UMIN-CTR Clinical Trial

Basic information
Official scientific title of the study	Development of CSF/plasma biomarker which can predict onset of Alzheimer's disease
Title of the study (Brief title)	Development of Alzheimer's disease biomarker
Region	Japan

Condition
Condition	Alzheimer's disease
Classification by specialty	Psychiatry
Classification by malignancy	Others
Genomic information	NO

Objectives
Narrative objectives1	In AD brain, Abeta42 peptide is accumulated. Due to the accumulation, its value in CSF is rather lowered in the patients. We discovered some Abeta like peptides which are produced by BACE and gamma-secretase just like Abeta. By measuring the levels of these peptides in CSF/plasma, we can estimate Abeta production or degradation in brain.
Basic objectives2	Others
Basic objectives -Others	Development of AD onset prediction marker
Trial characteristics_1	Exploratory
Trial characteristics_2
Developmental phase

Assessment
Primary outcomes	We investigate how the value or the ratio of Abeta like peptides change in CSF or plasma of AD, MCI, or preclinical AD patients.
Key secondary outcomes

Base
Study type	Interventional

Study design
Basic design	Parallel
Randomization	Non-randomized
Randomization unit
Blinding	Open -but assessor(s) are blinded
Control	No treatment
Stratification
Dynamic allocation
Institution consideration
Blocking
Concealment

Intervention
No. of arms	2
Purpose of intervention	Diagnosis
Type of intervention	Other
Interventions/Control_1	AD or MCI patients in neuropsychiatry department in Osaka University are recruited. They undergo cognition tests including MMSE and CSF and/or blood sampling.
Interventions/Control_2	Non-AD patients in neuropsychiatry department in Osaka University are recruited. They undergo cognition tests including MMSE and CSF and/or blood sampling.
Interventions/Control_3
Interventions/Control_4
Interventions/Control_5
Interventions/Control_6
Interventions/Control_7
Interventions/Control_8
Interventions/Control_9
Interventions/Control_10

Eligibility
Age-lower limit	30 years-old <=
Age-upper limit	90 years-old >=
Gender	Male and Female
Key inclusion criteria	Patients who are clinically diagnosed as Alzheimer`s Disease, MCI, or non-AD.
Key exclusion criteria	not particular
Target sample size	1000

Research contact person
Name of lead principal investigator	Masayasu Okochi
Organization	Osaka University Graduate School of Medicine
Division name	Department of Neuropsychiatry
Address	D3 2-2 Yamadaoka Suita, Osaka Japan
TEL	06-6879-3051
Email	mokochi@psy.med.osaka-u.ac.jp

Public contact
Name of contact person	Masayasu Okochi
Organization	Osaka University Graduate School of Medicine
Division name	Department of Neuropsychiatry
Address	D3 2-2 Yamadaoka Suita, Osaka Japan
TEL	06-6879-3051
Homepage URL
Email	mokochi@psy.med.osaka-u.ac.jp

Sponsor
Institute	Osaka University
Institute
Department

Funding Source
Organization	Japanese Education Ministry
Organization
Division
Category of Funding Organization	Japanese Governmental office
Nationality of Funding Organization	Japan

Other related organizations
Co-sponsor	J-ADNI Osaka University Mental Health Promotion Higashi Matsudo Hospital Dept. of Mol. Genetics, Brain Res. Institute, Niigata Univ
Name of secondary funｄer(s)

Secondary IDs
Secondary IDs	YES
Study ID_1	07176-6
Org. issuing International ID_1	Osaka University Hospital
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions
Institutions	大阪大学医学部附属病院　神経科精神科

Other administrative information
Date of disclosure of the study information	2016 Year 12 Month 12 Day

Progress
Recruitment status	Open public recruiting
Date of protocol fixation	2008 Year 02 Month 08 Day
Anticipated trial start date	2008 Year 02 Month 08 Day
Last follow-up date
Date of closure to data entry
Date trial data considered complete
Date analysis concluded

Related information
URL releasing protocol
Publication of results	Partially published
URL releasing results	https://www.ncbi.nlm.nih.gov/pubmed/20049724
Results	Surrogate markers for the Alzheimer disease (AD)-associated 42-amino acid form of amyloid-beta (Abeta42) have been sought because they may aid in the diagnosis of AD and for clarification of disease pathogenesis. Here, we demonstrate that human cerebrospinal fluid (CSF) contains three APLP1-derived Abeta-like peptides (APL1beta) that are generated by beta- and gamma-cleavages at a concentration of approximately 4.5 nM. These novel peptides, APL1beta25, APL1beta27 and APL1beta28, were not deposited in AD brains. Interestingly, most gamma-secretase modulators (GSMs) and familial AD-associated presenilin1 mutants that up-regulate the relative production of Abeta42 cause a parallel increase in the production of APL1beta28 in cultured cells. Moreover, in CSF from patients with pathological mutations in presenilin1 gene, the relative APL1beta28 levels are higher than in non-AD controls, while the relative Abeta42 levels are unchanged or lower. Most strikingly, the relative APL1beta28 levels are higher in CSF from sporadic AD patients (regardless of whether they are at mild cognitive impairment or AD stage), than those of non-AD controls. Based on these results, we propose the relative level of APL1beta28 in the CSF as a candidate surrogate marker for the relative level of Abeta42 production in the brain.
Other related information

Management information
Registered date	2016 Year 11 Month 27 Day
Last modified on	2016 Year 11 Month 27 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000028773