Alzheimer's DiseasePhase 3NCT00857649
Efficacy and Safety of Memantine in Moderate to Severe Alzheimer's Disease
A Phase 3 study testing Memantine in people with Alzheimer's Disease, run by H. Lundbeck A/S at 23 sites in Canada.
Trial summary
The primary objective of this study is to examine the efficacy of memantine on cognition and behavioural symptoms in outpatients with moderate to severe dementia of the Alzheimer's type. Read more about this study
- Who is it for?
- Ages 50 years and older
- Conditions the study is for
- Alzheimer's Disease
- What is being tested?
- Memantine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 369 participants
- Where
- 23 sitesCanada
- Study dates
- Dec 2003to Sep 2010
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 50 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Outpatients who:
- had a primary diagnosis of probable Alzheimer's Disease (AD) according to National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINDS-ADRDA) criteria, and with Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revised (DSM IV TR) criteria for dementia of the Alzheimer's type
- had moderate to severe dementia, defined as a Mini Mental State Examination (MMSE) total score >=5 and <=15 at screening. Before substantial protocol amendment SA04 (dated 7 October 2004) was implemented, the MMSE total score range at screening was >=8 and <=18. Substantial protocol amendment SA07 (dated 4 September 2009) allowed patients who had previously had an MMSE score of 16 or 17 to be re-screened >6 months after their initial screening and, if there was documented evidence of cognitive decline, to be enrolled in the study
- had a Neuropsychiatric Inventory (NPI) total score >=13 and an NPI agitation/aggression subitem score >=1 at screening and baseline
- did not have vascular dementia or a modified Hachinski Ischaemia Scale score >4 at screening
Who cannot join
- Evidence of clinically significant active disease, evidence of other neurological disorders, and previous treatment with memantine
Trial locations and contacts
23 sites in 1 country.
23 sites in 1 country
Canada23 sites
CA005
Beauport, Quebec, G1J 2G3
CA032
Burlington, Ontario, L7M 4Y1
CA019
Edmonton, Alberta, T5G 0B7
CA023
Greenfield Park, Quebec, J4V 2J2
CA033
Kelowna, British Columbia, V1W 4V5
CA043
Kelowna, V1Y 3G8
CA046
Kentville, Nova Scotia, B4N 4K9
CA013
Montreal, Quebec, H1T 2M4
CA029
Orangeville, Ontario, L9W 2E1
CA004
Ottawa, Ontario, K1N 5C8
CA042
Penticton, V2A 5C8
CA038
Peterborough, Ontario, K9H 2P4
CA045
Pictou, Nova Scotia, B0K 1H0
CA015
Regina, Saskatchewan, S4T 1A5
CA022
Saint John, New Brunswick
CA040
Saskatoon, Saskatchewan, S7N 0W8
CA031
Sherbrooke, Quebec, J1J 2B8
CA012
Sherbrooke, Quebec, J1J 3H5
CA009
Toronto, Ontario, M3B 2W7
CA030
Vanier, Quebec, G1M 2R9
CA017
Verdun, Quebec, H4H 1R3
CA037
Windsor, Ontario, N8X 5A6
CA034
Winnipeg, Manitoba, R3M 0X9
About this study
Official title: A Randomised, Double-Blind, Parallel-Group Study Examining the Efficacy and Safety of Memantine in Patients With Moderate to Severe Dementia of the Alzheimer's Type
The primary objective of this study is to examine the efficacy of memantine on cognition and behavioural symptoms in outpatients with moderate to severe dementia of the Alzheimer's type.
Read the detailed description
Memantine is a moderate affinity, uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist. Pre-clinical studies have demonstrated that memantine can decrease the neuronal toxicity associated with excessive glutamate release and calcium overload in neurons. Results from clinical trials in patients with moderate to severe Alzheimer's Disease (AD) have demonstrated memantine's efficacy and safety by showing positive treatment effects on cognitive, global and functional decline.
This 24-week randomised, double-blind, placebo-controlled, multicentre study examines the effect of memantine 20 mg, administered once daily, on cognitive and behavioural symptoms in outpatients diagnosed with moderate to severe AD and significant psychopathology.
- Conditions
- Alzheimer's Disease
- Being tested
- Memantine, Placebo
- Keywords
- 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®
20 mg Oral Tablets Once Daily
PlaceboDrug
Oral Tablets Once Daily
| Study group | Role | What they receive |
|---|---|---|
| Memantine | Experimental | Not described Receives: Drug: Memantine |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Efficacy of Memantine on Behavioural Symptoms in Outpatients With Moderate to Severe Dementia of the Alzheimer's Type Using the NPI - 12 Items Version Total Score.
Change from Baseline in Neuropsychiatric Inventory (NPI) total score.
NPI is a validated scale that assesses behavioural disturbances in patients with dementia. The 12 item version consists of 10 behavioural and 2 neurovegetative areas. It provides both a total score as well as scores for a number of sub-scales. The frequency, severity and caregiver distress for each domain are measured. The NPI is based upon responses obtained from the caregiver. The total score is from 0 to 144. A higher score reflects more frequency and severity of the disturbances.
Measured: Baseline to Week 24
Efficacy of Memantine on Cognition in Outpatients With Moderate to Severe Dementia of the Alzheimer's Type Using the SIB Total Score.
Change from Baseline in Severe Impairment Battery (SIB) total score.
SIB is a validated scale used to assess cognitive function in patients with moderate to severe dementia. Items are single words or one-step commands combined with gestures. Nine domains are assessed, and the total score is between 0 and 100. A lower total score reflects the loss of cognitive function.
Measured: Baseline to Week 24
Secondary outcomes (3)
Efficacy of Memantine on Global Condition Using CIBIC-plus.
Clinician's Interview-Based Impression of Change-Plus Version (CIBIC-plus). Improvement evaluated with reference to Baseline.
CIBIC-plus is a global rating that is derived through an independent, comprehensive interview with the patient and caregiver by a rater who is barred from knowledge of all other psychometric test scores conducted as part of this protocol as well as from reported safety data. The rating is made on a 7-point scale ranging from "1 = marked improvement" to "7 = marked worsening". A score of "4" indicates no change.
Measured: Baseline to Week 24
Efficacy of Memantine on Functioning Using ADCS-ADL - 19 Items Total Score.
Change from Baseline on the Alzheimer's Disease Cooperative Study - Activities of Daily Living Inventory (ADCS-ADL) 19-item version total score.
ADCS-ADL- 19 items version for moderate to severe AD will measure patient's functioning. This battery of ADL questions is used here to measure the functional capabilities of patients with dementia. The inventory is done by interviewing a person in close contact with the patient and covers the most usual and consistent performance of the patient over the preceding 4 weeks. Total score is from 0 to 54. The higher score, the lower impairment.
Measured: Baseline to Week 24
Efficacy of Memantine on Functioning Using CMAI - Long Form Total Score.
Change from Baseline on the Cohen-Mansfield Agitation Inventory (CMAI) - Long Form total score.
CMAI - Long Form looks specifically at agitated behaviour in patients with cognitive impairment. It is a seven-point rating scale assessing the frequency of up to 29 agitated behaviours, ranging from "1 = Never" to "7 = Several times an hour". Rating is based on responses obtained from interviews with the caregiver. The total score ranges from 29 to 203, with a higher score reflecting more frequent behavioural disturbances.
Measured: Baseline to Week 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Mar 2009 (estimated)
- Study startDec 2003
- Primary completionApr 2010
- Study completionSep 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Alzheimer's DiseaseStudies of the same condition, open and under way.
- More trials run by H. Lundbeck A/SThe 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 369 participants (actual)
Sponsor and investigators
- Lead sponsor
- H. Lundbeck A/S
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Email contact via H. Lundbeck A/S, Study director, LundbeckClinicalTrials@lundbeck.com
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00857649
- Sponsor's protocol ID
- 10158
- Status last verified
- Nov 2013
- First submitted
- 5 Mar 2009
- Last updated
- 5 Dec 2013
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Herrmann N, Gauthier S, Boneva N, Lemming OM; 10158 Investigators. A randomized, double-blind, placebo-controlled trial of memantine in a behaviorally enriched sample of patients with moderate-to-severe Alzheimer's disease. Int Psychogeriatr. 2013 Jun;25(6):919-27. doi: 10.1017/S1041610213000239. Epub 2013 Mar 8.
PubMed 23472619
Study at a glance
From the registry record, last updated by the sponsor on 5 Dec 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised, Double-Blind, Parallel-Group Study Examining the Efficacy and Safety of Memantine in Patients With Moderate to Severe Dementia of the Alzheimer's Type
- ClinicalTrials.gov ID
- NCT00857649
- Acronym / sponsor ID
- 10158
- Conditions
- Alzheimer's Disease
- Keywords
- Alzheimer's Disease
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 369 participants (actual)
- Lead sponsor
- H. Lundbeck A/SIndustry (pharma, biotech, devices)
- Study start
- Dec 2003
- Primary completion
- Apr 2010 (actual)
- Study completion
- Sep 2010 (actual)
- First posted
- 6 Mar 2009 (estimated)
- Results
- Posted 9 Jan 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary objective of this study is to examine the efficacy of memantine on cognition and behavioural symptoms in outpatients with moderate to severe dementia of the Alzheimer's type.
Detailed description
Memantine is a moderate affinity, uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist. Pre-clinical studies have demonstrated that memantine can decrease the neuronal toxicity associated with excessive glutamate release and calcium overload in neurons. Results from clinical trials in patients with moderate to severe Alzheimer's Disease (AD) have demonstrated memantine's efficacy and safety by showing positive treatment effects on cognitive, global and functional decline.
This 24-week randomised, double-blind, placebo-controlled, multicentre study examines the effect of memantine 20 mg, administered once daily, on cognitive and behavioural symptoms in outpatients diagnosed with moderate to severe AD and significant psychopathology.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Memantine | Experimental | Drug: Memantine |
| Placebo | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 50 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- had a primary diagnosis of probable Alzheimer's Disease (AD) according to National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINDS-ADRDA) criteria, and with Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revised (DSM IV TR) criteria for dementia of the Alzheimer's type
- had moderate to severe dementia, defined as a Mini Mental State Examination (MMSE) total score >=5 and <=15 at screening. Before substantial protocol amendment SA04 (dated 7 October 2004) was implemented, the MMSE total score range at screening was >=8 and <=18. Substantial protocol amendment SA07 (dated 4 September 2009) allowed patients who had previously had an MMSE score of 16 or 17 to be re-screened >6 months after their initial screening and, if there was documented evidence of cognitive decline, to be enrolled in the study
- had a Neuropsychiatric Inventory (NPI) total score >=13 and an NPI agitation/aggression subitem score >=1 at screening and baseline
- did not have vascular dementia or a modified Hachinski Ischaemia Scale score >4 at screening
Key exclusion criteria (1 listed)
- Evidence of clinically significant active disease, evidence of other neurological disorders, and previous treatment with memantine
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: Ebixa®20 mg Oral Tablets Once Daily | Drug | Memantine |
| PlaceboOral Tablets Once Daily | Drug | Placebo |
Primary outcome
Efficacy of Memantine on Behavioural Symptoms in Outpatients With Moderate to Severe Dementia of the Alzheimer's Type Using the NPI - 12 Items Version Total Score.
Time frame: Baseline to Week 24
Change from Baseline in Neuropsychiatric Inventory (NPI) total score. NPI is a validated scale that assesses behavioural disturbances in patients with dementia. The 12 item version consists of 10 behavioural and 2 neurovegetative areas. It provides both a total score as well as scores for a number of sub-scales. The frequency, severity and caregiver distress for each domain are measured. The NPI is based upon responses obtained from the caregiver. The total score is from 0 to 144. A higher score reflects more frequency and severity of the disturbances.
Efficacy of Memantine on Cognition in Outpatients With Moderate to Severe Dementia of the Alzheimer's Type Using the SIB Total Score.
Time frame: Baseline to Week 24
Change from Baseline in Severe Impairment Battery (SIB) total score. SIB is a validated scale used to assess cognitive function in patients with moderate to severe dementia. Items are single words or one-step commands combined with gestures. Nine domains are assessed, and the total score is between 0 and 100. A lower total score reflects the loss of cognitive function.
3 secondary outcomes
Efficacy of Memantine on Global Condition Using CIBIC-plus.
Time frame: Baseline to Week 24
Efficacy of Memantine on Functioning Using ADCS-ADL - 19 Items Total Score.
Time frame: Baseline to Week 24
Efficacy of Memantine on Functioning Using CMAI - Long Form Total Score.
Time frame: Baseline to Week 24
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Dec 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 23472619Herrmann N, Gauthier S, Boneva N, Lemming OM; 10158 Investigators. A randomized, double-blind, placebo-controlled trial of memantine in a behaviorally enriched sample of patients with moderate-to-severe Alzheimer's disease. Int Psychogeriatr. 2013 Jun;25(6):919-27. doi: 10.1017/S1041610213000239. Epub 2013 Mar 8.
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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.
Email contact via H. Lundbeck A/S study director
LundbeckClinicalTrials@lundbeck.com
23 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Memantine in people with Alzheimer's Disease, run by H. Lundbeck A/S at 23 sites in Canada.
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 5 inclusion and 1 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: stopped early, as of the sponsor's last update on 5 Dec 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 23 sites in Canada. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Jan 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Efficacy of Memantine on Behavioural Symptoms in Outpatients With Moderate to Severe Dementia of the Alzheimer's Type Using the NPI - 12 Items Version Total Score. (time frame: Baseline to Week 24). 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?
On the ClinicalTrials.gov record for NCT00857649, which also lists 1 linked publication.
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 5 Dec 2013.