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

Condition(s) targeted: Parkinson's Disease

Intervention: Donepezil (Drug)

Phase: Phase 3

Status: Not yet recruiting

Sponsored by: Sharon Erb

Official(s) and/or principal investigator(s):
David J Burn, Professor, Study Chair, Affiliation: Institute for Ageing and Health, Newcastle University
Roger A Barker, Dr, Study Director, Affiliation: Cambridge University
Belinda Braithwaite, Mrs, Study Director, Affiliation: lay person
Alistair Burns, Professor, Study Director, Affiliation: School of Community Based Medicine, University of Manchester
Carl E Clarke, Professor, Study Director, Affiliation: Clarke
Elaine McColl, Professor, Study Director, Affiliation: University of Newcastle Upon-Tyne
John V Hindle, Dr, Study Director, Affiliation: Llandudno Hospital & University of College Wales
Martin Knapp, Professor, Study Director, Affiliation: London School of Economics and Political Science
Andrew J Lees, Professor, Study Director, Affiliation: University College, London
Iracema Leroi, DR, Study Director, Affiliation: Lancashire Care Trust, Royal Blackburn Hospital
Ian G McKeith, Professor, Study Director, Affiliation: Institute for Ageing and Health, Newcastle University
John T O'Brien, Professor, Study Director, Affiliation: Institute for Ageing and Health, Newcastle University
Keith Wheatley, Professor, Study Director, Affiliation: Cancer Research UK Clinical Trials Unit, School of Cancer Sciences, University of Birmingham
Ian N Steen, Dr, Study Director, Affiliation: University of Newcastle Upon-Tyne
Jennifer Wilkinson, Mrs, Study Director, Affiliation: University of Newcastle Upon-Tyne
Sharon Erb, Mrs, Study Director, Affiliation: University of Newcastle Upon-Tyne

Overall contact:
David J Burn, Professor, Phone: +44 (0)191 2481266, Email: d.j.burn@ncl.ac.uk

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.

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

Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

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.

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.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

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 6 (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.

David J Burn, Professor, Phone: +44 (0)191 2481266, Email: d.j.burn@ncl.ac.uk

Starting date: May 2012
Last updated: April 27, 2012