Trial Outcomes & Findings for Cilostazol Augmentation Study in Dementia (NCT NCT01409564)

NCT ID: NCT01409564

Last Updated: 2014-05-13

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 46 participants
• Primary outcome timeframe: Baseline, 24-week
• Results posted on: 2014-05-13

Participant Flow

46 Subjects were enrolled in the single center of Seoul National University Boramae Hospital. The diagnosis of probable AD was made according to the criteria of NINCDS-ADRDA (MMSE score 10 ~ 26). Enrollment has started in July 2010 to end in March 2012.

Participant milestones

Measure	Cilostazol Cilostazol group includes dementia patients receiving donepezil with cilostazol augmentation. All the randomly assigned AD patients in cilostazol group received 10 mg of Donepezil along with 200 mg of cilostazol per a day, doubly blinded. All the medications were orally administered. For the initial two weeks, patients only received 100 mg of cilstazol per a day to minimize the instabilities. Afterwards, for 22 weeks, patients received 200 mg of cilostazol.	Placebo Placebo group includes dementia patients receiving donepezil with placebo. All the patients were randomly assigned as placebo group and received 10 mg of Donepezil along with the same dose of sugar pill as normal cilostazol. All the clinical assessments and medications were doubly blinded. All the medications were orally administered.
Overall Study STARTED	23	23
Overall Study COMPLETED	18	18
Overall Study NOT COMPLETED	5	5

Reasons for withdrawal

Measure	Cilostazol Cilostazol group includes dementia patients receiving donepezil with cilostazol augmentation. All the randomly assigned AD patients in cilostazol group received 10 mg of Donepezil along with 200 mg of cilostazol per a day, doubly blinded. All the medications were orally administered. For the initial two weeks, patients only received 100 mg of cilstazol per a day to minimize the instabilities. Afterwards, for 22 weeks, patients received 200 mg of cilostazol.	Placebo Placebo group includes dementia patients receiving donepezil with placebo. All the patients were randomly assigned as placebo group and received 10 mg of Donepezil along with the same dose of sugar pill as normal cilostazol. All the clinical assessments and medications were doubly blinded. All the medications were orally administered.
Overall Study low medication compliance	4	3
Overall Study brain abnormalities found in T1 MR	1	2

Baseline Characteristics

Cilostazol Augmentation Study in Dementia

Baseline characteristics by cohort

Measure	Cilostazol n=18 Participants Cilostazol group means dementia patients group receiving donepezil with cilostazol augmentation.	Placebo n=18 Participants Placebo group means dementia patients group receiving donepezil with placebo.	Total n=36 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical >=65 years	18 Participants n=5 Participants	18 Participants n=7 Participants	36 Participants n=5 Participants
Age, Continuous	79.00 years STANDARD_DEVIATION 6.26 • n=5 Participants	78.05 years STANDARD_DEVIATION 6.09 • n=7 Participants	78.53 years STANDARD_DEVIATION 6.11 • n=5 Participants
Sex: Female, Male Female	13 Participants n=5 Participants	15 Participants n=7 Participants	28 Participants n=5 Participants
Sex: Female, Male Male	5 Participants n=5 Participants	3 Participants n=7 Participants	8 Participants n=5 Participants
Region of Enrollment Korea, Republic of	18 participants n=5 Participants	18 participants n=7 Participants	36 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, 24-week

Population: Number of patients with increased whole brain glucose uptake level. In the real analysis, however, a voxel-based image analysis results were used; therefore, data which can be entered here is not much meaningful.

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.

Outcome measures

Measure	Cilostazol, Baseline n=18 Participants Cilostazol group means dementia patients group receiving donepezil with cilostazol augmentation at the baseline.	Cilostazol, 24-week n=18 Participants Cilostazol group means dementia patients group receiving donepezil with cilostazol augmentation after 24 weeks.	Placebo, Baseline n=18 Participants Placebo group means dementia patients group receiving donepezil with placebo at the baseline.	Placebo, 24-week n=18 Participants Placebo group means dementia patients group receiving donepezil with placebo after 24 weeks.
Regionally Averaged Cerebral Glucose Uptake Changes Measured by FDG PET Uptake With Voxel-based Method Left Parietal Lobe	81.70 Bq/Bq (no unit) Standard Deviation 9.51	80.40 Bq/Bq (no unit) Standard Deviation 8.27	84.60 Bq/Bq (no unit) Standard Deviation 7.47	81.33 Bq/Bq (no unit) Standard Deviation 6.82
Regionally Averaged Cerebral Glucose Uptake Changes Measured by FDG PET Uptake With Voxel-based Method Right Parietal Lobe	80.03 Bq/Bq (no unit) Standard Deviation 10.26	79.00 Bq/Bq (no unit) Standard Deviation 9.55	85.29 Bq/Bq (no unit) Standard Deviation 8.62	81.91 Bq/Bq (no unit) Standard Deviation 8.37
Regionally Averaged Cerebral Glucose Uptake Changes Measured by FDG PET Uptake With Voxel-based Method Left Inferior Frontal Gyrus	85.74 Bq/Bq (no unit) Standard Deviation 7.03	86.82 Bq/Bq (no unit) Standard Deviation 6.06	85.97 Bq/Bq (no unit) Standard Deviation 5.72	83.12 Bq/Bq (no unit) Standard Deviation 5.81
Regionally Averaged Cerebral Glucose Uptake Changes Measured by FDG PET Uptake With Voxel-based Method Right Inferior Frontal Gyrus	72.11 Bq/Bq (no unit) Standard Deviation 6.48	71.39 Bq/Bq (no unit) Standard Deviation 4.82	74.02 Bq/Bq (no unit) Standard Deviation 6.38	71.44 Bq/Bq (no unit) Standard Deviation 5.53

SECONDARY outcome

Timeframe: Baseline, 12-week, 24-week

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)

Outcome measures

Measure	Cilostazol, Baseline n=18 Participants Cilostazol group means dementia patients group receiving donepezil with cilostazol augmentation at the baseline.	Cilostazol, 24-week n=18 Participants Cilostazol group means dementia patients group receiving donepezil with cilostazol augmentation after 24 weeks.	Placebo, Baseline Placebo group means dementia patients group receiving donepezil with placebo at the baseline.	Placebo, 24-week Placebo group means dementia patients group receiving donepezil with placebo after 24 weeks.
Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog) Baseline	29.28 units on a scale Standard Deviation 8.79	27.78 units on a scale Standard Deviation 7.89	—	—
Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog) 12-week	26.33 units on a scale Standard Deviation 6.75	24.83 units on a scale Standard Deviation 7.67	—	—
Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog) 24-week	25.78 units on a scale Standard Deviation 8.19	24.78 units on a scale Standard Deviation 7.41	—	—

SECONDARY outcome

Timeframe: Baseline, 12-month, 24-month

Basic cognitive functions are checked. (0-30) The score is better when higher.

Outcome measures

Measure	Cilostazol, Baseline n=18 Participants Cilostazol group means dementia patients group receiving donepezil with cilostazol augmentation at the baseline.	Cilostazol, 24-week n=18 Participants Cilostazol group means dementia patients group receiving donepezil with cilostazol augmentation after 24 weeks.	Placebo, Baseline Placebo group means dementia patients group receiving donepezil with placebo at the baseline.	Placebo, 24-week Placebo group means dementia patients group receiving donepezil with placebo after 24 weeks.
Mini-Mental State Examination (MMSE) in the Korean Version of the CERAD Assessment Packet) Baseline	15.11 units on a scale Standard Deviation 3.61	15.44 units on a scale Standard Deviation 3.96	—	—
Mini-Mental State Examination (MMSE) in the Korean Version of the CERAD Assessment Packet) 12-week	16.67 units on a scale Standard Deviation 4.04	15.83 units on a scale Standard Deviation 4.84	—	—
Mini-Mental State Examination (MMSE) in the Korean Version of the CERAD Assessment Packet) 24-week	15.39 units on a scale Standard Deviation 3.94	16.22 units on a scale Standard Deviation 4.91	—	—

SECONDARY outcome

Timeframe: Baseline, 12-month, 24-month

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)

Outcome measures

Measure	Cilostazol, Baseline n=18 Participants Cilostazol group means dementia patients group receiving donepezil with cilostazol augmentation at the baseline.	Cilostazol, 24-week n=18 Participants Cilostazol group means dementia patients group receiving donepezil with cilostazol augmentation after 24 weeks.	Placebo, Baseline Placebo group means dementia patients group receiving donepezil with placebo at the baseline.	Placebo, 24-week Placebo group means dementia patients group receiving donepezil with placebo after 24 weeks.
Activities of Daily Living (ADCS-ADL) Baseline	50.17 units on a scale Standard Deviation 11.61	53.56 units on a scale Standard Deviation 14.86	—	—
Activities of Daily Living (ADCS-ADL) 12-week	48.00 units on a scale Standard Deviation 13.14	49.33 units on a scale Standard Deviation 17.38	—	—
Activities of Daily Living (ADCS-ADL) 24-week	46.33 units on a scale Standard Deviation 15.88	51.17 units on a scale Standard Deviation 16.53	—	—

SECONDARY outcome

Timeframe: Baseline, 12-month, 24-month

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

Score Scale: 0-18 (min-MAX)

Outcome measures

Measure	Cilostazol, Baseline n=18 Participants Cilostazol group means dementia patients group receiving donepezil with cilostazol augmentation at the baseline.	Cilostazol, 24-week n=18 Participants Cilostazol group means dementia patients group receiving donepezil with cilostazol augmentation after 24 weeks.	Placebo, Baseline Placebo group means dementia patients group receiving donepezil with placebo at the baseline.	Placebo, 24-week Placebo group means dementia patients group receiving donepezil with placebo after 24 weeks.
Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB) Baseline	5.11 units on a scale Standard Deviation 2.30	4.72 units on a scale Standard Deviation 1.56	—	—
Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB) 12-week	5.42 units on a scale Standard Deviation 2.05	5.28 units on a scale Standard Deviation 2.18	—	—
Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB) 24-week	5.44 units on a scale Standard Deviation 2.49	5.33 units on a scale Standard Deviation 2.88	—	—

SECONDARY outcome

Timeframe: Baseline

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

Outcome measures

Measure	Cilostazol, Baseline n=18 Participants Cilostazol group means dementia patients group receiving donepezil with cilostazol augmentation at the baseline.	Cilostazol, 24-week n=18 Participants Cilostazol group means dementia patients group receiving donepezil with cilostazol augmentation after 24 weeks.	Placebo, Baseline Placebo group means dementia patients group receiving donepezil with placebo at the baseline.	Placebo, 24-week Placebo group means dementia patients group receiving donepezil with placebo after 24 weeks.
Fazekas Scale Number of Patients Scored 1	13 participants	11 participants	—	—
Fazekas Scale Number of Patients Scored 2	3 participants	5 participants	—	—
Fazekas Scale Number of Patients Scored 3	2 participants	2 participants	—	—

Adverse Events

Cilostazol

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Cilostazol n=18 participants at risk Cilostazol group means dementia patients group receiving donepezil with cilostazol augmentation.	Placebo n=18 participants at risk Placebo group means dementia patients group receiving donepezil with placebo.
General disorders Nausea, Dizziness	5.6% 1/18 • Number of events 1	0.00% 0/18
Gastrointestinal disorders GI discomfort	5.6% 1/18 • Number of events 1	0.00% 0/18
General disorders Diarrhea	5.6% 1/18 • Number of events 1	0.00% 0/18
Vascular disorders Hypertension	5.6% 1/18 • Number of events 1	0.00% 0/18
Psychiatric disorders Depression	0.00% 0/18	5.6% 1/18 • Number of events 1
General disorders Vomiting	0.00% 0/18	5.6% 1/18 • Number of events 1
General disorders Headache	0.00% 0/18	5.6% 1/18 • Number of events 1

Additional Information

Prof. Jung Seok Choi

Seoul National University Hospital

Phone: 82-2-870-3461

Email: choijs@neuroimage.snu.ac.kr

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place