Donepezil and memantine in moderate to severe Alzheimer's disease
| ISRCTN | ISRCTN49545035 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN49545035 |
| EudraCT/CTIS number | 2007-001172-36 |
| ClinicalTrials.gov number | NCT00866060 |
| Secondary identifying numbers | 2006/123 |
- 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
http://www.ctu.mrc.ac.uk/research_areas/study_details.aspx?s=50
Contact information
Prof Robert Howard
Scientific
Scientific
Old Age Psychiatry, PO70
Institute of Psychiatry
De Crespigny Park
London
SE5 8AF
United Kingdom
Study information
| Study design | Pragmatic multi-centre double-blind randomised placebo-controlled (double-dummy) parallel group 2 x 2 factorial clinical trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Not specified |
| Study type | Treatment |
| Participant information sheet | Patient information can be found at: http://neuroscience.iop.kcl.ac.uk/domino/docs/patient.pdf |
| Scientific title | DOnepezil and Memantine IN mOderate to severe Alzheimer's Disease |
| Study acronym | DOMINO - AD |
| 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. |
| Ethics approval(s) | Scotland A Research Ethics Committee on 28/05/2007 (ref: 07/MRE00/52). |
| Condition | 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 |
| Pharmaceutical study type(s) | |
| Phase | Not Specified |
| Drug / device / biological / vaccine name(s) | Donepezil, memantine |
| Primary outcome measure | 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 measures | 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. |
| Overall study start date | 01/11/2007 |
| Overall study end date | 31/08/2013 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Not Specified |
| Sex | Not Specified |
| Target number of participants | 800 |
| Participant 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 |
| Participant 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 |
| Recruitment start date | 01/11/2007 |
| Recruitment end date | 31/08/2013 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
Old Age Psychiatry, PO70
London
SE5 8AF
United Kingdom
SE5 8AF
United Kingdom
Sponsor information
Institute of Psychiatry (UK)
Research organisation
Research organisation
c/o Gill Dale
Research and Development Office
Kings College London
De Crespigny Park
London
SE5 8AF
United Kingdom
| Website | http://www.iop.kcl.ac.uk/ |
|---|---|
"ROR" |
https://ror.org/0220mzb33 |
Funders
Funder type
Research council
Medical Research Council (UK) (grant ref: G0600989)
Government organisation / National government
Government organisation / National government
- Alternative name(s)
- Medical Research Council (United Kingdom), UK Medical Research Council, MRC
- Location
- United Kingdom
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol article | protocol | 24/07/2009 | Yes | No | |
| Results article | results | 08/03/2012 | Yes | No | |
| Other publications | secondary analysis | 01/12/2015 | Yes | No |
Editorial Notes
05/12/2017: internal review.
02/11/2015: Publication reference added.
