CNS). Accordingly, the two main deposits observed in FTLD are either made of Tau or transactive response DNA binding protein 43 (TDP-43). In pathological conditions such as FTLD, both proteins are aggregated and hyperphosphorylated. It is now well established that the pathological process in some proteinopathies such as synucleinopathies (of which Parkinson's disease is the main representative) is not limited to the brain but also widespread throughout the peripheral autonomic networks, including the autonomic innervation of the skin. In this context, many independent studies have shown that the pathological process in PD could be detected using routine punch skin biopsies opening the way for the development of original histopathological markers of the disease. Our hypothesis is that such a scenario could also occur in FTLDs and that the detection of the pathological tau or TDP-43 protein in the skin could help in diagnosing FTLD. This is especially relevant as, despite the recent progress in genetics, neurobiology and neuroimaging, there are no available biomarkers for FTLD.

Conditions

Frontotemporal Lobar Degeneration

Keywords

FTLD; tau; TDP43; skin biopsy

Outcome Measures

Primary Outcomes (2)

• Amount of TDP 43

  assessed by Western blot and qPCR to determine level of expression of TDP-43 in the skin

  Day of inclusion

• Amount of Tau assessed by Western blot and qPCR

  assessed by Western blot and qPCR to determine level of expression of Tau in the skin

  Day of inclusion

Secondary Outcomes (5)

• Amount of Tau phosphorylation

  Day of inclusion

• Amount of TDP 43 phosphorylation

  Day of inclusion

• Neuropsychological characterization

  day of inclusion for patients vFTD, PPA and corticobasal degeneration-CBD and progressive supranuclear palsy-PSP within 12 months of inclusion for patients ALS

• Behaviour profile

  day of inclusion for patients vFTD, PPA and corticobasal degeneration-CBD and progressive supranuclear palsy-PSP within 12 months of inclusion for patients ALS

• FTLD mutation

  before inclusion

Study Arms (1)

Single arm study

OTHER

A single 3 mm-diameter punch skin biopsy will be obtained from FTLD patients and healthy volunteers at the C8 paravertebral under local anesthesia to analyze cutaneous innervation

Procedure: Skin biopsy

Interventions

Skin biopsy PROCEDURE

A single 3 mm-diameter punch skin biopsy will be obtained from FTLD patients and healthy volunteers at the C8 paravertebral under local anesthesia to analyze cutaneous innervation

Single arm study

Eligibility Criteria

• Age: 50 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adressed or followed at memory clinic or ALS expert center at Nantes university hospital.
• Aged 50-75 years
• Fulfilling current diagnosis criteria for one of the disorder: vcfFTD, non-Alzheimer PPA (semantic or non fluent), DCB or PSP,ALS
• MMSE ≥ 18
• Membership of social security scheme
• No history of neurological disease, diabetes, or alteration/damage of peripheral nervous system
• Aged 50-75 years Paired to at least one patient on age (less or more 5 years)
• MOCA ≥ 26
• Membership of social security scheme
• Concomitting conditions affecting the peripheral nervous system such as but not limited to diabetes, renal failure, thyroid disorder, vitamin B12 deficiency, acute and chronic inflammatory diseases HIV, syphilis
• Know allergy to local anesthetic
• Known coagulopathy
• Pregnant women or breastfeeding women
• Person under court protection sous sauvegarde de justice
• Person under guardianship

Sponsors & Collaborators

• Nantes University Hospital: lead

Study Sites (1)

Nantes University Hospital

Nantes, 44093, France

RECRUITING

MeSH Terms

Conditions

Frontotemporal Lobar Degeneration; Pick Disease of the Brain

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; TDP-43 Proteinopathies; Neurodegenerative Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases; Neurocognitive Disorders; Mental Disorders; Frontotemporal Dementia

Central Study Contacts

Claire BOUTOLEAU-BRETONNIERE, MD

CONTACT

02 40 16 54 22; claire.boutoleaubretonnière@chu-nantes.fr

pascal DERKINDEREN, Pr

CONTACT

02 40 16 54 22; derkinderenp@yahoo.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 25, 2024
• First Posted: July 8, 2024
• Study Start: December 17, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): July 1, 2027
• Last Updated: December 20, 2024

Record last verified: 2024-12

Locations

FR (1)