Donepezil and memantine in moderate to severe Alzheimer's disease

ISRCTN	ISRCTN49545035
DOI	https://doi.org/10.1186/ISRCTN49545035
ClinicalTrials.gov (NCT)	NCT00866060
Clinical Trials Information System (CTIS)	2007-001172-36
Protocol serial number	2006/123
Sponsor	Institute of Psychiatry (UK)
Funder	Medical Research Council (UK) (grant ref: G0600989)

Submission date: 28/03/2007
Registration date: 04/04/2007
Last edited: 05/12/2017

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Nervous System Diseases

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

http://www.ctu.mrc.ac.uk/research_areas/study_details.aspx?s=50

Contact information

Prof Robert Howard
Scientific

Old Age Psychiatry, PO70
Institute of Psychiatry
De Crespigny Park
London
SE5 8AF
United Kingdom

Study information

Primary study design	Interventional
Study design	Pragmatic multi-centre double-blind randomised placebo-controlled (double-dummy) parallel group 2 x 2 factorial clinical trial
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
Scientific title	DOnepezil and Memantine IN mOderate to severe Alzheimer's Disease
Study acronym	DOMINO - AD
Study objectives	The trial will test a number of hypotheses in patients who have declined in terms of cognitive function to reach the transition point to moderate-to-severe Alzheimer's Disease (AD): 1. Patients with AD who continue donepezil beyond the moderate to severe transition point will show a significantly smaller decline on ratings of cognitive function and activities of daily living over the following 12 months than those discontinuing donepezil 2. Patients with AD who commence memantine therapy will show a significantly smaller decline on ratings of cognitive function and activities of daily living over the following 12 months than those who do not 3. Patients given the combination of memantine and donepezil will show additive or synergistic significant benefits on measures of activities of daily living and cognitive function after 12 months compared to those patients continuing on either monotherapy 4. Treatment of patients with donepezil beyond the moderate to severe transition point will be more cost-effective than discontinuing donepezil. Memantine therapy will be more cost-effective than placebo. The combination of memantine and donepezil will be more cost-effective than monotherapy.
Ethics approval(s)	Scotland A Research Ethics Committee on 28/05/2007 (ref: 07/MRE00/52).
Health condition(s) or problem(s) studied	Alzheimer's Disease
Intervention	There will be four arms being assessed (all patients will be on donepezil when entering the trial): Arm one: combination of donepezil 10 mg plus memantine 20 mg Arm two: withdrawal of donepezil and prescription of memantine 20 mg Arm three: continued prescription of donepezil 10 mg Arm four: withdrawal of donepezil The patients on each arm will receive the appropriate treatment once daily for 52 weeks.
Intervention type	Drug
Phase	Not Specified
Drug / device / biological / vaccine name(s)	Donepezil, memantine
Primary outcome measure(s)	1. Cognitive function measured by the Standardised Mini Mental State Exam (SMMSE) 2. Activities of daily living measured using the Bristol Activities of Daily Living Scale (BADLS) All measures will be taken at zero, six, 18, 30 and 52 weeks.
Key secondary outcome measure(s)	1. Non-cognitive dementia symptoms measured using the neuropsychiatric inventory 2. Health related quality of life measured by Euro Quality of Life (EQ-5D) questionnaire and Demential Quality of Life (DEMQOL)-proxy 3. Care giver burden measured by the 12-item General Health Questionnaire (GHQ-12) 4. Cost effectiveness measured using the client service receipt inventory in conjunction with SMMSE and BADLS results All measures will be taken at zero, six, 18, 30 and 52 weeks.
Completion date	31/08/2013

Eligibility

Participant type(s)	Patient
Age group	Not Specified
Sex	Not Specified
Target sample size at registration	800
Key inclusion criteria	Participants will be patients who meet National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS/ADRDA) criteria for probable or possible AD and in addition will meet all of the following criteria: 1. Continuously prescribed donepezil for at least three months 2. No change in dosage of donepezil in previous six weeks 3. No changes in prescription of any psychotropic (antipsychotic, antidepressant, benzodiazepine) medication in previous four weeks 4. Prescribing clinician considers (based on National Institute of Clinical Excellence [NICE] guidance, discussions with patient and carer and clinical judgement) that change of drug treatment (i.e. stop donepezil or introduce memantine) may be appropriate and Standardised Mini Mental State Exam (SMMSE) = 5 to 13 (13 chosen as NICE threshold of 10 plus 1 SD on SMMSE score) 5. Patient is community resident and has family or professional carer or is visited on at least a daily basis by carer 6. Patient agrees to participate where possible 7. Main carer (informal or institutional) consents to their own involvement
Key exclusion criteria	1. Patient has severe, unstable or poorly controlled medical conditions apparent from physical examination or clinical history 2. Patient is already prescribed memantine 3. Patient is unable to take trial medications 4. Patient is involved in another clinical trial 5. Patient has absolute contraindication to either donepezil or memantine 6. Clinician considers patient would not be compliant with medication
Date of first enrolment	01/11/2007
Date of final enrolment	31/08/2013

Locations

Countries of recruitment

United Kingdom
England

Study participating centre

Old Age Psychiatry, PO70

London
SE5 8AF
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	08/03/2012		Yes	No
Protocol article	protocol	24/07/2009		Yes	No
Other publications	secondary analysis	01/12/2015		Yes	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes
Study website	Study website	11/11/2025	11/11/2025	No	Yes

Editorial Notes

05/12/2017: internal review.
02/11/2015: Publication reference added.