Multi-centre UK Study of the Acetylcholinesterase Inhibitor Donepezil in Early Dementia Associated With Parkinson's Disease

Parkinson's Disease Clinical Trial

— MUSTARDD-PD  

Official title:

Multi-centre UK Study of the Acetylcholinesterase Inhibitor Donepezil in Early Dementia Associated With Parkinson's Disease

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01014858
• Other study ID #: 5137
• Secondary ID: 08/13/14
• Status: Terminated
• Phase: Phase 3
• First received: November 16, 2009
• Last updated: September 21, 2017
• Start date: January 2013
• Est. completion date: September 2014

Study information

• Verified date: September 2017
• Source: Newcastle-upon-Tyne Hospitals NHS Trust
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 64
• Est. completion date: September 2014
• Est. primary completion date: September 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. 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.

2. 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".

3. Community-living and a spouse, close relative or well established carer to accompany the subject to act as an informant.

4. Where relevant, women of child bearing potential must be using adequate contraception for duration of study.

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). 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.

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. 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.

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 found in patient history or from screening ECG); see SmPC (Appendix W) for details.

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. 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.

Related Conditions & MeSH terms

• Dementia
• Parkinson Disease
• Parkinson's Disease

Intervention

Drug:
• Donepezil
5mg donepezil daily for first 8 weeks and then increased to 10mg daily for the remainder of the study.

Locations

Country	Name	City	State
United Kingdom	Royal United Hospital (RUH) Bath NHS	Bath
United Kingdom	Sandwell and West Birmingham NHS Foundation Trust	Birmingham
United Kingdom	Steps and Pines, Southmead Hospital	Bristol
United Kingdom	Pennine Acute Hospitals NHS Trust	Bury
United Kingdom	Cambridge Centre for Brain Repair	Cambridge
United Kingdom	Dr Lakmali Sugathapala	Derby
United Kingdom	Royal Bournemouth & Christchurch Hospitals NHS Foundation Trust	Dorset
United Kingdom	NHS Greater Glasgow and Clyde	Glasgow
United Kingdom	Dr Pippa Metcalf	Gloucester
United Kingdom	Llandudno Hospital, Betsi Cadwaladr University Health Board & School of Medical Sciences	Llandudno
United Kingdom	King's College Hospital NHS Foundtion Trust	London
United Kingdom	Manchester Mental Health & Social Care NHS Trust	Manchester
United Kingdom	Milton Keynes	Milton Keynes
United Kingdom	Newcastle	Newcastle Upon Tyne	Tyne and Wear
United Kingdom	Royal Gwent Hospital	Newport
United Kingdom	North Tyneside General Hospital	Northumberland
United Kingdom	Norfolk and Norwich University Hospitals NHS Foundation Trust	Norwich
United Kingdom	Oxford University Hospitals NHS Foundation Trust	Oxford
United Kingdom	Plymouth Hospitals NHS Trust	Plymouth
United Kingdom	Poole Hospital NHS Trust	Poole
United Kingdom	Southampton General Hospital	Southampton
United Kingdom	Dr Dhakam	Surrey

Sponsors (11)

Lead Sponsor	Collaborator
Newcastle-upon-Tyne Hospitals NHS Trust	Bangor University, King's College London, Lancashire Care NHS Foundation Trust, London School of Economics and Political Science, Newcastle University, University College, London, University of Birmingham, University of Cambridge, University of Manchester, University of Newcastle Upon-Tyne

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.		After 24 month of treatment
Secondary	To demonstrate the superiority of donepezil over placebo in improving patient and carer quality of life and to establish the cost-effectiveness of donepezil.		26, 52 and 104 weeks