UMIN-CTR Clinical Trial

Public title

Safety and efficacy of rosmarinic acid in patients with Alzheimer's disease: Double blind placebo-controlled study

Acronym

Safety and efficacy of rosmarinic acid in patients with Alzheimer's disease: Double blind placebo-controlled study

Scientific Title

Safety and efficacy of rosmarinic acid in patients with Alzheimer's disease: Double blind placebo-controlled study

Scientific Title:Acronym

Safety and efficacy of rosmarinic acid in patients with Alzheimer's disease: Double blind placebo-controlled study

Region

Japan

Condition

Alzheimer's disease

Classification by specialty

Neurology

Classification by malignancy

Others

Genomic information

YES

Narrative objectives1

The purpose of the study is to evaluate safety and tolerability of long-term intake of rosmarinic acid in patients with Alzheimer's disease.

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Exploratory

Trial characteristics_2

Explanatory

Developmental phase

Phase I,II

Primary outcomes

To evaluate safety and tolerability of long-term intake of rosmarinic acid.
Including incidence of adverse event, physical examination, neurological examination, vital signs, laboratory examination and cognitive tests. The ratio of the patients who completed the course of rosmarinic acid intake (200mg-500mg per day) for 48 weeks.

Key secondary outcomes

To evaluate the changes of cognitive tests between screening and post-intake of rosmarinic acid.
1: Significant improvement, 2: Improvement, 3: No change, 4: Slight deterioration, 5: Deterioration, 6: Can not be determined.
To evaluate the changes of PIB-PET, FDG-PET, cerebrospinal fluid biomarkers (Abeta1-42, total tau protein, phosphorylated tau protein) between screening and 24th week of the study.

Study type

Interventional

Basic design

Parallel

Randomization

Randomized

Randomization unit

Individual

Blinding

Double blind -all involved are blinded

Control

Placebo

Stratification

YES

Dynamic allocation

NO

Institution consideration

Institution is not considered as adjustment factor.

Blocking

NO

Concealment

No need to know

No. of arms

2

Purpose of intervention

Treatment

Type of intervention

Food

Interventions/Control_1

Actural drug group
1)To take 200mg (4capsules) rosmarinic acid per day for 2 weeks after the start of the test.
2)To take 400mg (8capsules) rosmarinic acid per day for 2nd-4th weeks.
3)To take 500mg (10capsules) rosmarinic acid per day for 4th-48th weeks.
4)To stop rosmarinic acid administration at 48th week of the test.

Interventions/Control_2

Placebo group
1)To take placebo (4capsules) per day for 2 weeks after the start of the test.
2)To take placebo (8capsules) per day for 2nd-4th weeks.
3)To take placebo (10capsules) per day for 4th-24th weeks.
4)To stop placebo administration and start rosmarinic acid intake at 24th week of the test.
5)To take 200mg (4capsules) rosmarinic acid and placebo (6capsules) per day for 24th-26th weeks.
6)To take 400mg (8capsules) rosmarinic acid and placebo (2capsules) per day for 26th-28th weeks.
7)To take 500mg (10capsules) rosmarinic acid per day for 28th-48th weeks.
8)To stop rosmarinic acid administration at 48th week of the test.

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

Not applicable

Gender

Male and Female

Key inclusion criteria

1.Alzheimer's disease outpatients older than 60 years old at informed consent.
2.Patients with probable AD dementia with evidence of the AD pathophysiological process (Biomarker probability of AD etiology High) according to the criteria of National Institute on Aging-Alzheimer's Association workgroups (NIA-AA).
3.MMSE score 20-26 points and CDR score 0.5 or 1.
4.Patient could be distinguished from other dementia disorders.
5.Patient can administrate the tablets and patient and patient's family can manage taking medicine.
6.Written informed consent of patient and patient's family.

Key exclusion criteria

1.Patients taken supplements which contain polyphenols within 1 month.
2.Patients with severe heart disease, liver disease, kidney disease.
3.Patients who has malignancy.
4.Patients who has previous history of alchol and/or drug abuse.
5.Patients who has hypersensitivity to polyphenols.
6.Patients who has drug and/or food allergy.
7.Patients participating in other clinical trials.
8.Patients newly administrated other dementia therapeutics within 60 days including Galantamine Hydromide (Reminyl, Takeda pharmaceutical company limited. Janssen pharmaceutica), Memantine Hydrochoride (Memary, DaiichiSankyo company limited), Rivastigmine (Exelon patch, Novartis/ Rivastach patch, Ono pharmaceutical company limited), Donepezil Hydrochloride (Aricept, Aricept D, Eisai). During this trial, addition and change of other dementia therapeutic drugs are not permitted in principle.
9.The patients judged to inadequacy by the attending physician or principal investigator.

Target sample size

20

Name of lead principal investigator

1st name
Middle name
Last name	Masahito Yamada

Organization

Kanazawa University Graduate School of Medical Science

Division name

Department of Neurology and Neurobiology of Aging

Zip code

Address

13-1 Takara-machi, Kanazawa, Ishikawa, 920-8641, Japan

TEL

076-265-2000

Email

m-yamada@med.kanazawa-u.ac.jp

Name of contact person

1st name
Middle name
Last name	Kenjiro Ono, Moeko Shinohara

Organization

Kanazawa University Graduate School of Medical Science

Division name

Department of Neurology and Neurobiology of Aging

Zip code

Address

13-1 Takara-machi, Kanazawa, Ishikawa, 920-8641, Japan

TEL

076-265-2292

Homepage URL

http://web.kanazawa-u.ac.jp/~med19/

Email

onoken@med.kanazawa-u.ac.jp

Institute

Kanazawa University Graduate School of Medical Science

Institute

Department

Personal name

Organization

Japan Society for the Promotion of Science

Organization

Division

Category of Funding Organization

Other

Nationality of Funding Organization

Japan

Co-sponsor

Takasaki University of Health and welfare
Tokyo University Graduate School of Agricaltural and Life Sciences

Name of secondary funder(s)

Maruzen Pharmacenticals company limited

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

金沢大学病院（石川県）
kanazawa University Hospital (Ishikawa)

Date of disclosure of the study information

2012

Year

04

Month

16

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

Completed

Date of protocol fixation

2012

Year

02

Month

15

Day

Date of IRB

Anticipated trial start date

2012

Year

04

Month

01

Day

Last follow-up date

2016

Year

09

Month

30

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2012

Year

04

Month

12

Day

Last modified on

2016

Year

10

Month

21

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000009110