A Clinical Study Evaluating the Effects of Memantine on Brain Atrophy in Patients With Alzheimer's Disease
Primary Purpose
Alzheimer's Disease
Status
Completed
Phase
Phase 4
Locations
Study Type
Interventional
Intervention
Memantine
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Alzheimer's Disease focused on measuring Memantine, Neuroimaging, MRI, Brain atrophy
Eligibility Criteria
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Memantine
Placebo
Arm Description
Outcomes
Primary Outcome Measures
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)
Secondary Outcome Measures
Changes in Total Hippocampal Volume (HCV)
Estimated mean changes in total HCV
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
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
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00862940
Brief Title
A Clinical Study Evaluating the Effects of Memantine on Brain Atrophy in Patients With Alzheimer's Disease
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
Study Type
Interventional
2. Study Status
Record Verification Date
August 2012
Overall Recruitment Status
Completed
Study Start Date
September 2005 (undefined)
Primary Completion Date
February 2009 (Actual)
Study Completion Date
April 2009 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
H. Lundbeck A/S
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief 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). 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alzheimer's Disease
Keywords
Memantine, Neuroimaging, MRI, Brain atrophy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
277 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Memantine
Arm Type
Experimental
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Memantine
Other Intervention Name(s)
Ebixa®
Intervention Description
10 mg tablets twice daily
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Tablets twice daily
Primary Outcome Measure Information:
Title
Total Brain Atrophy Rate Estimated Using Brain Boundary Shift Integral (BBSI)
Description
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)
Time Frame
Baseline to 1 year
Secondary Outcome Measure Information:
Title
Changes in Total Hippocampal Volume (HCV)
Description
Estimated mean changes in total HCV
Time Frame
Baseline to 1 year
Title
Cognitive and Behavioural Outcomes: Controlled Oral Word Association Test (COWAT) Total Score
Description
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
Time Frame
Baseline to 1 year
Title
Cognitive and Behavioural Outcomes: Mini Mental State Examination (MMSE) Total Score
Description
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
Time Frame
Baseline to 1 year
10. Eligibility
Sex
All
Minimum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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
Exclusion Criteria:
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Email contact via H. Lundbeck A/S
Organizational Affiliation
LundbeckClinicalTrials@lundbeck.com
Official's Role
Study Director
12. IPD Sharing Statement
Citations:
PubMed Identifier
22269160
Citation
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.
Results Reference
result
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A Clinical Study Evaluating the Effects of Memantine on Brain Atrophy in Patients With Alzheimer's Disease
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