Donepezil and Memantine in Moderate to Severe Alzheimer's Disease
Information source: King's College London
Information obtained from ClinicalTrials.gov on February 07, 2013
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Moderate to Severe Alzheimer's Disease
Intervention: Memantine (Drug); Donepezil (Drug); Placebo donepezil (Drug); Placebo memantine (Drug)
Phase: Phase 4
Sponsored by: King's College London
Official(s) and/or principal investigator(s):
Robert J Howard, MD, Principal Investigator, Affiliation: Institute of Psychiatry
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.
1. 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.
2. 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.
3. 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.
Official title: Donepezil and Memantine in Moderate to Severe Alzheimer's Disease
Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Factorial Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Cognitive Function measured with the Standardised MMSE (SMMSE).
Activities of Daily Living measured with the Bristol Activities of Daily Living scale (BADLS).
Non−cognitive dementia symptoms measured with the Neuropsychiatric Inventory (NPI) and the Cohen−Mansfield Agitation Inventory.
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.
Care−giver burden measured with the General Health Questionnaire.
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).
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.
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.
Minimum age: N/A.
Maximum age: N/A.
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
1. SMMSE = 5 to 13 (13 chosen as NICE threshold of 10 plus 1 SD on SMMSE score)
2. Continuously prescribed donepezil for at least 3 months
3. Maintained on 10mg donepezil in previous 6 weeks.
4. No changes in prescription of any psychotropic (antipsychotic, antidepressant,
benzodiazepine) medication in previous 6 weeks.
5. 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.
6. Patient is community resident and has family or professional carer or is visited on
at least a daily basis by carer.
7. Patient agrees to participate if considered capable (see section 7. 5)
8. Main carer (informal or professional) consents to their own involvement and the
patient's involvement -
To maximise the generalisability of the study data, exclusions will be kept to a minimum.
These will include:
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 because of contra-indications or previous
adverse or allergic reactions.
4. Patient is involved in another clinical trial.
5. Clinician considers patient would not be compliant with trial medication. -
Locations and Contacts
Institute of Psychiatry, London SE5 8AF, United Kingdom; Recruiting
Robert J Howard, MD, Phone: 020 7848 0545, Email: firstname.lastname@example.org
Robert J Howard, MD, Principal Investigator
Starting date: February 2008
Last updated: March 19, 2009