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

This study is currently recruiting participants.
Verified March 2013 by Newcastle-upon-Tyne Hospitals NHS Trust
Sponsor:
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 Trust
Newcastle University
King's College London
Information provided by (Responsible Party):
Sharon Erb, Newcastle-upon-Tyne Hospitals NHS Trust
ClinicalTrials.gov Identifier:
NCT01014858
First received: November 16, 2009
Last updated: March 27, 2013
Last verified: March 2013
  Purpose

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.


Condition Intervention Phase
Parkinson's Disease
Drug: Donepezil
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Multi-centre UK Study of the Acetylcholinesterase Inhibitor Donepezil in Early Dementia Associated With Parkinson's Disease

Resource links provided by NLM:


Further study details as provided by Newcastle-upon-Tyne Hospitals NHS Trust:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Estimated Enrollment: 500
Study Start Date: January 2013
Estimated Study Completion Date: May 2017
Estimated Primary Completion Date: May 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Donepezil
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
5mg donepezil daily for first 8 weeks and then increased to 10mg daily for the remainder of the study.
Placebo Comparator: Placebo
Patient commences medication to match appearance of 5mg donepezil for first 8 weeks then 10mg for the remainder of the study.
Drug: Donepezil
5mg donepezil daily for first 8 weeks and then increased to 10mg daily for the remainder of the study.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01014858

Contacts
Contact: David J Burn, Professor +44 (0)191 2481266 d.j.burn@ncl.ac.uk
Contact: Sharon Erb, Mrs +44 (0)191 222 5364 sharon.erb@ncl.ac.uk

Locations
United Kingdom
Newcastle Recruiting
Newcastle Upon Tyne, Tyne and Wear, United Kingdom, NE4 5PL
Principal Investigator: David Burn         
Dr Nin Bajaj Not yet recruiting
Derby, United Kingdom, DE22 3NE
Principal Investigator: Nin Bajaj         
Dr Pippa Metcalf Not yet recruiting
Gloucester, United Kingdom, Gloucester
Principal Investigator: Pippa Metcalf         
Milton Keynes Not yet recruiting
Milton Keynes, United Kingdom, MK6 5LD
Principal Investigator: Michele Hu         
Dr Dhakam Not yet recruiting
Surrey, United Kingdom, KT16 0PZ
Principal Investigator: Zahid Dhakam         
Sponsors and Collaborators
Sharon Erb
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 Trust
Newcastle University
King's College London
Investigators
Study Chair: David J Burn, Professor Newcastle University
Study Director: 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
  More Information

No publications provided

Responsible Party: Sharon Erb, Trial Manager, Newcastle-upon-Tyne Hospitals NHS Trust
ClinicalTrials.gov Identifier: NCT01014858     History of Changes
Other Study ID Numbers: 5137, 08/13/14
Study First Received: November 16, 2009
Last Updated: March 27, 2013
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Newcastle-upon-Tyne Hospitals NHS Trust:
Parkinson's disease
mild dementia
donepezil
NIHR HTA

Additional relevant MeSH terms:
Dementia
Parkinson Disease
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Parkinsonian Disorders
Basal Ganglia Diseases
Movement Disorders
Neurodegenerative Diseases
Cholinesterase Inhibitors
Donepezil
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Cholinergic Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Nootropic Agents
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 17, 2014