Frontotemporal Lobar DegenerationPROTEINOSKINNCT06490822
The Skin as a Window to the Central Nervous System in Frontotempolar Lombar Degeneration
A study testing Skin biopsy in people with Frontotemporal Lobar Degeneration, run by Nantes University Hospital at 1 site in France.
Trial 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… Read more about this study
- Who is it for?
- Ages 50 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Frontotemporal Lobar Degeneration
- What is being tested?
- Skin biopsy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 1 siteFrance
- Study dates
- 17 Dec 2024to Jul 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Show all 20Show fewer
- Aged 50-75 years Paired to at least one patient on age (less or more 5 years)
- MOCA ≥ 26
- Membership of social security scheme
- Non inclusion Criteria (Patients and healthy volunteers):
- 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
- Inability to sign an informed consent
- Non inclusion criteria (Patients) • Patient with neurological disease other than FTLD
- Non inclusion criteria (Healthy volunteers) :
- Evidence of neurological disorder at the inclusion including but not limted to FTLD, Parkinson disease, Alzheimer disease, lewy body dementia, Huntington disease, systemic lupus erythematosus multiple sclerosis; learning disabilities, mental retardation, severe hypoxic brain injuries, brain trauma with permanent cognitive impairments.
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Claire BOUTOLEAU-BRETONNIERE, MD contact
France1 site, 1 recruiting
- Recruiting
Nantes University Hospital
Nantes, 44093
Claire BOUTOLEAU BRETONNIERE, MD, 02 40 16 54 22 ext. +33
Claire BOUTOLEAU BRETONNIERE
About this study
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.
Read more
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.
Read the detailed description
Participant with Frontotemporal Lobar degeneration equally distributed into behavioral variant of frontotemporal dementia (bvFTD), language variant with primary progressive aphasia (PPA) and motor presentations with atypical parkinsonian disorders (corticobasal degeneration-CBD and progressive supranuclear palsy-PSP) and motoneuron disorder (amyotrophic lateral sclerosis -ALS) will be included at Nantes University Hospital during a period of 24 months.
Healthy volunteers will be included as comparative group. A skin biopsy and venous blood samples will be collected for all participants.
- Conditions
- Frontotemporal Lobar Degeneration
- Being tested
- Skin biopsy
- Keywords
- FTLD, tau, TDP43, skin biopsy
- Medical subject headings
- Frontotemporal Lobar Degeneration, Pick Disease of the Brain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Skin biopsyProcedure or surgery
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
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Procedure: Skin biopsy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Amount of TDP 43
assessed by Western blot and qPCR to determine level of expression of TDP-43 in the skin
Measured: 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
Measured: Day of inclusion
Secondary outcomes (5)
Amount of Tau phosphorylation
phospho-tau/tau ratio in the skin will be measured by Western blot
Measured: Day of inclusion
Amount of TDP 43 phosphorylation
phospho-TDP-43 /TDP43 ratio in the skin will be measured by Western blot
Measured: Day of inclusion
Neuropsychological characterization
During their follow-up FTLD patients underwent a complete neuropsycological assessment define as:
- mini-mental state examination (MMSE)
- the 16-item Free Recall/Indicated Recall test (RL/RI-16 items)
- Rey figure and recall
- Trail Making Test (TMT A \& B)
- Wechsler Adult Intelligence Scale
- Literal (letter P) and categorical (animals) fluency
- Rapid Frontal Efficiency Battery (BREF)
- Wisconsin Card Sorting Test (WCST)
- Zoo test of Behavioural Assessment of the Dysexecutive Syndrome (BADS)
- Stroop test - 4 boards
- Oral image naming test (DO 80)
- Theory of mind (ToM-15)
- ekman facial emotion recognition test
Measured: 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
The 10-items scale Daphne will be used to explore disinhibition (4 items), apathy(1 item), perseveration (1 item), hyperorality (2items), personal neglect (1 item) and loss of empathy (1 item)
Measured: 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
Mutation carrier patient will be identified among participant (not all the participant) who had a genetic screening had neen carried out during their follow up.
Measured: before inclusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jul 2024
- Study start17 Dec 2024
- Primary completionDec 2026 (estimated)
- Study completionJul 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Frontotemporal Lobar DegenerationStudies of the same condition, open and under way.
- More trials run by Nantes University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Nantes University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06490822
- Sponsor's protocol ID
- RC23_0575
- Acronym
- PROTEINOSKIN
- Status last verified
- Dec 2024
- First submitted
- 25 Jun 2024
- Last updated
- 20 Dec 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Skin as a Window to the Central Nervous System in Frontotempolar Lombar Degeneration
- ClinicalTrials.gov ID
- NCT06490822
- Acronym / sponsor ID
- PROTEINOSKIN / RC23_0575
- Conditions
- Frontotemporal Lobar Degeneration
- Keywords
- FTLD, tau, TDP43, skin biopsy
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- Nantes University HospitalUniversity, hospital or other
- Study start
- 17 Dec 2024 (actual)
- Primary completion
- Dec 2026 (estimated)
- Study completion
- Jul 2027 (estimated)
- First posted
- 8 Jul 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Participant with Frontotemporal Lobar degeneration equally distributed into behavioral variant of frontotemporal dementia (bvFTD), language variant with primary progressive aphasia (PPA) and motor presentations with atypical parkinsonian disorders (corticobasal degeneration-CBD and progressive supranuclear palsy-PSP) and motoneuron disorder (amyotrophic lateral sclerosis -ALS) will be included at Nantes University Hospital during a period of 24 months.
Healthy volunteers will be included as comparative group. A skin biopsy and venous blood samples will be collected for all participants.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Single arm study | Other | Procedure: Skin biopsyA 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 |
Who may qualify
- Ages
- 50 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- 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
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Skin biopsyA 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 or surgery | Single arm study |
Primary outcome
Amount of TDP 43
Time frame: Day of inclusion
assessed by Western blot and qPCR to determine level of expression of TDP-43 in the skin
Amount of Tau assessed by Western blot and qPCR
Time frame: Day of inclusion
assessed by Western blot and qPCR to determine level of expression of Tau in the skin
5 secondary outcomes
Amount of Tau phosphorylation
Time frame: Day of inclusion
Amount of TDP 43 phosphorylation
Time frame: Day of inclusion
Neuropsychological characterization
Time frame: 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
Time frame: 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
Time frame: before inclusion
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Dec 2024.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Claire BOUTOLEAU-BRETONNIERE, MD contact
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Skin biopsy in people with Frontotemporal Lobar Degeneration, run by Nantes University Hospital at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 20 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 20 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Claire BOUTOLEAU-BRETONNIERE, MD (02 40 16 54 22 ext. +33, claire.boutoleaubretonnière@chu-nantes.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Amount of TDP 43 (time frame: Day of inclusion). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Dec 2024.