Mild Cognitive ImpairmentPhase 2NCT02491268
A Trial of Cilostazol in Patients With Mild Cognitive Impairment (COMCID)
A Phase 2 study testing Cilostazol in people with Mild Cognitive Impairment, run by National Cerebral and Cardiovascular Center, Japan at 1 site in Japan.
Trial 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). Read more about this study
- Who is it for?
- Ages 55 to 84 years
- Conditions the study is for
- Mild Cognitive Impairment
- What is being tested?
- Cilostazol
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 166 participants
- Where
- 1 siteJapan
- Study dates
- 1 May 2015to 1 Dec 2020
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 55 to 84 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
- 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.
- 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
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Trial of Cilostazol for Prevention of Conversion From Mild Cognitive Impairment to Dementia
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.
- Conditions
- Mild Cognitive Impairment
- Being tested
- Cilostazol, Placebo
- Medical subject headings
- Cognitive Dysfunction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CilostazolDrug
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| Cilostazol 50mg B.I.D. | Experimental | 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 Receives: Drug: Cilostazol |
| Placebo B.I.D. | Placebo comparator | 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 Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline in Mini Mental State Examination (MMSE)
Measured: 96 weeks
Secondary outcomes (6)
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.
Measured: up to 96 weeks
Cognitive Decline on Clinical dementia rating-sum of boxes (CDR-SB)
Measured: baseline, 48 weeks, and 96 weeks
Cognitive Decline on Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) 14
Measured: baseline, 48 weeks, and 96 weeks
Cognitive Decline on Logical Memory subtest of the Wechsler Memory Scale-Revised (WMS-R)
Measured: baseline, 48 weeks, and 96 weeks
Functional Decline on Alzheimer's disease Cooperative Study scale for activities of daily living in MCI (ADCS-MCI-ADL)
Measured: baseline, 48 weeks, and 96 weeks
Hippocampal volume
Magnetization prepared rapid acquisition with gradient echo is used to assess hippocampal volume.
Measured: baseline and 96 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jul 2015 (estimated)
- Study start1 May 2015
- Primary completion14 Aug 2020
- Study completion1 Dec 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Mild Cognitive ImpairmentStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 166 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cerebral and Cardiovascular Center, Japan
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Masafumi Ihara, National Cerebral and Cardiovascular Center, Japan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02491268
- Sponsor's protocol ID
- TRINEU1321
- Status last verified
- Dec 2020
- First submitted
- 1 Jul 2015
- Last updated
- 4 Dec 2020
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Saito S, Suzuki K, Ohtani R, Maki T, Kowa H, Tachibana H, Washida K, Kawabata N, Mizuno T, Kanki R, Sudoh S, Kitaguchi H, Shindo K, Shindo A, Oka N, Yamamoto K, Yasuno F, Kakuta C, Kakuta R, Yamamoto Y, Hattori Y, Takahashi Y, Nakaoku Y, Tonomura S, Oishi N, Aso T, Taguchi A, Kagimura T, Kojima S, Taketsuna M, Tomimoto H, Takahashi R, Fukuyama H, Nagatsuka K, Yamamoto H, Fukushima M, Ihara M; COMCID Trial Investigator Group. Efficacy and Safety of Cilostazol in Mild Cognitive Impairment: A Randomized Clinical Trial. JAMA Netw Open. 2023 Dec 1;6(12):e2344938. doi: 10.1001/jamanetworkopen.2023.44938.
PubMed 38048134
Study at a glance
From the registry record, last updated by the sponsor on 4 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Trial of Cilostazol for Prevention of Conversion From Mild Cognitive Impairment to Dementia
- ClinicalTrials.gov ID
- NCT02491268
- Acronym / sponsor ID
- TRINEU1321
- Conditions
- Mild Cognitive Impairment
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 166 participants (actual)
- Lead sponsor
- National Cerebral and Cardiovascular Center, JapanUniversity, hospital or other
- Study start
- 1 May 2015 (actual)
- Primary completion
- 14 Aug 2020 (actual)
- Study completion
- 1 Dec 2020 (actual)
- First posted
- 8 Jul 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cilostazol 50mg B.I.D. | Experimental | Drug: CilostazolAfter 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 |
| Placebo B.I.D. | Placebo comparator | Drug: PlaceboAfter 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 |
Who may qualify
- Ages
- 55 to 84 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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:
- Written informed consent provided for study participation
Key exclusion criteria (23 listed)
- 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%).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cilostazol | Drug | Cilostazol 50mg B.I.D. |
| Placebo | Drug | Placebo B.I.D. |
Primary outcome
Change from baseline in Mini Mental State Examination (MMSE)
Time frame: 96 weeks
6 secondary outcomes
Conversion from MCI to All-cause Dementia
Time frame: up to 96 weeks
Cognitive Decline on Clinical dementia rating-sum of boxes (CDR-SB)
Time frame: baseline, 48 weeks, and 96 weeks
Cognitive Decline on Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) 14
Time frame: baseline, 48 weeks, and 96 weeks
Cognitive Decline on Logical Memory subtest of the Wechsler Memory Scale-Revised (WMS-R)
Time frame: baseline, 48 weeks, and 96 weeks
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
Hippocampal volume
Time frame: baseline and 96 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Dec 2020.
- Derived from this study: PubMed 38048134Saito S, Suzuki K, Ohtani R, Maki T, Kowa H, Tachibana H, Washida K, Kawabata N, Mizuno T, Kanki R, Sudoh S, Kitaguchi H, Shindo K, Shindo A, Oka N, Yamamoto K, Yasuno F, Kakuta C, Kakuta R, Yamamoto Y, Hattori Y, Takahashi Y, Nakaoku Y, Tonomura S, Oishi N, Aso T, Taguchi A, Kagimura T, Kojima S, Taketsuna M, Tomimoto H, Takahashi R, Fukuyama H, Nagatsuka K, Yamamoto H, Fukushima M, Ihara M; COMCID Trial Investigator Group. Efficacy and Safety of Cilostazol in Mild Cognitive Impairment: A Randomized Clinical Trial. JAMA Netw Open. 2023 Dec 1;6(12):e2344938. doi: 10.1001/jamanetworkopen.2023.44938.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Cilostazol in people with Mild Cognitive Impairment, run by National Cerebral and Cardiovascular Center, Japan at 1 site in Japan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change from baseline in Mini Mental State Examination (MMSE) (time frame: 96 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02491268, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Dec 2020.