UMIN-CTR Clinical Trial

Public title

Development of CSF/plasma biomarker which can predict onset of Alzheimer's disease

Acronym

Development of Alzheimer's disease biomarker

Scientific Title

Development of CSF/plasma biomarker which can predict onset of Alzheimer's disease

Scientific Title:Acronym

Development of Alzheimer's disease biomarker

Region

Japan

Condition

Alzheimer's disease

Classification by specialty

Psychiatry

Classification by malignancy

Others

Genomic information

NO

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

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

Study type

Interventional

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

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

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

Name of lead principal investigator

1st name
Middle name
Last name	Masayasu Okochi

Organization

Osaka University Graduate School of Medicine

Division name

Department of Neuropsychiatry

Zip code

Address

D3 2-2 Yamadaoka Suita, Osaka Japan

TEL

06-6879-3051

Email

mokochi@psy.med.osaka-u.ac.jp

Name of contact person

1st name
Middle name
Last name	Masayasu Okochi

Organization

Osaka University Graduate School of Medicine

Division name

Department of Neuropsychiatry

Zip code

Address

D3 2-2 Yamadaoka Suita, Osaka Japan

TEL

06-6879-3051

Homepage URL

Email

mokochi@psy.med.osaka-u.ac.jp

Institute

Osaka University

Institute

Department

Personal name

Organization

Japanese Education Ministry

Organization

Division

Category of Funding Organization

Japanese Governmental office

Nationality of Funding Organization

Japan

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)

Organization

Address

Tel

Email

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

大阪大学医学部附属病院　神経科精神科

Date of disclosure of the study information

2016

Year

12

Month

12

Day

URL releasing protocol

Publication of results

Partially published

URL related to results and publications

https://www.ncbi.nlm.nih.gov/pubmed/20049724

Number of participants that the trial has enrolled

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.

Results date posted

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Participant flow

Adverse events

Outcome measures

Plan to share IPD

IPD sharing Plan description

Recruitment status

Open public recruiting

Date of protocol fixation

2008

Year

02

Month

08

Day

Date of IRB

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

Other related information

Registered date

2016

Year

11

Month

27

Day

Last modified on

2016

Year

11

Month

27

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000028773