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

NCT01014858 | Terminated Phase 3 DMC

• 2 other identifiers: 513708/13/14
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 22

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.

Conditions

Parkinson's Disease

Keywords

Parkinson's disease; mild dementia; donepezil; NIHR HTA

Outcome Measures

Primary Outcomes (1)

• 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 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.

  26, 52 and 104 weeks

Study Arms (2)

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.

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.

Drug: Donepezil

Interventions

Donepezil DRUG

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

Donepezil; Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

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

Study Sites (22)

Newcastle

Newcastle upon Tyne, Tyne and Wear, NE4 5PL, United Kingdom

Location

Royal United Hospital (RUH) Bath NHS

Bath, BA1 3NG, United Kingdom

Location

Sandwell and West Birmingham NHS Foundation Trust

Birmingham, B18 7QH, United Kingdom

Location

Steps and Pines, Southmead Hospital

Bristol, BS10 5NB, United Kingdom

Location

Pennine Acute Hospitals NHS Trust

Bury, BL9 7TD, United Kingdom

Location

Cambridge Centre for Brain Repair

Cambridge, CB2 0PY, United Kingdom

Location

Dr Lakmali Sugathapala

Derby, DE22 3NE, United Kingdom

Location

Royal Bournemouth & Christchurch Hospitals NHS Foundation Trust

Dorset, BH23 2JX, United Kingdom

Location

NHS Greater Glasgow and Clyde

Glasgow, G51 4TF, United Kingdom

Location

Dr Pippa Metcalf

Gloucester, Gloucester, United Kingdom

Location

Llandudno Hospital, Betsi Cadwaladr University Health Board & School of Medical Sciences

Llandudno, LL30 1LB, United Kingdom

Location

King's College Hospital NHS Foundtion Trust

London, SE59RS, United Kingdom

Location

Manchester Mental Health & Social Care NHS Trust

Manchester, M8 5RB, United Kingdom

Location

Milton Keynes

Milton Keynes, MK6 5LD, United Kingdom

Location

Royal Gwent Hospital

Newport, NP20 2UB, United Kingdom

Location

North Tyneside General Hospital

Northumberland, NE29 8NH, United Kingdom

Location

Norfolk and Norwich University Hospitals NHS Foundation Trust

Norwich, NR4 7UY, United Kingdom

Location

Oxford University Hospitals NHS Foundation Trust

Oxford, OX3 9DU, United Kingdom

Location

Plymouth Hospitals NHS Trust

Plymouth, PL6 8DH, United Kingdom

Location

Poole Hospital NHS Trust

Poole, BH15 2JB, United Kingdom

Location

Southampton General Hospital

Southampton, SO16 6YD, United Kingdom

Location

Dr Dhakam

Surrey, KT16 0PZ, United Kingdom

Location

MeSH Terms

Conditions

Parkinson Disease

Interventions

Donepezil

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Intervention Hierarchy (Ancestors)

Indans; Indenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Polycyclic Compounds

Study Officials

• David J Burn, Professor

  Newcastle University

  STUDY CHAIR

• Roger A Barker, Dr

  Cambridge University

  STUDY DIRECTOR

• Belinda Braithwaite, Mrs

  lay person

  STUDY DIRECTOR

• Alistair Burns, Professor

  School of Community Based Medicine, University of Manchester

  STUDY DIRECTOR

• Carl E Clarke, Professor

  Clarke

  STUDY DIRECTOR

• Elaine McColl, Professor

  University of Newcastle Upon-Tyne

  STUDY DIRECTOR

• John V Hindle, Dr

  Llandudno Hospital & University of College Wales

  STUDY DIRECTOR

• Martin Knapp, Professor

  London School of Economics and Political Science

  STUDY DIRECTOR

• Andrew J Lees, Professor

  University College, London

  STUDY DIRECTOR

• Iracema Leroi, DR

  Lancashire Care Trust, Royal Blackburn Hospital

  STUDY DIRECTOR

• Ian G McKeith, Professor

  Newcastle University

  STUDY DIRECTOR

• John T O'Brien, Professor

  Newcastle University

  STUDY DIRECTOR

• Keith Wheatley, Professor

  Cancer Research UK Clinical Trials Unit, School of Cancer Sciences, University of Birmingham

  STUDY DIRECTOR

• Ian N Steen, Dr

  University of Newcastle Upon-Tyne

  STUDY DIRECTOR

• Jennifer Wilkinson, Mrs

  University of Newcastle Upon-Tyne

  STUDY DIRECTOR

• Sharon Erb, Mrs

  University of Newcastle Upon-Tyne

  STUDY DIRECTOR

• Daniel Weintraub

  Associate Professor of Psychiatry and Neurology, Perelman School of Medicine at the University of Pennsylvania

  STUDY DIRECTOR

• Lynn Rochester

  Professor of Human Movement Science, Institute for Ageing and Health, Newcastle University

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 16, 2009
• First Posted: November 17, 2009
• Study Start: January 1, 2013
• Primary Completion: September 1, 2014
• Study Completion: September 1, 2014
• Last Updated: September 25, 2017

Record last verified: 2017-09

Locations

GB (22)