UMIN-CTR Clinical Trial

Basic information
Official scientific title of the study	Analysis of Alzheimer disease mechanism using iPS derived human cortical neuron
Title of the study (Brief title)	Analysis of Alzheimer disease mechanism using iPS derived human cortical neuron
Region	Japan

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

Objectives
Narrative objectives1	By using iPS-derived cortical neurons of AD and non AD control, we aim to analyze Abeta production mechanism and effects of disease course modifiers.
Basic objectives2	Pharmacokinetics
Basic objectives -Others
Trial characteristics_1	Exploratory
Trial characteristics_2	Explanatory
Developmental phase

Assessment
Primary outcomes	We aim to analyze Abeta production mechanism and effects of disease course modifiers.
Key secondary outcomes

Base
Study type	Observational

Study design
Basic design
Randomization
Randomization unit
Blinding
Control
Stratification
Dynamic allocation
Institution consideration
Blocking
Concealment

Intervention
No. of arms
Purpose of intervention
Type of intervention
Interventions/Control_1
Interventions/Control_2
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	60 years-old <=
Age-upper limit	80 years-old >
Gender	Male and Female
Key inclusion criteria	Alzheimer's disease patients and non-AD patients
Key exclusion criteria	other dementia than AD
Target sample size	8

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	+81-6879-3051
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	+81-6879-3051
Homepage URL
Email	mokochi@psy.med.osaka-u.ac.jp

Sponsor
Institute	Osaka University
Institute
Department

Funding Source
Organization	Others
Organization
Division
Category of Funding Organization	Profit organization
Nationality of Funding Organization	Japan

Other related organizations
Co-sponsor	Shionogi pharmaceutical company
Name of secondary funｄer(s)

Secondary IDs
Secondary IDs	NO
Study ID_1
Org. issuing International ID_1
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions
Institutions	大阪大学大学院医学系研究科

Other administrative information
Date of disclosure of the study information	2016 Year 11 Month 21 Day

Progress
Recruitment status	Completed
Date of protocol fixation	2015 Year 02 Month 02 Day
Anticipated trial start date	2015 Year 02 Month 02 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	Published
URL releasing results	https://www.ncbi.nlm.nih.gov/pubmed/28978478
Results	gamma-secretase inhibitors (GSI) are drugs developed to decrease amyloid-beta peptide (Abeta) production by inhibiting intramembranous cleavage of beta-amyloid protein precursor (betaAPP). However, a large phase 3 trial of semagacestat, a potential non-transition state analog (non-TSA) GSI, in patients with Alzheimer's disease (AD) was terminated due to unexpected aggravation of cognitive deficits and side effects. Here, we show that some semagacestat effects are clearly different from a phenotype caused by a loss of function of presenilins, core proteins in the gamma-secretase complex. Semagacestat increases intracellular byproduct peptides, produced along with Abeta through serial gamma-cleavage of betaAPP, as well as intracellular long Abeta species, in cell-based and in vivo studies of AD model mice. Other potential non-TSA GSIs, but not L685,458, a TSA GSI, have similar effects. Furthermore, semagacestat inhibits release of de novo intramembranous gamma-byproducts to the soluble space. Thus, semagacestat is a pseudo-GSI, and therefore, the semagacestat clinical trial did not truly test the Abeta hypothesis.
Other related information	The results are described in the Results. Other studies using iPS derived neurons are on going.

Management information
Registered date	2016 Year 11 Month 19 Day
Last modified on	2017 Year 12 Month 20 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000028660