Parkinson's DiseasePhase 3MUSTARDD-PDNCT01014858
Multi-centre UK Study of the Acetylcholinesterase Inhibitor Donepezil in Early Dementia Associated With Parkinson's Disease
A Phase 3 study testing Donepezil in people with Parkinson's Disease, run by Newcastle-upon-Tyne Hospitals NHS Trust at 22 sites in United Kingdom.
Trial summary
To demonstrate the superiority of donepezil over placebo in improving cognitive function, neuropsychiatric burden and functional ability in people with Parkinson's disease and mild dementia after 24 months of treatment. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Parkinson's Disease
- What is being tested?
- Donepezil
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 64 participants
- Where
- 22 sitesUnited Kingdom
- Study dates
- Jan 2013to Sep 2014
- Phase
- Phase 3
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- A diagnosis of Parkinson's disease according to UK Parkinson's Disease Society Brain Bank Criteria. These criteria are in standard use throughout the NHS in the UK and were supported by the NICE guidelines.
- 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). The ACE-R permits some description of the dementia profile and also quantifies global impairment. It is increasingly used by clinicians in the UK to identify demented subjects, is relatively quick to perform (15 minutes or so), requires no specific training and produces a total score (0-100), from which the MMSE (0-30) can also be extracted. 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 4 (corresponding to between the 6th and 28th percentile) will be used to define "mild" dementia".
- Community-living and a spouse, close relative or well established carer to accompany the subject to act as an informant.
- Where relevant, women of child bearing potential must be using adequate contraception for duration of study.
Who cannot join
- 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). This exclusion criterion is consistent with recommendations made in the Movement Disorder Society Dementia Task Force Diagnostic Criteria and the Third Report of the DLB Consortium.
- 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.
- Severe current depressive episode. Low mood may impact upon accurate cognitive assessment and major depression is therefore listed as a feature which, when present, makes it impossible to reliably diagnose PDD in the Movement disorder Society Task Force PDD Criteria. This will be operationalised using the self-completed Beck Depression Inventory and a cut-off score of 13, as recommended by a recent Movement Disorder Society Task Force report. The BDI score is considered robust in the face of mild to moderate cognitive impairment.
- Unstable significant medical co-morbidity.
- Patient receiving an anticholinergic drug for control of parkinsonian motor symptoms.
- Previous exposure to a cholinesterase inhibitor
Show all 10Show fewer
- Presence of a condition that is contraindicative to use of donepezil (including a clinically significant cardiac conduction defect found in patient history or from screening ECG); see SmPC (Appendix W) for details.
- Allergy/hypersensitivity to excipients of donepezil or placebo
- Patient receiving the N-methyl-d-aspartate antagonist memantine.
- Previous neurosurgery for Parkinson's disease. This will apply to only a small minority of predominantly younger cases. The main reason for this exclusion relates to ongoing uncertainty over the potential confounding effects of deep brain stimulation upon both mood and cognition.
Trial locations and contacts
22 sites in 1 country.
22 sites in 1 country
United Kingdom22 sites
Royal United Hospital (RUH) Bath NHS
Bath, BA1 3NG
Sandwell and West Birmingham NHS Foundation Trust
Birmingham, B18 7QH
Steps and Pines, Southmead Hospital
Bristol, BS10 5NB
Pennine Acute Hospitals NHS Trust
Bury, BL9 7TD
Cambridge Centre for Brain Repair
Cambridge, CB2 0PY
Dr Lakmali Sugathapala
Derby, DE22 3NE
Royal Bournemouth & Christchurch Hospitals NHS Foundation Trust
Dorset, BH23 2JX
NHS Greater Glasgow and Clyde
Glasgow, G51 4TF
Dr Pippa Metcalf
Gloucester, Gloucester
Llandudno Hospital, Betsi Cadwaladr University Health Board & School of Medical Sciences
Llandudno, LL30 1LB
King's College Hospital NHS Foundtion Trust
London, SE59RS
Manchester Mental Health & Social Care NHS Trust
Manchester, M8 5RB
Milton Keynes
Milton Keynes, MK6 5LD
Newcastle
Newcastle upon Tyne, Tyne and Wear, NE4 5PL
Royal Gwent Hospital
Newport, NP20 2UB
North Tyneside General Hospital
Northumberland, NE29 8NH
Norfolk and Norwich University Hospitals NHS Foundation Trust
Norwich, NR4 7UY
Oxford University Hospitals NHS Foundation Trust
Oxford, OX3 9DU
Plymouth Hospitals NHS Trust
Plymouth, PL6 8DH
Poole Hospital NHS Trust
Poole, BH15 2JB
Southampton General Hospital
Southampton, SO16 6YD
Dr Dhakam
Surrey, KT16 0PZ
About this study
To demonstrate the superiority of donepezil over placebo in improving cognitive function, neuropsychiatric burden and functional ability in people with Parkinson's disease and mild dementia after 24 months of treatment.
To demonstrate the superiority of donepezil over placebo in improving patient and carer quality of life and to establish the cost-effectiveness of donepezil.
To determine the instrument most suitable for evaluating change in cognition in people with Parkinson's disease and mild dementia.
- Conditions
- Parkinson's Disease
- Being tested
- Donepezil
- Keywords
- Parkinson's disease, mild dementia, donepezil, NIHR HTA
- Medical subject headings
- Parkinson Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DonepezilDrug
5mg donepezil daily for first 8 weeks and then increased to 10mg daily for the remainder of the study.
| Study group | Role | What they receive |
|---|---|---|
| Donepezil | Experimental | 5mg of Donepezil for the first 8 weeks raising to 10mg thereafter if patient adjusted to 5mg dose. 10mg does continues for the remainder of the study. Receives: Drug: Donepezil |
| Placebo | Placebo comparator | Patient commences medication to match appearance of 5mg donepezil for first 8 weeks then 10mg for the remainder of the study. Receives: Drug: Donepezil |
What is being measured
The primary outcome is the main question the study is designed to answer.
To demonstrate the superiority of donepezil over placebo in improving cognitive function, neuropsychiatric burden and functional ability in people with Parkinson's disease and mild dementia after 24 months of treatment.
Measured: After 24 month of treatment
Secondary outcomes (1)
To demonstrate the superiority of donepezil over placebo in improving patient and carer quality of life and to establish the cost-effectiveness of donepezil.
Measured: 26, 52 and 104 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Nov 2009 (estimated)
- Study startJan 2013
- Primary completionSep 2014
- Study completionSep 2014
Why it stopped: Due to low recruitment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Parkinson's DiseaseStudies 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 64 participants (actual)
Sponsor and investigators
- Lead sponsor
- Newcastle-upon-Tyne Hospitals NHS Trust
- Sponsor type
- University, hospital or other
- Collaborators
- University of Newcastle Upon-Tyne, University of Cambridge, University of Manchester, University of Birmingham, Bangor University, London School of Economics and Political Science, University College, London, Lancashire Care NHS Foundation Trust, Newcastle University, King's College London
- Responsible party
- Sponsor
- Investigators
- David J Burn, Professor, Study chair, Newcastle UniversityRoger A Barker, Dr, Study director, Cambridge UniversityBelinda Braithwaite, Mrs, Study director, lay personAlistair Burns, Professor, Study director, School of Community Based Medicine, University of ManchesterCarl E Clarke, Professor, Study director, ClarkeElaine McColl, Professor, Study director, University of Newcastle Upon-TyneJohn V Hindle, Dr, Study director, Llandudno Hospital & University of College WalesMartin Knapp, Professor, Study director, London School of Economics and Political Science
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01014858
- Sponsor's protocol ID
- 5137
- Other IDs
- 08/13/14
- Acronym
- MUSTARDD-PD
- Status last verified
- Sep 2017
- First submitted
- 16 Nov 2009
- Last updated
- 25 Sep 2017
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 25 Sep 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multi-centre UK Study of the Acetylcholinesterase Inhibitor Donepezil in Early Dementia Associated With Parkinson's Disease
- ClinicalTrials.gov ID
- NCT01014858
- Acronym / sponsor ID
- MUSTARDD-PD / 5137
- Conditions
- Parkinson's Disease
- Keywords
- Parkinson's disease, mild dementia, donepezil, NIHR HTA
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Due to low recruitment
- Enrolment
- 64 participants (actual)
- Lead sponsor
- Newcastle-upon-Tyne Hospitals NHS TrustUniversity, hospital or other
- Collaborators
- University of Newcastle Upon-Tyne, University of Cambridge, University of Manchester, University of Birmingham, Bangor University, London School of Economics and Political Science, University College, London, Lancashire Care NHS Foundation Trust, Newcastle University, King's College London
- Study start
- Jan 2013
- Primary completion
- Sep 2014 (actual)
- Study completion
- Sep 2014 (actual)
- First posted
- 17 Nov 2009 (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.
To demonstrate the superiority of donepezil over placebo in improving cognitive function, neuropsychiatric burden and functional ability in people with Parkinson's disease and mild dementia after 24 months of treatment.
To demonstrate the superiority of donepezil over placebo in improving patient and carer quality of life and to establish the cost-effectiveness of donepezil.
To determine the instrument most suitable for evaluating change in cognition in people with Parkinson's disease and mild dementia.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Donepezil | Experimental | Drug: Donepezil5mg of Donepezil for the first 8 weeks raising to 10mg thereafter if patient adjusted to 5mg dose. 10mg does continues for the remainder of the study. |
| Placebo | Placebo comparator | Drug: DonepezilPatient commences medication to match appearance of 5mg donepezil for first 8 weeks then 10mg for the remainder of the study. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- A diagnosis of Parkinson's disease according to UK Parkinson's Disease Society Brain Bank Criteria. These criteria are in standard use throughout the NHS in the UK and were supported by the NICE guidelines.
- 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). The ACE-R permits some description of the dementia profile and also quantifies global impairment. It is increasingly used by clinicians in the UK to identify demented subjects, is relatively quick to perform (15 minutes or so), requires no specific training and produces a total score (0-100), from which the MMSE (0-30) can also be extracted. 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 4 (corresponding to between the 6th and 28th percentile) will be used to define "mild" dementia".
- Community-living and a spouse, close relative or well established carer to accompany the subject to act as an informant.
- Where relevant, women of child bearing potential must be using adequate contraception for duration of study.
Key exclusion criteria (10 listed)
- 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). This exclusion criterion is consistent with recommendations made in the Movement Disorder Society Dementia Task Force Diagnostic Criteria and the Third Report of the DLB Consortium.
- 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.
- Severe current depressive episode. Low mood may impact upon accurate cognitive assessment and major depression is therefore listed as a feature which, when present, makes it impossible to reliably diagnose PDD in the Movement disorder Society Task Force PDD Criteria. This will be operationalised using the self-completed Beck Depression Inventory and a cut-off score of 13, as recommended by a recent Movement Disorder Society Task Force report. The BDI score is considered robust in the face of mild to moderate cognitive impairment.
- Unstable significant medical co-morbidity.
- Patient receiving an anticholinergic drug for control of parkinsonian motor symptoms.
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 |
|---|---|---|
| Donepezil5mg donepezil daily for first 8 weeks and then increased to 10mg daily for the remainder of the study. | Drug | Donepezil, Placebo |
Primary outcome
To demonstrate the superiority of donepezil over placebo in improving cognitive function, neuropsychiatric burden and functional ability in people with Parkinson's disease and mild dementia after 24 months of treatment.
Time frame: After 24 month of treatment
1 secondary outcome
To demonstrate the superiority of donepezil over placebo in improving patient and carer quality of life and to establish the cost-effectiveness of donepezil.
Time frame: 26, 52 and 104 weeks
Results and safety
The study was stopped early (reason given: Due to low recruitment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Sep 2017.
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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.
David J Burn, Professor study chair
Newcastle University
Roger A Barker, Dr study director
Cambridge University
Belinda Braithwaite, Mrs study director
lay person
22 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Donepezil in people with Parkinson's Disease, run by Newcastle-upon-Tyne Hospitals NHS Trust at 22 sites in United Kingdom.
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 4 inclusion and 10 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: stopped early, as of the sponsor's last update on 25 Sep 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 22 sites in United Kingdom. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 was stopped early (reason given: Due to low recruitment). Results are not available in the source record.
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?
To demonstrate the superiority of donepezil over placebo in improving cognitive function, neuropsychiatric burden and functional ability in people with Parkinson's disease and mild dementia after 24 months of treatment. (time frame: After 24 month of treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 25 Sep 2017.