UMIN-CTR Clinical Trial

Basic information
Public title	Community-based study about the efficacy of Melissa officinalis extract which contained rosmarinic acid on cognitive function in older adults with subjective cognitive impairment and mild cognitive impairment: A double blind, placebo-controlled, parallel-design, randomized control trial
Acronym	Noto Rosmarinic Acid Project for Prevention of Dementia
Scientific Title	Community-based study about the efficacy of Melissa officinalis extract which contained rosmarinic acid on cognitive function in older adults with subjective cognitive impairment and mild cognitive impairment: A double blind, placebo-controlled, parallel-design, randomized control trial
Scientific Title:Acronym	Noto Rosmarinic Acid Project for Prevention of Dementia
Region	Japan

Condition
Condition	subjective cognitive impairment and mild cognitive impairment
Classification by specialty	Neurology Adult
Classification by malignancy	Others
Genomic information	YES

Objectives
Narrative objectives1	Evaluate the efficacy of Melissa officinalis extract which contained rosmarinic acid in older adults with subjective cognitive impairment and mild cognitive impairment
Basic objectives2	Efficacy
Basic objectives -Others
Trial characteristics_1	Confirmatory
Trial characteristics_2
Developmental phase	Phase II,III

Assessment
Primary outcomes	The changes of ADAS-cog scores between baseline and 48-week/ 96-week after intake of rosmarinic acid
Key secondary outcomes	(1) Comprehensive effects: The changes of CDR-SB scores between baseline and 48-week/ 96-week after intake of rosmarinic acid (2) Efficacy of prevention on the developing dementia: The incidence of dementia defined as Major neurocognitive disorder in DSM-5 (3) The total volume of the hippocampus: The changes of the total hippocampal volume quantified by MRI between baseline and 96-week after intake of rosmarinic acid (4) Activities of daily living: The changes of Barthel index and IADL scores between baseline and 48-week/ 96-week after intake of rosmarinic acid (5) Neuropsychological evaluation: The changes of MMSE scores between baseline and 48-week/ 96-week after intake of rosmarinic acid (6) Safety of rosmarinic acid: To evaluate safety of long-term intake of rosmarinic acid. Including incidence of adverse event, vital signs, laboratory examination, and head MRI. (7) The changes of biomarkers (blood amyloid-beta protein etc) and the association between biomarkers and cognition (ADAS-cog score etc) (8) Compliance rate: The differences of the results of Primary and Secondary outcomes for each compliance rate

Base
Study type	Interventional

Study design
Basic design	Parallel
Randomization	Randomized
Randomization unit	Individual
Blinding	Double blind -all involved are blinded
Control	Placebo
Stratification	YES
Dynamic allocation	YES
Institution consideration	Institution is not considered as adjustment factor.
Blocking	NO
Concealment	Central registration

Intervention
No. of arms	2
Purpose of intervention	Prevention
Type of intervention	Food
Interventions/Control_1	(1) To take 500 mg (10 capsules) rosmarinic acid per day for 96weeks (2) To stop rosmarinic acid administration at 96th week of the test
Interventions/Control_2	(1) To take placebo (10 capsules) per day for 96 weeks (2) To stop placebo administration at 96th 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

Eligibility
Age-lower limit	65 years-old <=
Age-upper limit	79 years-old >=
Gender	Male and Female
Key inclusion criteria	1. Age between 65-79 years old at informed consent 2. Residents in Nanao-city, Japan and its environs 3. Subjects fulfilled the diagnostic criteria of subjective cognitive impairment and mild cognitive impairment 4. MMSE score more than 24 points at screening test 5. Subjects have reading comprehension equivalent to the six grade of elementary school, and subjects without intellectual disabilities 6. Physical findings, vital signs, and laboratory examination at screening test are within normal limits or within the acceptable range 7. Subjects agree to provide a blood or urine to test laboratory examination and APOE genotype 8. Subjects can administrate the tablets and subject's family can manage taking medicine 9. Subjects agree not to change the lifestyle such as exercise and eating habits
Key exclusion criteria	1. Subjects who have mental illness such as schizophrenia, bipolar disorder, depression etc. based on the diagnostic criteria of DSM-5 2. GDS-15 score more than 6 points at screening test 3. Subjects with uncontrolled health problem such as diabetes mellitus, hypertension, heart failure, angina pectoris, renal dysfunction, etc.. within 3 months before screening period. The researcher determines that there is a medically significant risk 4. Subjects who has malignancy within 5 years before screening period. Except for the low risk of recurrence cases who has no recurrence for 3 years. The researcher must determine whether to exclude the subjects with malignancy 5. Subjects administrated the prohibited concomitant therapy within prohibition period shown in Table1 6. Subjects who has previous history of alcohol and/or drug abuse 7. Subjects who has hypersensitivity to polyphenols 8. Subjects who has drug and/or food allergy 9. The subjects judged to inadequacy by the researcher Table1. Prohibited concomitant therapy (Prohibition period) Cholinesterase inhibitors and glutamate NMDA receptor antagonist (3 months) Daily administration of anticholinergic drugs (4 weeks) Antidepressant drugs (4 weeks) Antipsychotic drugs (4 weeks) Mood-stabilizing drugs and anticonvulsants (4 weeks) Daily administration of hypnotic, sedative/benzodiazepines (4 weeks) Daily administration of narcotic analgesics (4 weeks) Anti-Parkinson's disease treatment drugs (3 months)
Target sample size	330

Research contact person
Last 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	076-254-2290
Email	m-yamada@med.kanazawa-u.ac.jp

Public contact
1st name of contact person	1st name Middle name Last name 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
Email	m-nohara@med.kanazawa-u.ac.jp

Sponsor
Institute	Department of Neurology and Neurobiology of Aging, Kanazawa university Graduate School of Medical Science
Institute
Department

Funding Source
Organization	Japan Society for the Promotion of Science Japan Agency for Medical Research and Development
Organization
Division
Category of Funding Organization	Other
Nationality of Funding Organization	Japan

Other related organizations
Co-sponsor	Takasaki University of Health and welfare Tokyo University Graduate School of Agricaltural and Life Sciences
Name of secondary funder(s)

IRB Contact (For public release)
Organization
Address
Tel
Email

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

Other administrative information
Date of disclosure of the study information	2016 Year 03 Month 25 Day

Related information
URL releasing protocol
Publication of results	Unpublished

Result
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

Progress
Recruitment status	Terminated
Date of protocol fixation	2016 Year 02 Month 24 Day
Date of IRB	2016 Year 03 Month 04 Day
Anticipated trial start date	2016 Year 07 Month 01 Day
Last follow-up date	2021 Year 06 Month 30 Day
Date of closure to data entry
Date trial data considered complete
Date analysis concluded

Other
Other related information	The information of the clinical trial has been migrated to another database.

Management information
Registered date	2016 Year 03 Month 24 Day
Last modified on	2019 Year 05 Month 13 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000024900