Alzheimer DiseaseNCT02129452
Olfactory Neuroepithelial Tissue of Alzheimer Disease
An observational study of Alzheimer Disease, run by Seoul National University Hospital at 1 site in South Korea.
Trial summary
The purpose of this study is to evaluate the olfactory neuroepithelium as a biomarker of Alzheimer disease. The early diagnosis of Alzheimer disease is of importance for obtaining better response to treatment, but recently reported biomarkers have some limitations. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Alzheimer Disease
- How many people
- 40 participants
- Where
- 1 siteSouth Korea
- Study dates
- Jan 2013to Feb 2015
- Phase
- Observational
- Are there results?
- None posted in the registry
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 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: primary care clinic
Who may be able to join
- "Probable" Alzheimer disease categorized according to NINCDS-ADRDA criteria
- Written or signed informed consent obtained voluntarily from the subject, or legally acceptable representative(s) in the case of "Vulnerable subjects" with CDR more than 1
Who cannot join
- Those who are not eligible for nasal cavity biopsy due to behavioral or movement disorder
- Those who are in a hypercoagulable state or who take anticoagulant drugs
- Those who have chronic or active allergic rhinitis which interfere accurate pathological evaluation
- Those who are not suitable for the study to the judgments of researchers
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Research of Olfactory Neuroepithelial Tissue as a Potential Biomarker of Alzheimer Disease
The purpose of this study is to evaluate the olfactory neuroepithelium as a biomarker of Alzheimer disease. The early diagnosis of Alzheimer disease is of importance for obtaining better response to treatment, but recently reported biomarkers have some limitations. Olfactory neuroepithelium tissue which is accessible through office-based biopsy without difficulty is known to reflect brain pathology that confirms the diagnosis of Alzheimer disease. This study will help in the early detection and treatment of Alzheimer disease.
Read the detailed description
Alzheimer disease is the most common form of dementia characterized by insidious onset and slow progression. Pathological changes in the brain of Alzheimer disease (AD) precede clinical symptoms many years, and early treatment provide better outcome. Consequently, detection of AD in early stages is needed. Biologic markers including beta-amyloid and tau protein have been studied for early diagnosis of AD. Recently remarkable biomarkers have drawn attention including CSF proteins and PIB (Amyloid-binding carbon 11-labeled Pittsburgh compound B) PET findings, but they pertain to supportive markers since they reflect brain pathology indirectly.
Postmortem studies of AD patients revealed that beta-amyloid and tau proteins are found in olfactory neuroepithelium and correlate with brain pathological changes. Olfactory neuroepithelium tissue can be obtained through office-based biopsy safely and easily by nasal endoscopy. Especially, early pathological changes of AD can be found in entorhinal cortex and piriform cortex adjacent to olfactory neuroepithelium, this study would be valuable for early detection of AD.
MicroRNAs are small, single-stranded RNA comprising about 20 nucleotides and involved in cell differentiation, growth and death. Recently the investigators reported that microRNA 206 have important role in pathomechanism of AD, thus can be new biomarker and disease-modifying therapeutic target of AD.
Study participants are enrolled from primary care clinic at department of Neurology, Seoul National University Hospital. Patients' clinical presentation, MMSE (Mini mental status exam), CDR (Clinical Dementia Rating) and ADAS-COG-K (Alzheimer Disease Assessment Scale Cognitive Subscale) are collected from routinely executed exams in the clinic. Participants are categorized into four groups according to CDR, and each group enrolls 10 patients respectively. The number of 10 patients per each group was calculated based on previous studies, costs, time and ethical perspectives.
Method for olfactory neuroepithelium biopsy was adopted from Lovell et al. (Arch Otolaryngol. 1982). Concentrations of beta-amyloid and tau proteins are analyzed from ELISA, and microRNA 206 from RT-PCR, northern blot and microarray. These data will be evaluated with clinical features and exam results of participants using general statistical methods.
- Conditions
- Alzheimer Disease
- Keywords
- Alzheimer disease, Dementia, Neurodegenerative Diseases, Tauopathies, Amyloid beta Peptides, Amyloid Plaque, MicroRNAs, Early Diagnosis
- Medical subject headings
- Alzheimer Disease, Dementia, Neurodegenerative Diseases, Tauopathies, Plaque, Amyloid, Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| CDR (Clinical dementia rating) 0 | 10 participants complaining subjective memory problem and acquiring CDR 0 | |
| CDR 0.5 | 10 participants complaining subjective memory problem and acquiring CDR 0.5 | |
| CDR 1 | 10 participants with mild cognitive impairment and acquiring CDR 1 | |
| CDR 2 | 10 participants with moderate to severe cognitive impairment and acquiring CDR 2 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pathological evidence of Alzheimer disease in the olfactory neuroepithelium
beta-amyloid protein, tau protein and micro-RNA 206 concentration according to disease progression
Measured: Baseline at the time of enrollment. Data will be evaluated in a month.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 May 2014 (estimated)
- Study startJan 2013
- Primary completionDec 2014
- Study completionFeb 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Alzheimer DiseaseStudies of the same condition, open and under way.
- More trials run by Seoul National 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
- Observational
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Seoul National University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Kon Chu, Seoul National University Hospital
- Investigators
- Kon Chu, MD, PhD, Principal investigator, Seoul National University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02129452
- Sponsor's protocol ID
- 1301056458
- Status last verified
- May 2015
- First submitted
- 28 Apr 2014
- Last updated
- 27 May 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
Lee ST, Chu K, Jung KH, Kim JH, Huh JY, Yoon H, Park DK, Lim JY, Kim JM, Jeon D, Ryu H, Lee SK, Kim M, Roh JK. miR-206 regulates brain-derived neurotrophic factor in Alzheimer disease model. Ann Neurol. 2012 Aug;72(2):269-77. doi: 10.1002/ana.23588.
PubMed 22926857Braak H, Braak E. Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol. 1991;82(4):239-59. doi: 10.1007/BF00308809.
PubMed 1759558Arnold SE, Lee EB, Moberg PJ, Stutzbach L, Kazi H, Han LY, Lee VM, Trojanowski JQ. Olfactory epithelium amyloid-beta and paired helical filament-tau pathology in Alzheimer disease. Ann Neurol. 2010 Apr;67(4):462-9. doi: 10.1002/ana.21910.
PubMed 20437581Dubois B, Feldman HH, Jacova C, Dekosky ST, Barberger-Gateau P, Cummings J, Delacourte A, Galasko D, Gauthier S, Jicha G, Meguro K, O'brien J, Pasquier F, Robert P, Rossor M, Salloway S, Stern Y, Visser PJ, Scheltens P. Research criteria for the diagnosis of Alzheimer's disease: revising the NINCDS-ADRDA criteria. Lancet Neurol. 2007 Aug;6(8):734-46. doi: 10.1016/S1474-4422(07)70178-3.
PubMed 17616482Attems J, Jellinger KA. Olfactory tau pathology in Alzheimer disease and mild cognitive impairment. Clin Neuropathol. 2006 Nov-Dec;25(6):265-71.
PubMed 17140156Lovell MA, Jafek BW, Moran DT, Rowley JC 3rd. Biopsy of human olfactory mucosa. An instrument and a technique. Arch Otolaryngol. 1982 Apr;108(4):247-9. doi: 10.1001/archotol.1982.00790520047013.
PubMed 7073597Wrobel BB, Mazza JM, Evgrafov OV, Knowles JA. Assessing the efficacy of endoscopic office olfactory biopsy sites to produce neural progenitor cell cultures for the study of neuropsychiatric disorders. Int Forum Allergy Rhinol. 2013 Feb;3(2):133-8. doi: 10.1002/alr.21080. Epub 2012 Nov 28.
PubMed 23192985
Study at a glance
From the registry record, last updated by the sponsor on 27 May 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Research of Olfactory Neuroepithelial Tissue as a Potential Biomarker of Alzheimer Disease
- ClinicalTrials.gov ID
- NCT02129452
- Acronym / sponsor ID
- 1301056458
- Conditions
- Alzheimer Disease
- Keywords
- Alzheimer disease, Dementia, Neurodegenerative Diseases, Tauopathies, Amyloid beta Peptides, Amyloid Plaque, MicroRNAs, Early Diagnosis
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Seoul National University HospitalUniversity, hospital or other
- Study start
- Jan 2013
- Primary completion
- Dec 2014 (actual)
- Study completion
- Feb 2015 (actual)
- First posted
- 2 May 2014 (estimated)
- 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 purpose of this study is to evaluate the olfactory neuroepithelium as a biomarker of Alzheimer disease. The early diagnosis of Alzheimer disease is of importance for obtaining better response to treatment, but recently reported biomarkers have some limitations. Olfactory neuroepithelium tissue which is accessible through office-based biopsy without difficulty is known to reflect brain pathology that confirms the diagnosis of Alzheimer disease. This study will help in the early detection and treatment of Alzheimer disease.
Detailed description
Alzheimer disease is the most common form of dementia characterized by insidious onset and slow progression. Pathological changes in the brain of Alzheimer disease (AD) precede clinical symptoms many years, and early treatment provide better outcome. Consequently, detection of AD in early stages is needed. Biologic markers including beta-amyloid and tau protein have been studied for early diagnosis of AD. Recently remarkable biomarkers have drawn attention including CSF proteins and PIB (Amyloid-binding carbon 11-labeled Pittsburgh compound B) PET findings, but they pertain to supportive markers since they reflect brain pathology indirectly.
Postmortem studies of AD patients revealed that beta-amyloid and tau proteins are found in olfactory neuroepithelium and correlate with brain pathological changes. Olfactory neuroepithelium tissue can be obtained through office-based biopsy safely and easily by nasal endoscopy. Especially, early pathological changes of AD can be found in entorhinal cortex and piriform cortex adjacent to olfactory neuroepithelium, this study would be valuable for early detection of AD.
MicroRNAs are small, single-stranded RNA comprising about 20 nucleotides and involved in cell differentiation, growth and death. Recently the investigators reported that microRNA 206 have important role in pathomechanism of AD, thus can be new biomarker and disease-modifying therapeutic target of AD.
Study participants are enrolled from primary care clinic at department of Neurology, Seoul National University Hospital. Patients' clinical presentation, MMSE (Mini mental status exam), CDR (Clinical Dementia Rating) and ADAS-COG-K (Alzheimer Disease Assessment Scale Cognitive Subscale) are collected from routinely executed exams in the clinic. Participants are categorized into four groups according to CDR, and each group enrolls 10 patients respectively. The number of 10 patients per each group was calculated based on previous studies, costs, time and ethical perspectives.
Method for olfactory neuroepithelium biopsy was adopted from Lovell et al. (Arch Otolaryngol. 1982). Concentrations of beta-amyloid and tau proteins are analyzed from ELISA, and microRNA 206 from RT-PCR, northern blot and microarray. These data will be evaluated with clinical features and exam results of participants using general statistical methods.
Study design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| CDR (Clinical dementia rating) 0 | – | –10 participants complaining subjective memory problem and acquiring CDR 0 |
| CDR 0.5 | – | –10 participants complaining subjective memory problem and acquiring CDR 0.5 |
| CDR 1 | – | –10 participants with mild cognitive impairment and acquiring CDR 1 |
| CDR 2 | – | –10 participants with moderate to severe cognitive impairment and acquiring CDR 2 |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- primary care clinic
Key inclusion criteria (2 listed)
- "Probable" Alzheimer disease categorized according to NINCDS-ADRDA criteria
- Written or signed informed consent obtained voluntarily from the subject, or legally acceptable representative(s) in the case of "Vulnerable subjects" with CDR more than 1
Key exclusion criteria (4 listed)
- Those who are not eligible for nasal cavity biopsy due to behavioral or movement disorder
- Those who are in a hypercoagulable state or who take anticoagulant drugs
- Those who have chronic or active allergic rhinitis which interfere accurate pathological evaluation
- Those who are not suitable for the study to the judgments of researchers
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Pathological evidence of Alzheimer disease in the olfactory neuroepithelium
Time frame: Baseline at the time of enrollment. Data will be evaluated in a month.
beta-amyloid protein, tau protein and micro-RNA 206 concentration according to disease progression
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 May 2015.
- Background: PubMed 22926857Lee ST, Chu K, Jung KH, Kim JH, Huh JY, Yoon H, Park DK, Lim JY, Kim JM, Jeon D, Ryu H, Lee SK, Kim M, Roh JK. miR-206 regulates brain-derived neurotrophic factor in Alzheimer disease model. Ann Neurol. 2012 Aug;72(2):269-77. doi: 10.1002/ana.23588.
- Background: PubMed 1759558Braak H, Braak E. Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol. 1991;82(4):239-59. doi: 10.1007/BF00308809.
- Background: PubMed 20437581Arnold SE, Lee EB, Moberg PJ, Stutzbach L, Kazi H, Han LY, Lee VM, Trojanowski JQ. Olfactory epithelium amyloid-beta and paired helical filament-tau pathology in Alzheimer disease. Ann Neurol. 2010 Apr;67(4):462-9. doi: 10.1002/ana.21910.
- Background: PubMed 17616482Dubois B, Feldman HH, Jacova C, Dekosky ST, Barberger-Gateau P, Cummings J, Delacourte A, Galasko D, Gauthier S, Jicha G, Meguro K, O'brien J, Pasquier F, Robert P, Rossor M, Salloway S, Stern Y, Visser PJ, Scheltens P. Research criteria for the diagnosis of Alzheimer's disease: revising the NINCDS-ADRDA criteria. Lancet Neurol. 2007 Aug;6(8):734-46. doi: 10.1016/S1474-4422(07)70178-3.
- Background: PubMed 17140156Attems J, Jellinger KA. Olfactory tau pathology in Alzheimer disease and mild cognitive impairment. Clin Neuropathol. 2006 Nov-Dec;25(6):265-71.
- Background: PubMed 7073597Lovell MA, Jafek BW, Moran DT, Rowley JC 3rd. Biopsy of human olfactory mucosa. An instrument and a technique. Arch Otolaryngol. 1982 Apr;108(4):247-9. doi: 10.1001/archotol.1982.00790520047013.
- Background: PubMed 23192985Wrobel BB, Mazza JM, Evgrafov OV, Knowles JA. Assessing the efficacy of endoscopic office olfactory biopsy sites to produce neural progenitor cell cultures for the study of neuropsychiatric disorders. Int Forum Allergy Rhinol. 2013 Feb;3(2):133-8. doi: 10.1002/alr.21080. Epub 2012 Nov 28.
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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. This study is not recruiting at the moment.
Kon Chu, MD, PhD principal investigator
Seoul National University Hospital
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, run by Seoul National University Hospital at 1 site in South Korea.
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 2 inclusion and 4 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: finished, as of the sponsor's last update on 27 May 2015. 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 South Korea. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pathological evidence of Alzheimer disease in the olfactory neuroepithelium (time frame: Baseline at the time of enrollment. Data will be evaluated in a month.). 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 NCT02129452, which also lists 7 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 27 May 2015.