Alzheimer's DiseasePhase 4NCT00862940
A Clinical Study Evaluating the Effects of Memantine on Brain Atrophy in Patients With Alzheimer's Disease
A Phase 4 study testing Memantine in people with Alzheimer's Disease, run by H. Lundbeck A/S.
Trial summary
Pre-clinical studies have demonstrated that memantine can decrease the neuronal toxicity associated with excessive glutamate release and calcium overload in neurons. Previous studies have shown that memantine helps to treat the symptoms of Alzheimer's Disease (AD). 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
- 277 participants
- Where
- No sites listed yet
- Study dates
- Sep 2005to Apr 2009
- Phase
- Phase 4
- 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 at least 50 years of age with a current diagnosis of probable AD of moderate severity (MMSE score between 12 and 20, inclusive) consistent with NINCDS-ADRDA criteria and MRI scans
- Patients must have had a knowledgeable and reliable caregiver to accompany them to all clinic visits during the study
- Patients were either on or off existing acetylcholinesterase inhibitor (AChEI) treatment provided that the treatment had been initiated >6 months prior to screening, had stabilised with respect to dose for >3 months, and remained fixed during the entire study. AChEI treatment could not be initiated or modified during the study
Who cannot join
- The patient had evidence of clinically significant active disease (including recent myocardial infarction and uncompensated congestive heart failure [NYHA II-IV])
- The patient had evidence of any clinically significant neurodegenerative disease or neurological disorder other than AD
- The patient was contraindicated for MRI
- Other protocol-defined inclusion and exclusion criteria applied.
About this study
Official title: A 1-year Randomised, Double-blind Placebo-controlled Study to Evaluate the Effects of Memantine on Rate of Brain Atrophy in Patients With Alzheimer's Disease
Pre-clinical studies have demonstrated that memantine can decrease the neuronal toxicity associated with excessive glutamate release and calcium overload in neurons. Previous studies have shown that memantine helps to treat the symptoms of Alzheimer's Disease (AD). In AD, the rate of brain tissue loss, or atrophy, is faster than in normal aging and this seems to go hand in hand with some of the symptoms of the disease. This suggests that memantine treatment in AD could provide both symptomatic improvement and neuro-protective effects. The purpose of this study was to show whether memantine, in addition to providing symptomatic benefits, can slow the rate of brain atrophy as assessed using magnetic resonance imaging (MRI) technology.
Read the detailed description
The primary objective of this study was to evaluate the effects of memantine on the rate of brain atrophy compared to placebo in patients with AD (moderate severity) over a 1-year period. This was a multinational, randomised, double-blind, parallel-group, placebo-controlled, fixed-dose study (20 mg memantine). The study also included secondary imaging, cognitive and behavioural measures.
- Conditions
- Alzheimer's Disease
- Being tested
- Memantine, Placebo
- Keywords
- Memantine, Neuroimaging, MRI, Brain atrophy
- 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®
10 mg tablets twice daily
PlaceboDrug
Tablets twice 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.
Total Brain Atrophy Rate Estimated Using Brain Boundary Shift Integral (BBSI)
Measures direct changes in total brain volume per visit interval (screening to Week 4, 42, or 52 or from Week 4 to Week 42 or 52)
Measured: Baseline to 1 year
Secondary outcomes (3)
Changes in Total Hippocampal Volume (HCV)
Estimated mean changes in total HCV
Measured: Baseline to 1 year
Cognitive and Behavioural Outcomes: Controlled Oral Word Association Test (COWAT) Total Score
Adjusted mean change from baseline on cognitive and behavioural scores. COWAT: Verbal fluency test. The patient was asked to, during 1 minute, generate as many words as possible beginning with three pre-specified letters. The total score was calculated as the sum of acceptable words generated, with higher scores indicating lower cognitive impairment
Measured: Baseline to 1 year
Cognitive and Behavioural Outcomes: Mini Mental State Examination (MMSE) Total Score
Adjusted mean change from baseline on cognitive and behavioural scores. MMSE: Brief, structured examination of mental status that assesses orientation, memory, attention, naming, comprehension, and praxis. The range is 0 to 30, with a lower score indicating a worse mental state
Measured: Baseline to 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Mar 2009 (estimated)
- Study startSep 2005
- Primary completionFeb 2009
- Study completionApr 2009
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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 277 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
- NCT00862940
- Sponsor's protocol ID
- 10112
- Other IDs
- 2004-002614-10, 2004
- Status last verified
- Aug 2012
- First submitted
- 16 Mar 2009
- Last updated
- 3 Sep 2012
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Wilkinson D, Fox NC, Barkhof F, Phul R, Lemming O, Scheltens P. Memantine and brain atrophy in Alzheimer's disease: a 1-year randomized controlled trial. J Alzheimers Dis. 2012;29(2):459-69. doi: 10.3233/JAD-2011-111616.
PubMed 22269160
Study at a glance
From the registry record, last updated by the sponsor on 3 Sep 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A 1-year Randomised, Double-blind Placebo-controlled Study to Evaluate the Effects of Memantine on Rate of Brain Atrophy in Patients With Alzheimer's Disease
- ClinicalTrials.gov ID
- NCT00862940
- Acronym / sponsor ID
- 10112
- Conditions
- Alzheimer's Disease
- Keywords
- Memantine, Neuroimaging, MRI, Brain atrophy
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 277 participants (actual)
- Lead sponsor
- H. Lundbeck A/SIndustry (pharma, biotech, devices)
- Study start
- Sep 2005
- Primary completion
- Feb 2009 (actual)
- Study completion
- Apr 2009 (actual)
- First posted
- 17 Mar 2009 (estimated)
- Results
- Posted 3 Jun 2011
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Pre-clinical studies have demonstrated that memantine can decrease the neuronal toxicity associated with excessive glutamate release and calcium overload in neurons. Previous studies have shown that memantine helps to treat the symptoms of Alzheimer's Disease (AD). In AD, the rate of brain tissue loss, or atrophy, is faster than in normal aging and this seems to go hand in hand with some of the symptoms of the disease. This suggests that memantine treatment in AD could provide both symptomatic improvement and neuro-protective effects. The purpose of this study was to show whether memantine, in addition to providing symptomatic benefits, can slow the rate of brain atrophy as assessed using magnetic resonance imaging (MRI) technology.
Detailed description
The primary objective of this study was to evaluate the effects of memantine on the rate of brain atrophy compared to placebo in patients with AD (moderate severity) over a 1-year period. This was a multinational, randomised, double-blind, parallel-group, placebo-controlled, fixed-dose study (20 mg memantine). The study also included secondary imaging, cognitive and behavioural measures.
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 (3 listed)
- Outpatients at least 50 years of age with a current diagnosis of probable AD of moderate severity (MMSE score between 12 and 20, inclusive) consistent with NINCDS-ADRDA criteria and MRI scans
- Patients must have had a knowledgeable and reliable caregiver to accompany them to all clinic visits during the study
- Patients were either on or off existing acetylcholinesterase inhibitor (AChEI) treatment provided that the treatment had been initiated >6 months prior to screening, had stabilised with respect to dose for >3 months, and remained fixed during the entire study. AChEI treatment could not be initiated or modified during the study
Key exclusion criteria (4 listed)
- The patient had evidence of clinically significant active disease (including recent myocardial infarction and uncompensated congestive heart failure [NYHA II-IV])
- The patient had evidence of any clinically significant neurodegenerative disease or neurological disorder other than AD
- The patient was contraindicated for MRI
- Other protocol-defined inclusion and exclusion criteria applied.
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®10 mg tablets twice daily | Drug | Memantine |
| PlaceboTablets twice daily | Drug | Placebo |
Primary outcome
Total Brain Atrophy Rate Estimated Using Brain Boundary Shift Integral (BBSI)
Time frame: Baseline to 1 year
Measures direct changes in total brain volume per visit interval (screening to Week 4, 42, or 52 or from Week 4 to Week 42 or 52)
3 secondary outcomes
Changes in Total Hippocampal Volume (HCV)
Time frame: Baseline to 1 year
Cognitive and Behavioural Outcomes: Controlled Oral Word Association Test (COWAT) Total Score
Time frame: Baseline to 1 year
Cognitive and Behavioural Outcomes: Mini Mental State Examination (MMSE) Total Score
Time frame: Baseline to 1 year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Sep 2012.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 22269160Wilkinson D, Fox NC, Barkhof F, Phul R, Lemming O, Scheltens P. Memantine and brain atrophy in Alzheimer's disease: a 1-year randomized controlled trial. J Alzheimers Dis. 2012;29(2):459-69. doi: 10.3233/JAD-2011-111616.
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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
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Memantine in people with Alzheimer's Disease, run by H. Lundbeck A/S.
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 3 inclusion and 4 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: finished, as of the sponsor's last update on 3 Sep 2012. Status can change between updates, so confirm with the study contact before making plans.
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?
Yes. Results are posted in the registry (first posted 3 Jun 2011). 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?
Total Brain Atrophy Rate Estimated Using Brain Boundary Shift Integral (BBSI) (time frame: Baseline to 1 year). 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 NCT00862940, 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 3 Sep 2012.