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DOnepezil and Memantine IN mOderate to severe Alzheimer's Disease
ISRCTN ISRCTN49545035
DOI 10.1186/ISRCTN49545035
ClinicalTrials.gov identifier NCT00866060
EudraCT number 2007-001172-36
Public title DOnepezil and Memantine IN mOderate to severe Alzheimer's Disease
Scientific title
Acronym DOMINO - AD
Serial number at source 2006/123
Study hypothesis 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.
Lay summary http://www.ctu.mrc.ac.uk/research_areas/study_details.aspx?s=50
Ethics approval Scotland A Research Ethics Committee on 28/05/2007 (ref: 07/MRE00/52).
Study design Pragmatic multi-centre double-blind randomised placebo-controlled (double-dummy) parallel group 2 x 2 factorial clinical trial
Countries of recruitment United Kingdom
Disease/condition/study domain Alzheimer's Disease
Participants - 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
Participants - 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
Anticipated start date 01/11/2007
Anticipated end date 31/08/2013
Status of trial Completed
Patient information material Patient information can be found at: http://neuroscience.iop.kcl.ac.uk/domino/docs/patient.pdf
Target number of participants 800
Interventions 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.
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.
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.
Sources of funding Medical Research Council (UK) (grant ref: G0600989)
Trial website http://neuroscience.iop.kcl.ac.uk/domino/default.aspx
Publications 1. 2009 protocol in http://www.ncbi.nlm.nih.gov/pubmed/19630974
2. 2012 results in http://www.ncbi.nlm.nih.gov/pubmed/22397651
Contact name Prof  Robert  Howard
  Address Old Age Psychiatry, PO70
Institute of Psychiatry
De Crespigny Park
  City/town London
  Zip/Postcode SE5 8AF
  Country United Kingdom
Sponsor Institute of Psychiatry (UK)
  Address c/o Gill Dale
Research and Development Office
Kings College London
De Crespigny Park
  City/town London
  Zip/Postcode SE5 8AF
  Country United Kingdom
  Sponsor website: http://www.iop.kcl.ac.uk/
Date applied 28/03/2007
Last edited 05/04/2012
Date ISRCTN assigned 04/04/2007
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