UMIN-CTR Clinical Trial

Public title

Japanese Alzheimer's Disease Neuroimaging Initiative, Second Stage

Acronym

J-ADNI2

Scientific Title

Japanese Alzheimer's Disease Neuroimaging Initiative, Second Stage

Scientific Title:Acronym

J-ADNI2

Region

Japan

Condition

mild cognitive impairment, preclinical Alzheimer disease

Classification by specialty

Neurology	Geriatrics	Psychiatry

Classification by malignancy

Others

Genomic information

YES

Narrative objectives1

To evaluate the progression of AD pathology at these very early stages, biomarkers (including neuroimaging) are mandatory. We have conducted Japanese AD Neuroimaging Initiative (J-ADNI) since 2007, achieving brain morphometry using MRI, functional imaging by PET, biomarker assessment in body fluids, studies on AD-related genes, and clinical/neuropsychological assessments in a longitudinal multisite clinical studies. We were able to predict conversion from MCI to AD dementia using amyloid signatures, and detect changes in neuroimaging prior to the onset of AD dementia, setting the bases for assessments in clinical trials for DMT. In the J-ADNI2 stage, we aim at focusing on early MCI and preclinical AD, in addition to late MCI we studied in J-ADNI1, describe the natural course of these prodromal stages of AD through observational studies, to diagnose individuals who have high risks for developing dementia.

Basic objectives2

Others

Basic objectives -Others

Towards the successful development of disease-modifying therapies (DMTs) for Alzheimer disease (AD), therapeutic intervention at the mild cognitive impairment (MCI) stage preceding AD dementia, and at the preclinical AD stage with AD pathology but without symptomatic manifestations, is required. J-ADNI2 study contributes to this goal.

Trial characteristics_1

Others

Trial characteristics_2

Others

Developmental phase

Not applicable

Primary outcomes

(1) preclinical AD study: progression rate to CDR 0.5 (MCI) stage in amyloid PET positive or negative groups
(2) MCI study: progression rate (conversion) to dementia in amyloid PET positive or negative groups

Key secondary outcomes

Rate of change in MRI brain morphometry, uptake in FDG-PET in amyloid PET positive or negative groups, cognitive tests, and their correlation with cerebrospinal fluid biomarkers and apoE genotype

Study type

Observational

Basic design

Randomization

Randomization unit

Blinding

Control

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

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

Age-lower limit

60

years-old

<=

Age-upper limit

84

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. In addition, participants in J-ADNI1 as cognitively normal, who had completed 3-year longitudinal study and were amyloid PET-positive or low CSF Abeta(1-42) (n=~20), will be asked about their willingness to further participate in J-ADNI2.
2. MCI study: 100 late MCI and 100 early MCI individuals who meet with the criteria of each type of MCI (below).In addition, participants in J-ADNI1 as (late) MCI, who had completed 3-year longitudinal study and were amyloid PET-positive or low CSF Abeta(1-42) (n=~20), will be asked about their willingness to further participate in J-ADNI2.
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: 65-84 years (preclinical AD study) and 60-84 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 J-ADNI2 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 J-ADNI.

Target sample size

500

Name of lead principal investigator

1st name
Middle name
Last name	Takeshi Iwatsubo

Organization

Graduate School of Medicine, The University of Tokyo

Division name

Department of Neuropathology and University Hospital

Zip code

Address

7-3-1 Hongo Bunkyoku Tokyo

TEL

03-5841-3541

Email

iwatsubo@m.u-tokyo.ac.jp

Name of contact person

1st name
Middle name
Last name	Takeshi Iwatsubo

Organization

Data Center of J-ADNI

Division name

Clinical Research Support Center, The University of Tokyo

Zip code

Address

7-3-1 Hongo Bunkyoku Tokyo

TEL

03-5841-3541

Homepage URL

Email

iwatsubo@m.u-tokyo.ac.jp

Institute

J-ADNI2 study group

Institute

Department

Personal name

Organization

NEDO, The Ministry of Health and Welfare

Organization

Division

Category of Funding Organization

Nationality of Funding Organization

Japan

Co-sponsor

Research Association for Biotechnology

Name of secondary funder(s)

Ministry of Economy, Trade and Industry; public funding from the pharmaceutical industry consortium at the Research Association for Biotechnology

Organization

Address

Tel

Email

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

東京大学医学部附属病院をはじめとする全国４１施設

Date of disclosure of the study information

2013

Year

06

Month

18

Day

URL releasing protocol

Publication of results

Unpublished

URL related to results and publications

Number of participants that the trial has enrolled

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

Terminated

Date of protocol fixation

2013

Year

05

Month

23

Day

Date of IRB

Anticipated trial start date

2013

Year

06

Month

24

Day

Last follow-up date

2018

Year

03

Month

31

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Clinical/neuropsychological evaluation, neuroimaging work-ups and collection of biofluid samples are undertaken longitudinally at baseline, 12,24,36 M (preclinical AD study), baseline, 6,12,24,36M (MCI study) . MRI (at every visit) and amyloid PET scan (at screening/baseline and 36M) will be performed in all cases.

Registered date

2013

Year

06

Month

18

Day

Last modified on

2015

Year

12

Month

18

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000012764