UMIN-CTR Clinical Trial

Public title

Clinical and neuroimaging study on preclinical Alzheimer's disease.

Acronym

AMED-Preclinical

Scientific Title

Clinical and neuroimaging study on preclinical Alzheimer's disease.

Scientific Title:Acronym

AMED-Preclinical

Region

Japan

Condition

mild cognitive impairment, preclinical Alzheimer disease

Classification by specialty

Neurology	Geriatrics	Psychiatry

Classification by malignancy

Others

Genomic information

YES

Narrative objectives1

This clinical study aims to discriminate MCI individuals at risk for development of Alzheimer dementia, as well as preclinical AD without clinical manifestations.

Basic objectives2

Others

Basic objectives -Others

It is necessary to start treatment at the earliest stage of Alzheimer disease to successfully develop drugs (disease-modifying therapies: DMTs). This study aims to establish the criteria for evaluation of the earliest stage of Alzheimer disease and to analyze the genes that related Alzheimer disease.

Trial characteristics_1

Others

Trial characteristics_2

Others

Developmental phase

Not applicable

Primary outcomes

Cognitive assessments, brain imaging, and biomarkers in cerebrospinal fluid, and estimation of conversion rate from asymptomatic preclinical AD to MCI and further to AD dementia.

Key secondary outcomes

The evaluation of correlation among indexes such as amyloid-PET, neuropsychometry, brain imaging, and biomarkers in cerebrospinal fluid. Genetic analysis of APP, presenilin (PSEN 1,PSEN 2) and related genes (MAPT,PGRNetc.), and comparison between the phenotype (symptoms) and the genotype of whole genome.

Study type

Interventional

Basic design

Single arm

Randomization

Non-randomized

Randomization unit

Blinding

Open -no one is blinded

Control

Self control

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

No. of arms

1

Purpose of intervention

Prevention

Type of intervention

Medicine

Interventions/Control_1

Neuroimaging study using PET diagnostics not yet approved for diagnostic indications (brain PET scan using 11C-PiB, florbetapir or flutemetamol at 0 and 36 months)

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

Age-lower limit

60

years-old

<=

Age-upper limit

85

years-old

>=

Gender

Male and Female

Key inclusion criteria

1. Preclinical AD study: 150 amyloid PET-positive and 150 amyloid PET-negative cognitively normal individuals, whose language is Japanese.
2. MCI study: 100 late MCI and 100 early MCI individuals who meet with the criteria of each type of MCI (below).
3. Living at home, accompanied by a study partner who has a direct contact with the participant >10 hr per week. The participant should be accompanied by the study partner at every visit throughout the study.
4.The participants and study partners should sign agreement forms.
5. Age: 65-85 years (preclinical AD study) and 60-85 years (MCI study) upon enrollment. Individuals of both sexes will be enrolled.
6a. Criteria for participants in preclinical AD study
MMSE: 24-30
Scores of Wechsler memory Scale-R logical memory II (corrected for education), above the cut-off levels.
education 0-7 years: 3 or above
8-15 years: 5 or above
>16 years 9 or above
CDR 0, not depressed
Individuals who are amyloid PET-positive upon screen scan are categorized as "preclinical AD" and amyloid PET-negative as "normal aged".
6b. Criteria for amnestic MCI
Memory disturbance approved by the participant or study partner or clinician.
MMSE: 24-30
Scores of Wechsler memory Scale-R logical memory II (corrected for education), below the cut-off levels.
education 0-7 years: 2 or lower (late MCI); 3-6 (early MCI)
10-15 years: 4 or lower (late MCI); 5-9 (early MCI)
>16 years 8 or lower (late MCI); 9-11 (early MCI)
CDR 0.5 not depressed

Key exclusion criteria

1. Parkinson' disease, Lewy body dementia, frontotemporal dementia, Huntington's disease, progressive supranuclear palsy or other neurodegenerative diseases other than AD. Multiple cerebral infarction, normal pressure hydrocephalus, brain tumor, epilepsy, subdural hematoma, multiple sclerosis, head trauma with sequelae will also be excluded.
2. Signs of brain infection, focal brain lesions (eg infarction) that may affect cognitive function. Individuals with subcortical small infarction or diffuse white matter lesions can be included except for those in specific lesions affecting cognition. Cortical infarcts are normally excluded.
3. Presence of pacemaker, arterial clip, artificial valves, artificial cochlea, and other magnetic/electroconductive metals in the body that may affect MRI scan.
4. Major depression or bipolar disorder within past 1 year, past history of schizophrenia, defined by DSM-IV.
5. Addiction to alcohol or other drugs within past 2 years.
6. Past history of psychiatric symptoms, agitation or abnormal behaviors that affect protocol adherence within past 3 months.
7. Presence of fatal or unstable diseases.
8. Vitamin B12 or folate deficiency, syphilis, thyroid function abnormality.
9. Admission to care home or hospitals.
10. Administration of specific drugs (defined in the procedure manual) including psychoactive drugs and warfarin.
11. Administration of any drugs in clinical trial within 1 month prior to screening.
12. Participation in clinical studies or clinical trials other than AMED preclinical.
13. Probable participation in clinical trials for Alzheimer's disease drugs during the study duration of 3 years.
14. Decision of exclusion otherwise judged by site study physician or clinical core.

Target sample size

500

Name of lead principal investigator

1st name	Hiroyuki
Middle name
Last name	Shimada

Organization

Graduate School of medicine, Osaka City University

Division name

Department of Diagnostic and Interventional Radiology

Zip code

545-8585

Address

1-4-3 Asahimachi, Abenoku, Osaka

TEL

06-6646-6185

Email

h.shimada@med.osaka-cu.ac.jp

Name of contact person

1st name	Hiroyuki
Middle name
Last name	Shimada

Organization

Graduate School of medicine, Osaka City Nuversity

Division name

Center for Clinical study on dementia

Zip code

545-8585

Address

1-4-3 Asahimachi, Abenoku, Osaka

TEL

06-6646-6185

Homepage URL

Email

h.shimada@med.osaka-cu.ac.jp

Institute

Osaka City University

Institute

Department

Personal name

Organization

AMED

Organization

Division

Category of Funding Organization

Government offices of other countries

Nationality of Funding Organization

Japan

Co-sponsor

Osaka city university hospital and 35 hospitals in Japan

Name of secondary funder(s)

Organization

Osaka City University Hospital Certified Review Board

Address

AbenoMedix 6F, 1-2-7, Asahi-machi Abeno-ku, Osaka, 545 -8585, Japan Osaka

Tel

06-6645-3456

Email

irb@med.osaka-cu.ac.jp

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

大阪市立大学医学部附属病院と全国35医療研究機関
Osaka city university hospital and other 35 hospitals in Japan

Date of disclosure of the study information

2015

Year

12

Month

01

Day

URL releasing protocol

Publication of results

Unpublished

URL related to results and publications

Number of participants that the trial has enrolled

40

Results

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

No longer recruiting

Date of protocol fixation

2015

Year

09

Month

01

Day

Date of IRB

2015

Year

09

Month

01

Day

Anticipated trial start date

2016

Year

11

Month

01

Day

Last follow-up date

2020

Year

03

Month

31

Day

Date of closure to data entry

2020

Year

03

Month

31

Day

Date trial data considered complete

2020

Year

06

Month

30

Day

Date analysis concluded

2021

Year

03

Month

31

Day

Other related information

AMED Preclinical AD study Manuscript Citations (Sep 2020)

By-line:

Include the phrase "AMED Preclinical AD study *" with the asterisk referring to the following statement and list of names:

*Data used in preparation of this article were obtained from the AMED Preclinical AD study database deposited in the National Bioscience Database Center Human Database, Japan (Research ID: hum0235.v1, 2020). As such, the investigators within AMED Preclinical AD study contributed to the design and implementation of AMED Preclinical AD study and/or provided data but did not participate in analysis or writing of this report.

A complete listing of AMED Preclinical AD study investigators can be found at:
https://humandbs.biosciencedbc.jp/en/hum0235-clinical-sites
https://humandbs.biosciencedbc.jp/hum0235-clinical-sites


Methods Section:

Data used in preparation of this article were obtained from the AMED Preclinical AD study database deposited in the National Bioscience Database Center Human Database, Japan (Research ID: hum0235.v1, 2020). The AMED Preclinical AD study was launched in 2015 led by Principal Investigator Hiroshi Mori, PhD. The primary goal of AMED Preclinical AD study has been to test whether serial magnetic resonance imaging (MRI), positron emission tomography (PET), other biological markers, and clinical and neuropsychological assessment can be combined to measure the progression of early and late mild cognitive impairment (MCI) and Preclinical Alzheimer's disease (AD) in the Japanese population.

Acknowledgements Section:

AMED Preclinical AD study was supported by the grant of the Japan Agency for Medical Research and Developmential.

Registered date

2015

Year

11

Month

25

Day

Last modified on

2022

Year

06

Month

10

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000022596