Moderate to Severe Alzheimer's DiseasePhase 4DOMINO-ADNCT00866060
Donepezil and Memantine in Moderate to Severe Alzheimer's Disease
A Phase 4 study testing Memantine and Donepezil in people with Moderate to Severe Alzheimer's Disease, run by King's College London at 1 site in United Kingdom.
Trial summary
The trial will examine whether pharmacological treatment with donepezil, memantine or combination of memantine and donepezil is any better than a placebo (dummy) treatment in people with Alzheimer's disease who have reached the moderate to severe stage of illness. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Moderate to Severe Alzheimer's Disease
- What is being tested?
- Memantine and Donepezil
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 800 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Feb 2008to Jun 2013
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Participants will be patients who meet NINCDS-ADRDA criteria for probable or possible Alzheimer's disease (McKhann et al, 1984). In addition they will meet all of the following criteria:
- SMMSE = 5 to 13 (13 chosen as NICE threshold of 10 plus 1 SD on SMMSE score)
- Continuously prescribed donepezil for at least 3 months
- Maintained on 10mg donepezil in previous 6 weeks.
- No changes in prescription of any psychotropic (antipsychotic, antidepressant, benzodiazepine) medication in previous 6 weeks.
- Prescribing clinician considers (based on 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.
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- Patient is community resident and has family or professional carer or is visited on at least a daily basis by carer.
- Patient agrees to participate if considered capable (see section 7.5)
- Main carer (informal or professional) consents to their own involvement and the patient's involvement -
Who cannot join
- To maximise the generalisability of the study data, exclusions will be kept to a minimum. These will include:
- Patient has severe, unstable or poorly controlled medical conditions apparent from physical examination or clinical history.
- Patient is already prescribed memantine.
- Patient is unable to take trial medications because of contra-indications or previous adverse or allergic reactions.
- Patient is involved in another clinical trial.
- Clinician considers patient would not be compliant with trial medication. -
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site, 1 recruiting
- Recruiting
Institute of Psychiatry
London, SE5 8AF
Robert J Howard, MD, 020 7848 0545, r.howard@iop.kcl.ac.uk
Robert J Howard, MD
About this study
The trial will examine whether pharmacological treatment with donepezil, memantine or combination of memantine and donepezil is any better than a placebo (dummy) treatment in people with Alzheimer's disease who have reached the moderate to severe stage of illness. Using a double blind design, where neither the investigators nor participants know who is receiving which treatment, participants will be randomly assigned to one of these four treatment groups (donepezil and memantine, memantine only, donepezil only or placebo). In order to keep both the investigators and participants blind to drug allocation a double dummy design will be necessary. This means that each participant will receive 2 treatments - either an active form or placebo of each of the 2 study drugs.
Hypotheses are:
- Patients with Alzheimer's disease (AD) who continue donepezil beyond the point of transition from moderate to severe dementia continue to show significantly less decline on ratings of cognitive function and activities of daily living over the following 12 months than those discontinuing donepezil.
- Patients with AD who change to memantine therapy in place of donepezil at the point of transition from moderate to severe dementia show significantly smaller decline on ratings of cognitive function and activities of daily living over the following 12 months than those who receive placebo.
- Patients given the combination of memantine and donepezil at the point of transition from moderate to severe dementia show significant additive or synergistic benefits on measures of activities of daily living and cognitive function after 12 months compared to those patients continuing on either drug as a single treatment.
Read the detailed description
This trial will involve the withdrawal of drug participants that are currently on (donepezil) and in arm 4, the participant will only be on placebo treatment. It is important to include this arm of the study as a key objective in looking at the benefit of continuing donepezil and therefore a placebo arm should be present as a comparator. To reduce the risk to participants of withdrawing donepezil too early in their illness, an inclusion criteria is that the participant is at a stage in their disease whereby the prescribing clinician feels a change in drug prescription may be appropriate.
- Conditions
- Moderate to Severe Alzheimer's Disease
- Being tested
- Memantine, Donepezil, Placebo donepezil, Placebo memantine
- Keywords
- donepezil, memantine, moderately severe Alzheimer's disease, severe Alzheimer's disease
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MemantineDrug
Also called Ebixa
20mg memantine
DonepezilDrug
Also called Aricept
10mg donepezil
Placebo donepezilDrug
Placebo donepezil
Placebo memantineDrug
Placebo memantine
| Study group | Role | What they receive |
|---|---|---|
| 1 | Active comparator | 10mg donepezil plus 20mg memantine
Participants in this arm will continue with their current donepezil 10mg/day regimen and immediately commence active memantine at a dose of 5mg per day, increasing in 5mg increments weekly until 20mg per day is achieved from week 4 onwards Receives: Drug: Memantine; Drug: Donepezil |
| 2 | Placebo comparator | Placebo donepezil plus 20mg memantine
Participants in this arm will immediately commence active memantine at a dose of 5mg per day, increasing in 5mg increments weekly until 20mg per day is achieved from week 4 onwards. Donepezil dose will be reduced to 5mg daily in weeks 1 to 4 and replaced with placebo donepezil in week 5. Receives: Drug: Memantine; Drug: Placebo donepezil |
| 3 | Placebo comparator | 10mg donepezil plus placebo memantine
Participants in this arm will continue with their current donepezil 10mg/day regimen and immediately commence placebo memantine. Receives: Drug: Donepezil; Drug: Placebo memantine |
| 4 | Placebo comparator | Placebo donepezil plus placebo memantine
Participants in this arm will immediately commence placebo memantine dose escalation and will switch to donepezil 5mg daily in weeks 1 to 4, and replaced with placebo donepezil in week 5. Receives: Drug: Placebo donepezil; Drug: Placebo memantine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cognitive Function measured with the Standardised MMSE (SMMSE).
Measured: 4 years
Activities of Daily Living measured with the Bristol Activities of Daily Living scale (BADLS).
Measured: 4 years
Secondary outcomes (5)
Non-cognitive dementia symptoms measured with the Neuropsychiatric Inventory (NPI) and the Cohen-Mansfield Agitation Inventory.
Measured: 4 years
Health-related quality of life measured with the EQ-5D (Euroqol Group 1990) and the DEMQOL-Proxy (Smith et al 2004) - a carer-rated and disease-specific measure of quality of life in dementia.
Measured: 4 years
Care-giver burden measured with the General Health Questionnaire.
Measured: 4 years
Cost effectiveness assessed through consideration of the combination of costs generated from the Client Service Receipt Inventory (CSRI) and the assessments of function and quality of life (BADLS, DEMQOL, EQ-5D).
Measured: 4 years
Institutionalisation defined as permanent transition from living in an independent household to a care home, NHS continuing care unit or hospital and measured with questions taken from the CSRI and telephone interviews.
Measured: 4 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Mar 2009 (estimated)
- Study startFeb 2008
- Primary completionFeb 2012 (estimated)
- Study completionJun 2013 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Moderate to Severe Alzheimer's DiseaseStudies of the same condition, open and under way.
- More trials run by King's College LondonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 800 participants (estimated)
Sponsor and investigators
- Lead sponsor
- King's College London
- Sponsor type
- University, hospital or other
- Investigators
- Robert J Howard, MD, Principal investigator, Institute of Psychiatry
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00866060
- Sponsor's protocol ID
- 2006/123
- Other IDs
- ISRCTN49545035, Eudract 2007-001172-36
- Acronym
- DOMINO-AD
- Status last verified
- Mar 2009
- First submitted
- 19 Mar 2009
- Last updated
- 20 Mar 2009
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 20 Mar 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Donepezil and Memantine in Moderate to Severe Alzheimer's Disease
- ClinicalTrials.gov ID
- NCT00866060
- Acronym / sponsor ID
- DOMINO-AD / 2006/123
- Conditions
- Moderate to Severe Alzheimer's Disease
- Keywords
- donepezil, memantine, moderately severe Alzheimer's disease, severe Alzheimer's disease
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 800 participants (estimated)
- Lead sponsor
- King's College LondonUniversity, hospital or other
- Study start
- Feb 2008
- Primary completion
- Feb 2012 (estimated)
- Study completion
- Jun 2013 (estimated)
- First posted
- 20 Mar 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The trial will examine whether pharmacological treatment with donepezil, memantine or combination of memantine and donepezil is any better than a placebo (dummy) treatment in people with Alzheimer's disease who have reached the moderate to severe stage of illness. Using a double blind design, where neither the investigators nor participants know who is receiving which treatment, participants will be randomly assigned to one of these four treatment groups (donepezil and memantine, memantine only, donepezil only or placebo). In order to keep both the investigators and participants blind to drug allocation a double dummy design will be necessary. This means that each participant will receive 2 treatments - either an active form or placebo of each of the 2 study drugs.
Hypotheses are:
- Patients with Alzheimer's disease (AD) who continue donepezil beyond the point of transition from moderate to severe dementia continue to show significantly less decline on ratings of cognitive function and activities of daily living over the following 12 months than those discontinuing donepezil.
- Patients with AD who change to memantine therapy in place of donepezil at the point of transition from moderate to severe dementia show significantly smaller decline on ratings of cognitive function and activities of daily living over the following 12 months than those who receive placebo.
- Patients given the combination of memantine and donepezil at the point of transition from moderate to severe dementia show significant additive or synergistic benefits on measures of activities of daily living and cognitive function after 12 months compared to those patients continuing on either drug as a single treatment.
Detailed description
This trial will involve the withdrawal of drug participants that are currently on (donepezil) and in arm 4, the participant will only be on placebo treatment. It is important to include this arm of the study as a key objective in looking at the benefit of continuing donepezil and therefore a placebo arm should be present as a comparator. To reduce the risk to participants of withdrawing donepezil too early in their illness, an inclusion criteria is that the participant is at a stage in their disease whereby the prescribing clinician feels a change in drug prescription may be appropriate.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 1 | Active comparator | Drug: Memantine, Drug: Donepezil10mg donepezil plus 20mg memantine Participants in this arm will continue with their current donepezil 10mg/day regimen and immediately commence active memantine at a dose of 5mg per day, increasing in 5mg increments weekly until 20mg per day is achieved from week 4 onwards |
| 2 | Placebo comparator | Drug: Memantine, Drug: Placebo donepezilPlacebo donepezil plus 20mg memantine Participants in this arm will immediately commence active memantine at a dose of 5mg per day, increasing in 5mg increments weekly until 20mg per day is achieved from week 4 onwards. Donepezil dose will be reduced to 5mg daily in weeks 1 to 4 and replaced with placebo donepezil in week 5. |
| 3 | Placebo comparator | Drug: Donepezil, Drug: Placebo memantine10mg donepezil plus placebo memantine Participants in this arm will continue with their current donepezil 10mg/day regimen and immediately commence placebo memantine. |
| 4 | Placebo comparator | Drug: Placebo donepezil, Drug: Placebo memantinePlacebo donepezil plus placebo memantine Participants in this arm will immediately commence placebo memantine dose escalation and will switch to donepezil 5mg daily in weeks 1 to 4, and replaced with placebo donepezil in week 5. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (9 listed)
- Participants will be patients who meet NINCDS-ADRDA criteria for probable or possible Alzheimer's disease (McKhann et al, 1984). In addition they will meet all of the following criteria:
- SMMSE = 5 to 13 (13 chosen as NICE threshold of 10 plus 1 SD on SMMSE score)
- Continuously prescribed donepezil for at least 3 months
- Maintained on 10mg donepezil in previous 6 weeks.
- No changes in prescription of any psychotropic (antipsychotic, antidepressant, benzodiazepine) medication in previous 6 weeks.
Key exclusion criteria (6 listed)
- To maximise the generalisability of the study data, exclusions will be kept to a minimum. These will include:
- Patient has severe, unstable or poorly controlled medical conditions apparent from physical examination or clinical history.
- Patient is already prescribed memantine.
- Patient is unable to take trial medications because of contra-indications or previous adverse or allergic reactions.
- Patient is involved in another clinical trial.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MemantineAlso: Ebixa20mg memantine | Drug | 1, 2 |
| DonepezilAlso: Aricept10mg donepezil | Drug | 1, 3 |
| Placebo donepezilPlacebo donepezil | Drug | 2, 4 |
| Placebo memantinePlacebo memantine | Drug | 3, 4 |
Primary outcome
Cognitive Function measured with the Standardised MMSE (SMMSE).
Time frame: 4 years
Activities of Daily Living measured with the Bristol Activities of Daily Living scale (BADLS).
Time frame: 4 years
5 secondary outcomes
Non-cognitive dementia symptoms measured with the Neuropsychiatric Inventory (NPI) and the Cohen-Mansfield Agitation Inventory.
Time frame: 4 years
Health-related quality of life measured with the EQ-5D (Euroqol Group 1990) and the DEMQOL-Proxy (Smith et al 2004) - a carer-rated and disease-specific measure of quality of life in dementia.
Time frame: 4 years
Care-giver burden measured with the General Health Questionnaire.
Time frame: 4 years
Cost effectiveness assessed through consideration of the combination of costs generated from the Client Service Receipt Inventory (CSRI) and the assessments of function and quality of life (BADLS, DEMQOL, EQ-5D).
Time frame: 4 years
Institutionalisation defined as permanent transition from living in an independent household to a care home, NHS continuing care unit or hospital and measured with questions taken from the CSRI and telephone interviews.
Time frame: 4 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Mar 2009.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Robert J Howard, MD principal investigator
Institute of Psychiatry
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Memantine and Donepezil in people with Moderate to Severe Alzheimer's Disease, run by King's College London at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 20 Mar 2009. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cognitive Function measured with the Standardised MMSE (SMMSE). (time frame: 4 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Mar 2009.