Cilostazol Augmentation Study in Dementia

This study has been completed.
Sponsor:
Collaborator:
Korea OIAA
Information provided by (Responsible Party):
Jung-Seok Choi, Seoul National University Hospital
ClinicalTrials.gov Identifier:
NCT01409564
First received: August 3, 2011
Last updated: April 14, 2014
Last verified: April 2014
  Purpose

The purpose of this study is to examine the effects of cilostazol augmentation in mild to moderate Alzheimer disease patients with subcortical white matter hyperintensities (WMHI) treated by donepezil.

Dementia is the most disabling disease in the old age. The prevalence of dementia is 5-10% of the elders. AchEIs (donepezil, galantamine, rivastigmine) are used to treat mild to moderate dementia, but these drugs only relate to symptomatic improvement and the response rates are less than 30%.

Cilostazol is a cyclic adenosine monophosphate phosphodiesterase 3 inhibitor (PDE3I) and used as antiplatelet agent in subcortical vascular disease (WMHI). And it upregulates phosphorylation of cyclic adenosine monophosphate-pathway response element binding protein (CREB) which plays a crucial role in memory enhancement and synaptic plasticity related to neurodegeneration prevention.

The investigators will try cilostazol augmentation in dementia patients with WMHI receiving donepezil to see the addictive effects of cilostazol using cognitive tasks and PET imaging.


Condition Intervention Phase
Alzheimer's Dementia
Drug: Cilostazol
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Cilostazol Augmentation Study In Dementia (CASID): A Randomized, Placebo-controlled Pilot Study to Compare the Efficacy Between Donepezil Monotherapy and Cilostazol Augmentation Therapy in Alzheimer's Disease Patients With Subcortical White Matter Hyperintensities

Resource links provided by NLM:


Further study details as provided by Seoul National University Hospital:

Primary Outcome Measures:
  • Regionally Averaged Cerebral Glucose Uptake Changes Measured by FDG PET Uptake With Voxel-based Method [ Time Frame: Baseline, 24-week ] [ Designated as safety issue: No ]
    Regional cerebral glucose uptake level was measured as the ratio value of FDG uptake of the each unit level to the global mean uptake value.


Secondary Outcome Measures:
  • Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog) [ Time Frame: Baseline, 12-week, 24-week ] [ Designated as safety issue: No ]

    The ADAS-Cog score is measured by the number of questions answered incorrectly, therefore the higher is the worse.

    Score Scale: 0-75 (min-MAX)

    Each subcategory scores are summed.

    1. Word-recall test (0-10)
    2. Commands (0-5)
    3. Constructional praxis (0-5)
    4. Naming Objects/ Fingers (0-5)
    5. Ideational Praxis (0-5)
    6. Orientation (0-8)
    7. Word Recognition (0-12)
    8. Remembering Test Instructions (0-5)
    9. Spoken Language Ability (0-5)
    10. Word Finding Difficulty (0-5)
    11. Comprehension (0-5)

  • Mini-Mental State Examination (MMSE) in the Korean Version of the CERAD Assessment Packet) [ Time Frame: Baseline, 12-month, 24-month ] [ Designated as safety issue: No ]
    Basic cognitive functions are checked. (0-30) The score is better when higher.

  • Activities of Daily Living (ADCS-ADL) [ Time Frame: Baseline, 12-month, 24-month ] [ Designated as safety issue: No ]

    The caregiver answered to the questions given to measure the cognitive function level of the patients in daily living. Lower scores indicate greater severity.

    23 questions Score Scale: 0-78 (min-MAX)


  • Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB) [ Time Frame: Baseline, 12-month, 24-month ] [ Designated as safety issue: No ]

    Measured by professionally trained clinicians. Higher score indicates more severe AD symptoms.

    Score Scale: 0-18 (min-MAX)


  • Fazekas Scale [ Time Frame: Baseline ] [ Designated as safety issue: No ]

    Level of severity of white matter lesions in AD patients who can be legitimately administered with cilostazol. Measured by professionally trained clinicians.

    The higher score indicates more severe white matter lesion. Max-min: 0-3



Enrollment: 46
Study Start Date: May 2010
Study Completion Date: July 2013
Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cilostazol
Cilostazol group means dementia patients group receiving donepezil with cilostazol augmentation.
Drug: Cilostazol
Cilostazol 100mg bid per day will be administered orally and the period is total 24 weeks. The first week is a period for increasing the quantity, and during this period, cilostazol 50mg bid per day will be administered orally.
Placebo Comparator: Placebo
Placebo group means dementia patients group receiving donepezil with placebo.
Drug: Placebo
Placebo with similar shape and color to cilostazol 100mg bid per day will be administered orally and the period is total 24 weeks. The first week is a period for increasing the quantity, and during this period, placebo 50mg bid per day will be administered orally.

  Eligibility

Ages Eligible for Study:   60 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Men/women over sixty years old
  • Patients with slight and moderate dementia (MMSE score is over 10 under 26.)
  • Patients with probable Alzheimer's disease according to the standard of NINCDS-ADRDA
  • Patients accompanied with WMHI on Brain MRI (Fazeka's scale 1~3)

Exclusion Criteria:

  • Those who do not agree to the test in a written form
  • Patients who accompany other diseases except cerebral atrophy or change of subcortical white matter due to Alzheimer's disease on brain MRI
  • Patients who should not use Cilostazol (① patients with bleeding tendency ② patients with congestive heart failure ③ patients who have a medical history of hypersensitivity to this medicine or constituent of this medicine ④ those who use anticoagulant and clot buster)
  • Patients who suffer from nerve diseases or mental diseases which have influence on cognitive function except Alzheimer's disease (for example, schizophrenia, severe depression, mental retardation and etc.)
  • Patients who are suspected to have a personal history of drug addiction or alcoholism within recent 10 years
  • Patients who have severe problems in eye sight or hearing so that it is impossible to conduct the test smoothly
  • Patients who the researchers think are inappropriate for taking part in the test
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01409564

Locations
Korea, Republic of
SMG-SNU Boramae Medical Center
Seoul, Korea, Republic of, 156-707
Sponsors and Collaborators
Seoul National University Hospital
Korea OIAA
Investigators
Principal Investigator: Jung-Seok Choi, MD, PhD SMG-SNU Boramae Medical Center, Seoul, Republic of Korea
  More Information

No publications provided

Responsible Party: Jung-Seok Choi, Assistant Professor, Seoul National University Hospital
ClinicalTrials.gov Identifier: NCT01409564     History of Changes
Other Study ID Numbers: 06-2009-145
Study First Received: August 3, 2011
Results First Received: August 19, 2013
Last Updated: April 14, 2014
Health Authority: Korea: Food and Drug Administration

Keywords provided by Seoul National University Hospital:
Alzheimer's dementia
Cilostazol

Additional relevant MeSH terms:
Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Nervous System Diseases
Neurodegenerative Diseases
Tauopathies
Cilostazol
Anti-Asthmatic Agents
Autonomic Agents
Bronchodilator Agents
Cardiovascular Agents
Central Nervous System Agents
Enzyme Inhibitors
Fibrin Modulating Agents
Fibrinolytic Agents
Hematologic Agents
Molecular Mechanisms of Pharmacological Action
Neuroprotective Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Phosphodiesterase 3 Inhibitors
Phosphodiesterase Inhibitors
Physiological Effects of Drugs
Platelet Aggregation Inhibitors
Protective Agents
Respiratory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 29, 2014