Clinical trial NCT01014858: Multi-centre UK Study of the Acetylcholinesterase Inhibitor Donepezil in Early Dementia Associated With Parkinson's Disease
Official title: Multi-centre UK Study of the Acetylcholinesterase Inhibitor Donepezil in Early Dementia Associated With Parkinson's Disease
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Parkinson's Disease
Keywords: Parkinson's disease
mild dementia
donepezil
NIHR HTA
Lead sponsor: Newcastle-upon-Tyne Hospitals NHS Trust
Sponsor class: OTHER
Collaborators: name: University of Newcastle Upon-Tyne
name: University of Cambridge
name: University of Manchester
name: University of Birmingham
name: Bangor University
name: London School of Economics and Political Science
name: University College, London
name: Lancashire Care NHS Foundation Trust
name: Newcastle University
name: King's College London
First posted: 2009-11-17
Enrollment: 64
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility 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 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.

Primary outcomes:
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.
timeFrame: After 24 month of treatment
Secondary outcomes:
measure: To demonstrate the superiority of donepezil over placebo in improving patient and carer quality of life and to establish the cost-effectiveness of donepezil.
timeFrame: 26, 52 and 104 weeks
Other outcomes:
Locations:
city: Newcastle Upon Tyne
country: United Kingdom
facility: Newcastle
state: Tyne and Wear
city: Bath
country: United Kingdom
facility: Royal United Hospital (RUH) Bath NHS
city: Birmingham
country: United Kingdom
facility: Sandwell and West Birmingham NHS Foundation Trust
city: Bristol
country: United Kingdom
facility: Steps and Pines, Southmead Hospital
city: Bury
country: United Kingdom
facility: Pennine Acute Hospitals NHS Trust
city: Cambridge
country: United Kingdom
facility: Cambridge Centre for Brain Repair
city: Derby
country: United Kingdom
facility: Dr Lakmali Sugathapala
city: Dorset
country: United Kingdom
facility: Royal Bournemouth & Christchurch Hospitals NHS Foundation Trust
city: Glasgow
country: United Kingdom
facility: NHS Greater Glasgow and Clyde
city: Gloucester
country: United Kingdom
facility: Dr Pippa Metcalf
city: Llandudno
country: United Kingdom
facility: Llandudno Hospital, Betsi Cadwaladr University Health Board & School of Medical Sciences
city: London
country: United Kingdom
facility: King's College Hospital NHS Foundtion Trust
city: Manchester
country: United Kingdom
facility: Manchester Mental Health & Social Care NHS Trust
city: Milton Keynes
country: United Kingdom
facility: Milton Keynes
city: Newport
country: United Kingdom
facility: Royal Gwent Hospital
city: Northumberland
country: United Kingdom
facility: North Tyneside General Hospital
city: Norwich
country: United Kingdom
facility: Norfolk and Norwich University Hospitals NHS Foundation Trust
city: Oxford
country: United Kingdom
facility: Oxford University Hospitals NHS Foundation Trust
city: Plymouth
country: United Kingdom
facility: Plymouth Hospitals NHS Trust
city: Poole
country: United Kingdom
facility: Poole Hospital NHS Trust
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
city: Surrey
country: United Kingdom
facility: Dr Dhakam
Study officials:
affiliation: Newcastle University
name: David J Burn, Professor
role: STUDY_CHAIR
affiliation: Cambridge University
name: Roger A Barker, Dr
role: STUDY_DIRECTOR
affiliation: lay person
name: Belinda Braithwaite, Mrs
role: STUDY_DIRECTOR
affiliation: School of Community Based Medicine, University of Manchester
name: Alistair Burns, Professor
role: STUDY_DIRECTOR
affiliation: Clarke
name: Carl E Clarke, Professor
role: STUDY_DIRECTOR
affiliation: University of Newcastle Upon-Tyne
name: Elaine McColl, Professor
role: STUDY_DIRECTOR
affiliation: Llandudno Hospital & University of College Wales
name: John V Hindle, Dr
role: STUDY_DIRECTOR
affiliation: London School of Economics and Political Science
name: Martin Knapp, Professor
role: STUDY_DIRECTOR
affiliation: University College, London
name: Andrew J Lees, Professor
role: STUDY_DIRECTOR
affiliation: Lancashire Care Trust, Royal Blackburn Hospital
name: Iracema Leroi, DR
role: STUDY_DIRECTOR
affiliation: Newcastle University
name: Ian G McKeith, Professor
role: STUDY_DIRECTOR
affiliation: Newcastle University
name: John T O'Brien, Professor
role: STUDY_DIRECTOR
affiliation: Cancer Research UK Clinical Trials Unit, School of Cancer Sciences, University of Birmingham
name: Keith Wheatley, Professor
role: STUDY_DIRECTOR
affiliation: University of Newcastle Upon-Tyne
name: Ian N Steen, Dr
role: STUDY_DIRECTOR
affiliation: University of Newcastle Upon-Tyne
name: Jennifer Wilkinson, Mrs
role: STUDY_DIRECTOR
affiliation: University of Newcastle Upon-Tyne
name: Sharon Erb, Mrs
role: STUDY_DIRECTOR
affiliation: Associate Professor of Psychiatry and Neurology, Perelman School of Medicine at the University of Pennsylvania
name: Daniel Weintraub
role: STUDY_DIRECTOR
affiliation: Professor of Human Movement Science, Institute for Ageing and Health, Newcastle University
name: Lynn Rochester
role: STUDY_DIRECTOR
References: