Alzheimer DiseaseNCT06528964
Proteinopathies Expression in Skin of Neurodegenerative Disorders
An observational study of Alzheimer Disease and Frontotemporal Dementia, run by Universidad Autonoma de San Luis Potosí at 1 site in Mexico.
Trial summary
The goal of this observational study is to compare the aggregation pattern of proteinopathies (alpha-synuclein, amyloid-beta, phosphorylated tau and transactive response DNA -binding protein 43 [TDP43]) in skin biopsies of patients with a neurodegenerative disease like Alzheimer's disease, frontotemporal lobe… Read more about this study
- Who is it for?
- Ages 45 years and olderHealthy volunteers can take part
- Conditions the study is for
- Alzheimer Disease, Frontotemporal Dementia, Parkinson Disease
- What is being tested?
- Immunohistochemistry and immunofluorescence
- How many people
- 40 participants
- Where
- 1 siteMexico
- Study dates
- 20 Dec 2023to 1 Nov 2026
- Phase
- Observational
- 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 45 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: The patients and controls that meet the eligibility criteria will be recruited from the neurology department consult from the Hospital Central Dr Ignacio Morones Prieto
Who may be able to join
- Patients 45 years and older
- Men and women
- Patients diagnosed with Alzheimer's disease, frontotemporal lobe dementia, Parkinson's disease, atypical Parkinsonism, amyotrophic lateral sclerosis or normal pressure hydrocephalus
- Patients that voluntarily accept to participate in the study and accept the consent form
- People 45 years and older
- Men and women
Show all 10Show fewer
- Subjects can be related to a patient but not by blood (for example spouse of a patient)
- Subjects don't have direct family history of a neurodegenerative control
- Subjects don't have any clinical findings suggesting dementia
- Subjects voluntarily accept to participate in the study and accept the consent form
Who cannot join
- Patients or controls that have a personal history of cerebrovascular disease, psychiatric disease, post traumatic dementia or HIV related dementia
- Patients in which the diagnosis is not clear or hasn't been confirmed
- Patients or controls that have a neuroinfection
- Patients or controls that a diagnosed skin disease
- Patients that have an "atypical" presentation of the disease
- Patients or controls that have diagnosis of a coagulopathy
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Cristina Monzón Tapia, MD contact
Mexico1 site, 1 recruiting
- Recruiting
Hospital Central Dr. Ignacio Morones Prieto
San Luis Potosí City, 78290
Ildefonso Rodríguez-Leyva, MD PhD, +52 444 834 2739, ilrole@yahoo.com.mx
Cristina Monzón Tapia, MD, +52 444 834 2739, a267473@alumnos.uaslp.mx
About this study
Official title: Expression of Proteinopathies in Skin Biopsies of Patients With Neurodegenerative Disorders
The goal of this observational study is to compare the aggregation pattern of proteinopathies (alpha-synuclein, amyloid-beta, phosphorylated tau and transactive response DNA -binding protein 43 [TDP43]) in skin biopsies of patients with a neurodegenerative disease like Alzheimer's disease, frontotemporal lobe dementia, Parkinson's disease, atypical Parkinsonism, amyotrophic lateral sclerosis or normal pressure hydrocephalus. The main question it aims to answer is:
- Is there a specific pattern of aggregation of proteinopathies in skin biopsies in each neurodegenerative disease in comparison to healthy control subjects?
Skin biopsies will be analyzed using immunohistochemistry and immunofluorescence for detection of alpha-synuclein, amyloid-beta, phosphorylated tau and TAR DNA binding protein 43, and the aggregation patterns will be compared between patients with a neurodegenerative disease vs patient with normal pressure hydrocephalus vs healthy control subjects.
Read the detailed description
Alzheimer's disease is the main cause of neurodegenerative dementia and represents a high degree of morbidity and mortality among the patients who have it, causing a great economic impact in health systems. In general population the second cause of neurodegenerative dementia is frontotemporal lobe dementia and it's also the first cause of dementia in patients under 65 years old.
Neurodegenerative diseases have been associated with the deposit of abnormal aggregated proteins like alpha-synuclein, amyloid-beta, phosphorylated tau and TAR DNA binding protein 43 in brain tissue. Similar deposits of a-synuclein, p-TAU and TDP-43 have been identified through immunohistochemistry and immunofluorescence in skin biopsies.
Main objective: Compare the aggregation pattern between the different proteinopathies (a-synuclein, amyloid-b, p-TAU and TDP-43) with immunohistochemistry in skin biopsies of patients with Alzheimer's disease, frontotemporal lobe dementia, Parkinson's disease, atypical Parkinsonism, amyotrophic lateral sclerosis and normal pressure hydrocephalus vs control subjects.
Study design: this will be an observational, transversal and comparative analysis study. Inclusion criteria: patients, men and women, 45 and older diagnosed with Alzheimer's disease, frontotemporal lobe dementia, Parkinson's disease, atypical Parkinsonism, amyotrophic lateral sclerosis or normal pressure hydrocephalus will be recruited for sampling with skin biopsy. Healthy control subjects will be men or women similar in age to the patients that don't have any personal or family history of a neurodegenerative disease and that are not related by blood to the patients in this study.
Sample size calculation and statistical analysis:
All the patients that meet the inclusion criteria and accept the consent form, from the neurology department of Hospital Central Dr Ignacio Morones Prieto, will be recruited for one year.
A descriptive analysis will be carried out with frequencies and percentages for categorical variables, for continuous variables central tendency and dispersion analysis, the normality of the data will be evaluated using the Kolmogorov-Smirnov or Shapiro-Wilk test as appropriate. In case the data ha a normal distribution, it will be analyzed with the ANOVA test followed by Tukey and in the case the data doesn't have a normal distribution the analysis will be made with Kruskal Wallis followed by Mann Whitney U.
- Conditions
- Alzheimer Disease, Frontotemporal Dementia, Parkinson Disease, Atypical Parkinsonism, Amyotrophic Lateral Sclerosis, Normal Pressure Hydrocephalus
- Being tested
- Immunohistochemistry and immunofluorescence
- Keywords
- Alpha Synuclein Pathology, Tauopathies, TDP-43 Proteinopathies, Beta-Amyloid
- Medical subject headings
- Alzheimer Disease, Frontotemporal Dementia, Parkinson Disease, Amyotrophic Lateral Sclerosis, Hydrocephalus, Normal Pressure, Synucleinopathies, Tauopathies, TDP-43 Proteinopathies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Immunohistochemistry and immunofluorescenceDiagnostic test
Skin biopsies will be analyzed using immunohistochemistry and immunofluorescence to detect the presence of aggregated a-synuclein, amyloid-b, p-TAU and TDP-43.
| Study group | Role | What they receive |
|---|---|---|
| Patients with neurodegenerative disease | Patients diagnosed with either Alzheimer's disease, frontotemporal lobe dementia, Parkinson's disease, atypical Parkinsonism or amyotrophic lateral sclerosis. Receives: Diagnostic Test: Immunohistochemistry and immunofluorescence | |
| Patients with normal pressure hydrocephalus | Patients diagnosed with normal pressure hydrocephalus, because of their clinical presentation (acute or subacute gait abnormalities, memory loss or personality changes and urinary incontinence) with radiological confirmation of ventriculomegaly and normal cerebrospinal fluid opening pressure. Receives: Diagnostic Test: Immunohistochemistry and immunofluorescence | |
| Healthy control subjects | Person, men or women, above 45 years old, that don't have history of family or personal neurodegenerative disease. Receives: Diagnostic Test: Immunohistochemistry and immunofluorescence |
What is being measured
The primary outcome is the main question the study is designed to answer.
Aggregation pattern of a-synuclein, amyloid-b, p-TAU and TDP-43
The detection of each proteinopathy will be compared between each of them in every patient and compared to healthy control subjects.
Measured: Each patient will be recruited and sampled the same day of the evaluation which will take about 1 hour. The final report it takes a frame time around two years.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jul 2024
- Study start20 Dec 2023
- Primary completion25 Oct 2026 (estimated)
- Study completion1 Nov 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Alzheimer DiseaseStudies of the same condition, open and under way.
- 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
- Observational
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Universidad Autonoma de San Luis Potosí
- Sponsor type
- University, hospital or other
- Collaborators
- Hospital Central "Dr. Ignacio Morones Prieto"
- Responsible party
- Principal investigator, Ildefonso Rodriguez-Leyva, Universidad Autonoma de San Luis Potosí
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06528964
- Sponsor's protocol ID
- 42-23
- Status last verified
- Dec 2024
- First submitted
- 25 Jul 2024
- Last updated
- 16 Dec 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Said HM, Kaya D, Yavuz I, Dost FS, Altun ZS, Isik AT. A Comparison of Cerebrospinal Fluid Beta-Amyloid and Tau in Idiopathic Normal Pressure Hydrocephalus and Neurodegenerative Dementias. Clin Interv Aging. 2022 Apr 11;17:467-477. doi: 10.2147/CIA.S360736. eCollection 2022.
PubMed 35431542Espay AJ, Da Prat GA, Dwivedi AK, Rodriguez-Porcel F, Vaughan JE, Rosso M, Devoto JL, Duker AP, Masellis M, Smith CD, Mandybur GT, Merola A, Lang AE. Deconstructing normal pressure hydrocephalus: Ventriculomegaly as early sign of neurodegeneration. Ann Neurol. 2017 Oct;82(4):503-513. doi: 10.1002/ana.25046. Epub 2017 Oct 4.
PubMed 28892572Castanedo-Cazares JP, Rodriguez-Leyva I. Skin biomarkers for neurodegenerative disease: a future perspective. Neurodegener Dis Manag. 2015 Dec;5(6):465-7. doi: 10.2217/nmt.15.51. Epub 2015 Nov 30. No abstract available.
PubMed 26619251Rodriguez-Leyva I, Chi-Ahumada EG, Carrizales J, Rodriguez-Violante M, Velazquez-Osuna S, Medina-Mier V, Martel-Gallegos MG, Zarazua S, Enriquez-Macias L, Castro A, Calderon-Garciduenas AL, Jimenez-Capdeville ME. Parkinson disease and progressive supranuclear palsy: protein expression in skin. Ann Clin Transl Neurol. 2016 Feb 1;3(3):191-9. doi: 10.1002/acn3.285. eCollection 2016 Mar.
PubMed 27042679Golde TE, Borchelt DR, Giasson BI, Lewis J. Thinking laterally about neurodegenerative proteinopathies. J Clin Invest. 2013 May;123(5):1847-55. doi: 10.1172/JCI66029. Epub 2013 May 1.
PubMed 23635781
Study at a glance
From the registry record, last updated by the sponsor on 16 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Expression of Proteinopathies in Skin Biopsies of Patients With Neurodegenerative Disorders
- ClinicalTrials.gov ID
- NCT06528964
- Acronym / sponsor ID
- 42-23
- Conditions
- Alzheimer Disease, Frontotemporal Dementia, Parkinson Disease, Atypical Parkinsonism, Amyotrophic Lateral Sclerosis, Normal Pressure Hydrocephalus
- Keywords
- Alpha Synuclein Pathology, Tauopathies, TDP-43 Proteinopathies, Beta-Amyloid
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Universidad Autonoma de San Luis PotosíUniversity, hospital or other
- Collaborators
- Hospital Central "Dr. Ignacio Morones Prieto"
- Study start
- 20 Dec 2023 (actual)
- Primary completion
- 25 Oct 2026 (estimated)
- Study completion
- 1 Nov 2026 (estimated)
- First posted
- 30 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.
The goal of this observational study is to compare the aggregation pattern of proteinopathies (alpha-synuclein, amyloid-beta, phosphorylated tau and transactive response DNA -binding protein 43 [TDP43]) in skin biopsies of patients with a neurodegenerative disease like Alzheimer's disease, frontotemporal lobe dementia, Parkinson's disease, atypical Parkinsonism, amyotrophic lateral sclerosis or normal pressure hydrocephalus. The main question it aims to answer is:
- Is there a specific pattern of aggregation of proteinopathies in skin biopsies in each neurodegenerative disease in comparison to healthy control subjects?
Skin biopsies will be analyzed using immunohistochemistry and immunofluorescence for detection of alpha-synuclein, amyloid-beta, phosphorylated tau and TAR DNA binding protein 43, and the aggregation patterns will be compared between patients with a neurodegenerative disease vs patient with normal pressure hydrocephalus vs healthy control subjects.
Detailed description
Alzheimer's disease is the main cause of neurodegenerative dementia and represents a high degree of morbidity and mortality among the patients who have it, causing a great economic impact in health systems. In general population the second cause of neurodegenerative dementia is frontotemporal lobe dementia and it's also the first cause of dementia in patients under 65 years old.
Neurodegenerative diseases have been associated with the deposit of abnormal aggregated proteins like alpha-synuclein, amyloid-beta, phosphorylated tau and TAR DNA binding protein 43 in brain tissue. Similar deposits of a-synuclein, p-TAU and TDP-43 have been identified through immunohistochemistry and immunofluorescence in skin biopsies.
Main objective: Compare the aggregation pattern between the different proteinopathies (a-synuclein, amyloid-b, p-TAU and TDP-43) with immunohistochemistry in skin biopsies of patients with Alzheimer's disease, frontotemporal lobe dementia, Parkinson's disease, atypical Parkinsonism, amyotrophic lateral sclerosis and normal pressure hydrocephalus vs control subjects.
Study design: this will be an observational, transversal and comparative analysis study. Inclusion criteria: patients, men and women, 45 and older diagnosed with Alzheimer's disease, frontotemporal lobe dementia, Parkinson's disease, atypical Parkinsonism, amyotrophic lateral sclerosis or normal pressure hydrocephalus will be recruited for sampling with skin biopsy. Healthy control subjects will be men or women similar in age to the patients that don't have any personal or family history of a neurodegenerative disease and that are not related by blood to the patients in this study.
Sample size calculation and statistical analysis:
All the patients that meet the inclusion criteria and accept the consent form, from the neurology department of Hospital Central Dr Ignacio Morones Prieto, will be recruited for one year.
A descriptive analysis will be carried out with frequencies and percentages for categorical variables, for continuous variables central tendency and dispersion analysis, the normality of the data will be evaluated using the Kolmogorov-Smirnov or Shapiro-Wilk test as appropriate. In case the data ha a normal distribution, it will be analyzed with the ANOVA test followed by Tukey and in the case the data doesn't have a normal distribution the analysis will be made with Kruskal Wallis followed by Mann Whitney U.
Study design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Patients with neurodegenerative disease | – | Diagnostic Test: Immunohistochemistry and immunofluorescencePatients diagnosed with either Alzheimer's disease, frontotemporal lobe dementia, Parkinson's disease, atypical Parkinsonism or amyotrophic lateral sclerosis. |
| Patients with normal pressure hydrocephalus | – | Diagnostic Test: Immunohistochemistry and immunofluorescencePatients diagnosed with normal pressure hydrocephalus, because of their clinical presentation (acute or subacute gait abnormalities, memory loss or personality changes and urinary incontinence) with radiological confirmation of ventriculomegaly and normal cerebrospinal fluid opening pressure. |
| Healthy control subjects | – | Diagnostic Test: Immunohistochemistry and immunofluorescencePerson, men or women, above 45 years old, that don't have history of family or personal neurodegenerative disease. |
Who may qualify
- Ages
- 45 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- The patients and controls that meet the eligibility criteria will be recruited from the neurology department consult from the Hospital Central Dr Ignacio Morones Prieto
Key inclusion criteria (10 listed)
- Patients 45 years and older
- Men and women
- Patients diagnosed with Alzheimer's disease, frontotemporal lobe dementia, Parkinson's disease, atypical Parkinsonism, amyotrophic lateral sclerosis or normal pressure hydrocephalus
- Patients that voluntarily accept to participate in the study and accept the consent form
- People 45 years and older
Key exclusion criteria (6 listed)
- Patients or controls that have a personal history of cerebrovascular disease, psychiatric disease, post traumatic dementia or HIV related dementia
- Patients in which the diagnosis is not clear or hasn't been confirmed
- Patients or controls that have a neuroinfection
- Patients or controls that a diagnosed skin disease
- Patients that have an "atypical" presentation of the disease
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 |
|---|---|---|
| Immunohistochemistry and immunofluorescenceSkin biopsies will be analyzed using immunohistochemistry and immunofluorescence to detect the presence of aggregated a-synuclein, amyloid-b, p-TAU and TDP-43. | Diagnostic test | Healthy control subjects, Patients with neurodegenerative disease, Patients with normal pressure hydrocephalus |
Primary outcome
Aggregation pattern of a-synuclein, amyloid-b, p-TAU and TDP-43
Time frame: Each patient will be recruited and sampled the same day of the evaluation which will take about 1 hour. The final report it takes a frame time around two years.
The detection of each proteinopathy will be compared between each of them in every patient and compared to healthy control subjects.
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 16 Dec 2024.
- Background: PubMed 35431542Said HM, Kaya D, Yavuz I, Dost FS, Altun ZS, Isik AT. A Comparison of Cerebrospinal Fluid Beta-Amyloid and Tau in Idiopathic Normal Pressure Hydrocephalus and Neurodegenerative Dementias. Clin Interv Aging. 2022 Apr 11;17:467-477. doi: 10.2147/CIA.S360736. eCollection 2022.
- Background: PubMed 28892572Espay AJ, Da Prat GA, Dwivedi AK, Rodriguez-Porcel F, Vaughan JE, Rosso M, Devoto JL, Duker AP, Masellis M, Smith CD, Mandybur GT, Merola A, Lang AE. Deconstructing normal pressure hydrocephalus: Ventriculomegaly as early sign of neurodegeneration. Ann Neurol. 2017 Oct;82(4):503-513. doi: 10.1002/ana.25046. Epub 2017 Oct 4.
- Background: PubMed 26619251Castanedo-Cazares JP, Rodriguez-Leyva I. Skin biomarkers for neurodegenerative disease: a future perspective. Neurodegener Dis Manag. 2015 Dec;5(6):465-7. doi: 10.2217/nmt.15.51. Epub 2015 Nov 30. No abstract available.
- Background: PubMed 27042679Rodriguez-Leyva I, Chi-Ahumada EG, Carrizales J, Rodriguez-Violante M, Velazquez-Osuna S, Medina-Mier V, Martel-Gallegos MG, Zarazua S, Enriquez-Macias L, Castro A, Calderon-Garciduenas AL, Jimenez-Capdeville ME. Parkinson disease and progressive supranuclear palsy: protein expression in skin. Ann Clin Transl Neurol. 2016 Feb 1;3(3):191-9. doi: 10.1002/acn3.285. eCollection 2016 Mar.
- Background: PubMed 23635781Golde TE, Borchelt DR, Giasson BI, Lewis J. Thinking laterally about neurodegenerative proteinopathies. J Clin Invest. 2013 May;123(5):1847-55. doi: 10.1172/JCI66029. Epub 2013 May 1.
- Individual participant dataSharing planned: Undecided
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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.
Cristina Monzón Tapia, MD contact
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Alzheimer Disease and Frontotemporal Dementia, run by Universidad Autonoma de San Luis Potosí at 1 site in Mexico.
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 10 inclusion and 6 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 16 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 Mexico. 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 Ildefonso Rodríguez-Leyva, MD PhD (+52 444 834 2739, ilrole@yahoo.com.mx), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Aggregation pattern of a-synuclein, amyloid-b, p-TAU and TDP-43 (time frame: Each patient will be recruited and sampled the same day of the evaluation which will take about 1 hour. The final report it takes a frame time around two years.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06528964, which also lists 5 linked publications.
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 16 Dec 2024.