Condition category
Nervous System Diseases
Date applied
08/07/2009
Date assigned
07/08/2009
Last edited
19/04/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
Every day in the UK, between 30 and 40 people are told they have Parkinson's disease. Of these, nearly four-fifths will go on to develop dementia. The symptoms of dementia, which include hallucinations, also put a huge additional strain on the person's family. Parkinson's disease is a very costly disease in the UK and when dementia occurs it is likely to increase the healthcare costs even further. Whilst drug treatments have made a big impact in treating the motor symptoms of Parkinson's disease (slowness, stiffness and tremor), the management of dementia is woefully inadequate. We wish to test the effectiveness of a drug called donepezil in people with dementia associated with Parkinson's disease. Donepezil and similar drugs cost the NHS around £1200 per year to prescribe for each patient. It is therefore important to learn whether donepezil produces benefits that are truly meaningful to patients and their families, whilst also being good value for money. In this study the participants will have only mild symptoms of dementia when they are approached to consider taking part. By treating at this stage, we will be able to assess the effect of early intervention.

Who can participate?
Patients aged 18 or over with Parkinson's disease and mild dementia

What does the study involve?
Participants are randomly allocated to receive either donepezil or an identical tablet, called a placebo, which contains no active drug. Participants take the tablets for up to two years. The results are then compared to see if one treatment is better than the other. We measure cognition (memory and attention), psychiatric disturbances (for example, visual hallucinations) and changes in patient and carer quality of life. We also look at the services people use, their costs, and the time spent by family members providing unpaid care, so that we can determine whether the treatment is good value for money.

What are the possible benefits and risks of participating?
Not provided at time of registration

Where is the study run from?
Newcastle University (UK)

When is the study starting and how long is it expected to run for?
November 2009 to October 2014

Who is funding the study?
NIHR Health Technology Assessment Programme - HTA (UK)

Who is the main contact?
Prof. David Burn
d.j.burn@ncl.ac.uk

Trial website

Contact information

Type

Scientific

Primary contact

Prof David Burn

ORCID ID

Contact details

Clinical Ageing Research Unit
Campus for Ageing and Vitality
Newcastle upon Tyne
NE4 5PL
United Kingdom
+44 (0)191 248 1266
d.j.burn@ncl.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

HTA 08/14/13; Protocol 1.0

Study information

Scientific title

Multicentre UK study of the acetylcholinesterase inhibitor donepezil in early dementia associated with Parkinson's disease

Acronym

MUSTARDD-PD

Study hypothesis

Primary hypothesis:
That donepezil is superior to placebo in improving cognitive function, neuropsychiatric burden and functional ability in people with Parkinson's disease and mild dementia after 24 months of treatment.

Secondary hypotheses:
1. That donepezil is superior to placebo in improving patient and carer quality of life
2. That donepezil is a cost-effective treatment option

More details can be found at: http://www.nets.nihr.ac.uk/projects/hta/081413
Protocol can be found at: http://www.nets.nihr.ac.uk/__data/assets/pdf_file/0003/81372/PRO-08-14-13.pdf

Ethics approval

Not provided at time of registration

Study design

Randomised double-blind placebo-controlled study

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Parkinson's disease with mild dementia

Intervention

Treatment group: donepezil orally, 5 mg once a day for 8 weeks, then 10 mg once a day (presented in both cases as 1 capsule) for up to 96 weeks.
Control group: matched placebo orally, 1 capsule daily for up to 104 weeks.

Total duration of treatment: maximum of 2 years (104 weeks). Total duration of follow-up: 2 years (i.e. to end of treatment period).

Intervention type

Drug

Phase

Phase III

Drug names

Donepezil

Primary outcome measures

1. Mattis Dementia Rating Scale (DRS-2)
2. Neuropsychiatric Inventory
3. Bristol Activity of Daily Living Scale

All primary and secondary outcome measures will be measured at baseline (commencement of treatment), 26 weeks, 52 weeks, 76 weeks and 104 weeks (+/- 7 days for each visit). The primary analysis will focus on outcomes at 104 weeks.

Secondary outcome measures

1. Quality of life via:
1.1. European Quality of Life questionnaire (EQ5D)
1.2. Dementia Quality of Life (DEMQOL)
1.3. DEMQOL-proxy
2. Costs via Client Service Receipt Inventory

All primary and secondary outcome measures will be measured at baseline (commencement of treatment), 26 weeks, 52 weeks, 76 weeks and 104 weeks (+/- 7 days for each visit). The primary analysis will focus on outcomes at 104 weeks.

Overall trial start date

01/11/2009

Overall trial end date

31/10/2014

Reason abandoned

Eligibility

Participant inclusion criteria

1. Aged greater than or equal to 18 years, no upper age limit, either sex
2. A diagnosis of Parkinson's disease according to UK Parkinson's Disease Society Brain Bank Criteria
3. People with mild dementia associated with PD, where the patient and/or their family have become aware of cognitive with or without behavioural symptoms that are causing functional impairment. "Dementia" will be defined according to recently published Movement Disorder Society Task Force criteria for dementia associated with Parkinson's disease and "operationalised" using the Addenbrooke's Cognitive Examination (ACE-R). Participants will have an ACE-R of 88 or less. If this criterion is met, subjects will be further assessed using the Mattis Dementia Rating Scale (DRS-2). An age- and education-corrected total DRS-2 score of less than 8 but greater than 6 (corresponding to between the 6th and 28th percentile) will be used to define "mild" dementia.
4. Community-living and a spouse, close relative or well established informal carer to accompany the subject to act as an informant
5. Where relevant, women of child bearing potential must be using adequate contraception for duration of study

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

500

Participant exclusion criteria

1. Dementia that develops within one year of the onset of motor symptoms. The reason for this "one year rule" is to specifically exclude participants with Dementia with Lewy Bodies (DLB).
2. People with such severe motor disability, or who are so impaired in their activities of daily living from other aspects of their PD, that it would interfere with cognitive and global assessments
3. Severe current depressive episode. This will be operationalised using the self-completed Beck Depression Inventory and a cut-off score of 13/14.
4. Unstable significant medical co-morbidity
5. Patient receiving an anticholinergic drug for control of parkinsonian motor symptoms
6. Previous exposure to a cholinesterase inhibitor
7. Presence of a condition that is contraindicative to use of donepezil (including a clinically significant cardiac conduction defect)
8. Allergy/hypersensitivity to excipients of donepezil or placebo
9. Patient receiving the N-methyl-d-aspartate antagonist memantine
10. Previous neurosurgery for Parkinson's disease

Recruitment start date

01/11/2009

Recruitment end date

31/10/2014

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Clinical Ageing Research Unit
Newcastle upon Tyne
NE4 5PL
United Kingdom

Sponsor information

Organisation

Newcastle upon Tyne Hospitals NHS Foundation Trust (UK)

Sponsor details

Joint Research Office
4th Floor
Leazes Wing
Royal Victoria Infirmary
Queen Victoria Road
Newcastle upon Tyne
NE1 4LP
United Kingdom

Sponsor type

Government

Website

http://www.newcastle-hospitals.org.uk/about-us/staff-information_research-development.aspx

Funders

Funder type

Government

Funder name

NIHR Health Technology Assessment Programme - HTA (UK)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

01/08/2015

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

19/04/2016: Plain English summary added.