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A Trial of Cilostazol in Patients With Mild Cognitive Impairment (COMCID)

Primary Purpose

Mild Cognitive Impairment

Status

Completed

Phase

Phase 2

Locations

Japan

Study Type

Interventional

Intervention

Cilostazol

Placebo

About this trial

This is an interventional treatment trial for Mild Cognitive Impairment

Eligibility Criteria

55 Years - 84 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Age between 55-84 (inclusive)
Study partner who sufficiently knows the daily life of the patient
Patients with MCI who satisfy the core clinical criteria of National Institute for Aging-Alzheimer Association for MCI (nearly equivalent to mild neurocognitive disorder in Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition) and who also satisfy the following three criteria:
i) Memory complaint by subject or study partner Type I: Memory complaint by subject that is verified by a study partner Type II: Otherwise, memory complaint by study partner with the evidence of memory impairment Note) Memory complaint by subject that is not verified by study partner will be excluded.
ii) Mini-Mental State Examination (MMSE) scores between 22 and 28 (inclusive) iii) Clinical Dementia Rating (CDR) = 0.5
Written informed consent provided for study participation

Exclusion Criteria:

Parkinson's disease, Huntington's disease, normal pressure hydrocephalus, progressive supranuclear palsy, epilepsy, multiple sclerosis, cerebral infection, or subsequent complication caused by head trauma.
Findings of multiple infarction, brain tumor, or subdural hematoma on MRI performed within 48 weeks before provisional registration.
Contraindications for MRI such as magnetic body or metal.
History of major depression or bipolar disorder within 48 weeks before provisional registration, alcohol or other substance abuse within 96 weeks before provisional registration, other diseases or unstable conditions.
Poorly controlled diabetes mellitus (HbA1c>9.0%).
Cognitive impairment due to deficiency of vitamin B12 or folate.
Neurosyphilis.
Cognitive impairment due to thyroid function abnormality.
Psychoactive drugs within 4 weeks before provisional registration.
Oral anticoagulants within 4 weeks before provisional registration.
Double antiplatelet therapy (cf. Aspirin, Clopidogrel but not Cilostazol) within 4 weeks before provisional registration.
Poorly controlled diabetes mellitus treated with insulin within 4 weeks before provisional registration.
Episode of hypoglycemic attack with loss of consciousness within 4 weeks before provisional registration.
Anti-dementia drugs within 4 weeks before provisional registration.
Participation in any other new drug study for Alzheimer's disease.
Current bleeding or bleeding disorders.
Congestive heart failure.
Coronary artery stenosis.
Sustained high blood pressure within 2 weeks before provisional registration.
History of drug hypersensitivity to Cilostazol.
The subject or the subject's spouse pregnant or breast-feeding at the time of provisional registration.
Difficulty in neuropsychological tests due to hearing or visual impairment.
Considered by the principal investigator to be ineligible.

Sites / Locations

National Cerebral and Cardiovascular Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Cilostazol 50mg B.I.D.

Placebo B.I.D.

Arm Description

After the registration, the Site Investigators should start protocol treatment within 28 days including the day of registration. Protocol treatment defines as follows; Investigational Treatment: Cilostazol 50mg B.I.D. p.o. 96 Weeks

After the registration, the Site Investigators should start protocol treatment within 28 days including the day of registration. Protocol treatment defines as follows; Comparative Treatment: Placebo B.I.D. p.o. 96 Weeks

Outcomes

Primary Outcome Measures

Change from baseline in Mini Mental State Examination (MMSE)

Secondary Outcome Measures

Conversion from MCI to All-cause Dementia

Dementia is diagnosed clinically when the patient meets core clinical criteria for dementia with reference to Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition.

Cognitive Decline on Clinical dementia rating-sum of boxes (CDR-SB)

Cognitive Decline on Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) 14

Cognitive Decline on Logical Memory subtest of the Wechsler Memory Scale-Revised (WMS-R)

Functional Decline on Alzheimer's disease Cooperative Study scale for activities of daily living in MCI (ADCS-MCI-ADL)

Hippocampal volume

Magnetization prepared rapid acquisition with gradient echo is used to assess hippocampal volume.

Full Information

NCT ID

NCT02491268

First Posted

July 1, 2015

Last Updated

December 2, 2020

Sponsor

National Cerebral and Cardiovascular Center, Japan

1. Study Identification

Unique Protocol Identification Number

NCT02491268

Brief Title

A Trial of Cilostazol in Patients With Mild Cognitive Impairment (COMCID)

Official Title

A Trial of Cilostazol for Prevention of Conversion From Mild Cognitive Impairment to Dementia

Study Type

Interventional

2. Study Status

Record Verification Date

December 2020

Overall Recruitment Status

Completed

Study Start Date

May 1, 2015 (Actual)

Primary Completion Date

August 14, 2020 (Actual)

Study Completion Date

December 1, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

National Cerebral and Cardiovascular Center, Japan

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

Epidemiological, clinicopathological and animal studies show that vascular disease in various forms contributes to cognitive decline. Increasing age is the strongest risk for dementia irrespective of whether it results from a vascular etiology or neurodegenerative disease processes such as in Alzheimer's disease (AD). AD and vascular cognitive impairment, the two most common causes of dementia, represent two extremes of a spectrum of disorders; however, a number of entities, which possess varying degrees of neurodegenerative and vascular pathologies, occur in between. The pure forms of the disorders are preferred for convenience to label, treat or manage but conditions within the spectrum are the norm rather than the exception as dementia advances. Therefore, combinatorial therapy directed at both vascular and neurodegenerative aspects of dementia is a promising approach for the treatment of dementia in the elderly. Cilostazol acts as an antiplatelet agent and has other pleiotropic effects based on phosphodiesterase-3-dependent mechanisms. Increasing evidence suggests that cilostazol offers endothelial protection, via pleiotropic effects. Intriguingly, cilostazol has been shown to decrease amyloid beta (Abeta) accumulation and protect Abeta-induced cognitive deficits in an experimental model. In a pilot study of 10 patients with moderate AD (mean MMSE score, 11.9 points) who received donepezil, cilostazol add-on treatment for 5-6 months demonstrated significantly increased MMSE score in comparison to baseline. Moreover, cilostazol was shown to be effective in preventing cognitive decline in patients with AD with cerebrovascular diseases, mild cognitive impairment (MCI), and mild dementia who received donepezil. These results highlight the need for a comprehensive prospective cohort study to analyze the effect of cilostazol on the preservation of cognitive function in patients with early-stage cognitive impairment, namely MCI.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Mild Cognitive Impairment

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

166 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Cilostazol 50mg B.I.D.

Arm Type

Experimental

Arm Description

Arm Title

Placebo B.I.D.

Arm Type

Placebo Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

Cilostazol

Intervention Type

Drug

Intervention Name(s)

Placebo

Primary Outcome Measure Information:

Title

Change from baseline in Mini Mental State Examination (MMSE)

Time Frame

96 weeks

Secondary Outcome Measure Information:

Title

Conversion from MCI to All-cause Dementia

Description

Dementia is diagnosed clinically when the patient meets core clinical criteria for dementia with reference to Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition.

Time Frame

up to 96 weeks

Title

Cognitive Decline on Clinical dementia rating-sum of boxes (CDR-SB)

Time Frame

baseline, 48 weeks, and 96 weeks

Title

Cognitive Decline on Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) 14

Time Frame

baseline, 48 weeks, and 96 weeks

Title

Cognitive Decline on Logical Memory subtest of the Wechsler Memory Scale-Revised (WMS-R)

Time Frame

baseline, 48 weeks, and 96 weeks

Title

Functional Decline on Alzheimer's disease Cooperative Study scale for activities of daily living in MCI (ADCS-MCI-ADL)

Time Frame

baseline, 48 weeks, and 96 weeks

Title

Hippocampal volume

Description

Magnetization prepared rapid acquisition with gradient echo is used to assess hippocampal volume.

Time Frame

baseline and 96 weeks

Other Pre-specified Outcome Measures:

Title

Cognitive Decline on Free and Cued Selective Reminding Test (FCSRT)

Time Frame

baseline, 48 weeks, and 96 weeks

Title

Cognitive Decline on Trail making test (TMT)

Time Frame

baseline, 48 weeks, and 96 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

55 Years

Maximum Age & Unit of Time

84 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Age between 55-84 (inclusive) Study partner who sufficiently knows the daily life of the patient Patients with MCI who satisfy the core clinical criteria of National Institute for Aging-Alzheimer Association for MCI (nearly equivalent to mild neurocognitive disorder in Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition) and who also satisfy the following three criteria: i) Memory complaint by subject or study partner Type I: Memory complaint by subject that is verified by a study partner Type II: Otherwise, memory complaint by study partner with the evidence of memory impairment Note) Memory complaint by subject that is not verified by study partner will be excluded. ii) Mini-Mental State Examination (MMSE) scores between 22 and 28 (inclusive) iii) Clinical Dementia Rating (CDR) = 0.5 Written informed consent provided for study participation Exclusion Criteria: Parkinson's disease, Huntington's disease, normal pressure hydrocephalus, progressive supranuclear palsy, epilepsy, multiple sclerosis, cerebral infection, or subsequent complication caused by head trauma. Findings of multiple infarction, brain tumor, or subdural hematoma on MRI performed within 48 weeks before provisional registration. Contraindications for MRI such as magnetic body or metal. History of major depression or bipolar disorder within 48 weeks before provisional registration, alcohol or other substance abuse within 96 weeks before provisional registration, other diseases or unstable conditions. Poorly controlled diabetes mellitus (HbA1c>9.0%). Cognitive impairment due to deficiency of vitamin B12 or folate. Neurosyphilis. Cognitive impairment due to thyroid function abnormality. Psychoactive drugs within 4 weeks before provisional registration. Oral anticoagulants within 4 weeks before provisional registration. Double antiplatelet therapy (cf. Aspirin, Clopidogrel but not Cilostazol) within 4 weeks before provisional registration. Poorly controlled diabetes mellitus treated with insulin within 4 weeks before provisional registration. Episode of hypoglycemic attack with loss of consciousness within 4 weeks before provisional registration. Anti-dementia drugs within 4 weeks before provisional registration. Participation in any other new drug study for Alzheimer's disease. Current bleeding or bleeding disorders. Congestive heart failure. Coronary artery stenosis. Sustained high blood pressure within 2 weeks before provisional registration. History of drug hypersensitivity to Cilostazol. The subject or the subject's spouse pregnant or breast-feeding at the time of provisional registration. Difficulty in neuropsychological tests due to hearing or visual impairment. Considered by the principal investigator to be ineligible.

Facility Information:

Facility Name

National Cerebral and Cardiovascular Center

City

Suita

State/Province

Osaka

ZIP/Postal Code

564-8565

Country

Japan

12. IPD Sharing Statement

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A Trial of Cilostazol in Patients With Mild Cognitive Impairment (COMCID)

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