UMIN-CTR Clinical Trial

Public title

Delayed start study of donepezil hydrocloride for cognitive decline in Parkinson disease following EDAP-1

Acronym

EDAP-2

Scientific Title

Delayed start study of donepezil hydrocloride for cognitive decline in Parkinson disease following EDAP-1

Scientific Title:Acronym

EDAP-2

Region

Japan

Condition

Parkinson disease

Classification by specialty

Medicine in general

Neurology

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

To investigate the efficacy of donepezil hydrocloride against cognitive decline in patients who completed EDAP-1, by delayed start paradigm.

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Confirmatory

Trial characteristics_2

Developmental phase

Primary outcomes

Change of MMSE scores at the last visit from the basline scores of EDAP-1

Key secondary outcomes

Changes of Parkinson Psychosis Questionaire, Frontal Assessment Battery, and WMS-R from the baseline scores of EDAP-1

Study type

Interventional

Basic design

Single arm

Randomization

Non-randomized

Randomization unit

Blinding

Open -no one is blinded

Control

Uncontrolled

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

No. of arms

1

Purpose of intervention

Prevention

Type of intervention

Medicine

Interventions/Control_1

5mg donepezil hydrocloride

Interventions/Control_2

Interventions/Control_3

Interventions/Control_4

Interventions/Control_5

Interventions/Control_6

Interventions/Control_7

Interventions/Control_8

Interventions/Control_9

Interventions/Control_10

Age-lower limit

20

years-old

<=

Age-upper limit

Not applicable

Gender

Male and Female

Key inclusion criteria

1. Participants of EDAP-1 in Utano National Hosptial who have completed EDAP-1.
2. Both in-patients and out-patients.
3. Both females and males.
4. Age of 20 or elder (at IC obtaining)
5. Patients who give written informed consent.
6. Patients who are able to follow the study principles and to report their symptoms.

Key exclusion criteria

1. Past use of donepezil hydrochloride.
2. Use of an inhibitor of brain acetylcholine esterase (listed in the protocol) in the 4 weeks before Visit 2.
3.Patients who are diagnosed as possible or probable diffuse Lewy body disease according to the diagnostic criteria (shown in the protocol).
4.. Patients who have been diagnosed as schizophrenia.
5. Patients with previous history of the stereotaxic brain operation.
6. Patients with allergy to pyperidium derivatives.
7. Severe hepatic or renal dysfunction.
8. Patients with sick sinus syndrome or intra-atrial or AV nodal block (such as SA block or AV block of grade II or severer).
9. Patients with present or previous illness of severe gastrointestinal ulcer, severe bronchial asthma, or obstructive pulmonary disease.
10. Bradycardia (heart rate: 45 /min or less.) in the ECG at Visit 1.
11. QT elongation (QTc: >460msec) in the ECG at Visit 1.
12. Patients who are pregnant or feeding a baby.
13.Patients who are diagnosed as having malignancy
14. Patients who are judged as inappropriate for the enrolling to the trial by investigators.

Target sample size

50

Name of lead principal investigator

1st name	Hideyuki
Middle name
Last name	Sawada

Organization

National Hospital of Utano

Division name

Clinical Research Center

Zip code

616-8255

Address

8 Ondoyama-cho, Narutaki, Ukyoku, Kyoto

TEL

075-561-5121

Email

sawada@unh.hosp.go.jp

Name of contact person

1st name	Hideyuki
Middle name
Last name	Sawada

Organization

National Hospital of Utano

Division name

Clinical Research Center

Zip code

616-8255

Address

8 Ondoyama-cho, Narutaki, Ukyoku, Kyoto

TEL

075-461-5121

Homepage URL

Email

sawada.unh@gmail.com

Institute

National Hospital of Utano

Institute

Department

Personal name

Organization

National Hospital Organization

Organization

Division

Category of Funding Organization

Government offices of other countries

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

National Hopsital Organization, Utano National Hospital

Address

8 Ondoyamacho, Narutaki, Ukyoku, Kyoto

Tel

81-75-461-5121

Email

sawada.unh@gmail.com

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

Date of disclosure of the study information

2013

Year

05

Month

22

Day

URL releasing protocol

https://www.tandfonline.com/doi/abs/10.1080/14656566.2020.1814255

Publication of results

Published

URL related to results and publications

https://www.tandfonline.com/doi/abs/10.1080/14656566.2020.1814255

Number of participants that the trial has enrolled

98

Results

MMSE change at week 120 was better in the
early-start group than in the delayed-start
group, but the difference was not
significant. The MMSE declined in
apolipoprotein e4 carriers, but not in
non-carriers, and the factor interaction
(intervention x e4 genotype) was highly
significant (P < 0.001). Analyzed with the
interaction, the difference was significant (group difference 1.95 [0.33 to 3.57], P = 0.018).

Results date posted

2020

Year

09

Month

07

Day

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

The demographic and clinical features of the two groups were similar. Dopamine is associated with cognitive motivation in Parkinson disease 25. The dose of dopamine replacement therapy is shown in Table 1, and it was similar between the early-start and delayed-start groups. The mean (SD) baseline MMSE was 27.6 (2.0) in the early-start group and 28.0 (2.1) in the delayed-start group, and the percentage of apolipoprotein e4 carriers was 27.1% and 26.0%, respectively.

Participant flow

A total of 137 eligible patients were invited to participate in phase 1, and 108 patients gave consent between 1 April 2011 and 28 March 2012. Excluding 10 patients who were found to be ineligible, 98 patients were randomized to early-start (donepezil-to-donepezil, 48 patients) and delayed-start (placebo-to-donepezil, 50 patients) groups. Among the 48 patients in the early-start group, 29 completed phase 1, and 25 gave consent to phase 2. Among the 50 patients in the delayed-start group, 36 completed phase 1, and 23 gave consent to phase 2. In phase 2, five patients were discontinued due to consent withdrawal (three patients in the early-start and two patients in the delayed groups) and the data of 43 patients (22 in the early-start and 23 in the delayed-start) were analyzed with the intention-to-treat principle for the primary outcome measure.

Adverse events

The most common adverse events in phase 2 were hallucinations (12 events) and delusions (4 events), and the prevalence was higher in the early-start group than in the delayed-start group.

Outcome measures

In the early-start group, MMSE scores were stable in phase 1 and slightly higher in phase 2. In contrast, the scores in the delayed-start group decreased gradually throughout phase 1 and slightly increased in phase 2 (Figure 2A). At the end of phase 1, the estimated change in MMSE was -0.45 (-1.69 to 0.80) and -1.87 (-2.88 to -0.87) in the early-start and placebo groups, and the estimated group difference (SEM) was 1.43 (0.82) (P = 0.081). The change in MMSE score at week 120 was better in the early-start group than in the delayed-start group; however, the difference was not statistically significant.

Plan to share IPD

IPD sharing Plan description

Recruitment status

Completed

Date of protocol fixation

2013

Year

02

Month

15

Day

Date of IRB

2013

Year

02

Month

21

Day

Anticipated trial start date

2013

Year

04

Month

10

Day

Last follow-up date

2014

Year

11

Month

10

Day

Date of closure to data entry

2014

Year

11

Month

30

Day

Date trial data considered complete

2014

Year

12

Month

10

Day

Date analysis concluded

Other related information

Registered date

2013

Year

05

Month

22

Day

Last modified on

2020

Year

09

Month

07

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000012611