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| ID | Type | Description | Link |
|---|---|---|---|
| 2004-002614-10 | EudraCT Number |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Memantine | Experimental |
| |
| Placebo | Placebo Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Memantine | Drug | 10 mg tablets twice daily |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| 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) | Baseline to 1 year |
| Measure | Description | Time Frame |
|---|---|---|
| Changes in Total Hippocampal Volume (HCV) | Estimated mean changes in total HCV | Baseline to 1 year |
| Cognitive and Behavioural Outcomes: Controlled Oral Word Association Test (COWAT) Total Score |
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Inclusion Criteria:
Exclusion Criteria:
Other protocol-defined inclusion and exclusion criteria applied.
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| Name | Affiliation | Role |
|---|---|---|
| Email contact via H. Lundbeck A/S | LundbeckClinicalTrials@lundbeck.com | Study Director |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 22269160 | Result | 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. |
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After a 3-week run-in period during which MRI scans were performed, the patients were randomised to either placebo or memantine and stratified according to AChEI treatment. Memantine-treated patients started with 5 mg/day and were uptitrated by 5 mg/day every week for 4 weeks. The target dose of 20 mg/day was administered from the start of Week 4.
The patients were recruited from each investigator's outpatient clinic.
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| ID | Title | Description |
|---|---|---|
| FG000 | Memantine 10 mg Tablets Twice Daily | |
| FG001 | Placebo Tablets Twice Daily |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Memantine 10 mg Tablets Twice Daily | |
| BG001 | Placebo Tablets Twice Daily | |
| BG002 | Total |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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) | FAS-MRI: Full-analysis set for all patients in the all-patients-treated set (APTS) who had at least one valid MRI scan >=6 months after initiation of investigational medicinal product (IMP). The FAS (full analysis set, efficacy set) replaces the intention-to-treat (ITT) concept used in older terminology. | Posted | Mean | Standard Error | mL/year | Baseline to 1 year |
|
1 year
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Memantine 10 mg Tablets Twice Daily |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abnormal behaviour | Psychiatric disorders | MedDRA (11.1) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Agitation | Psychiatric disorders | MedDRA (11.1) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| H. Lundbeck A/S | H. Lundbeck A/S | +45 3630 1311 | LundbeckClinicalTrials@lundbeck.com |
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| ID | Term |
|---|---|
| D000544 | Alzheimer Disease |
| ID | Term |
|---|---|
| D003704 | Dementia |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
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| ID | Term |
|---|---|
| D008559 | Memantine |
| ID | Term |
|---|---|
| D000547 | Amantadine |
| D000218 | Adamantane |
| D001952 | Bridged-Ring Compounds |
| D006844 | Hydrocarbons, Cyclic |
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| Placebo | Drug | Tablets twice daily |
|
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
| 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 | Baseline to 1 year |
| Protocol Violation |
|
| Withdrawal by Subject |
|
| Non-compliance |
|
| Lost to Follow-up |
|
| Administrative or other reason(s) |
|
Total of all reporting groups
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Controlled Oral Word Association Test (COWAT): Baseline Efficacy 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. | Mean | Standard Deviation | Number of words |
|
| Category Fluency Test (CFT): Baseline Efficacy Scores | CFT: The patient was asked to, during 1 minute, say aloud as many different words as possible from the categories animals and fruits. The total score was calculated as the number of appropriate words generated, with higher scores indicating lower cognitive impairment. | Mean | Standard Deviation | Number of words |
|
| ADAS-cog-Orientation Test (ADAS-cog-OT): Baseline Efficacy Scores | ADAS-cog-OT: A subscale of the ADAS-cog test with 8 questions and designed to determine how well oriented the patient is with regard to time and place. The total score was calculated as 8 minus the total number of correct answers, with higher scores indicating greater cognitive impairment. | Mean | Standard Deviation | Points |
|
| Stroop Interference Test - Incongruent (SIT-I): Baseline Efficacy Scores | SIT-I: A test to demonstrate the reaction time. Names of colours are printed in a different ink than the colour named. The time taken to complete the test was recorded, as was the number of errors. The more time spent and the higher number of errors indicates lower reaction time. | Mean | Standard Deviation | Seconds |
|
| Stroop Interference Test - Congruent (SIT-C): Baseline Efficacy Scores | SIT-C: A test to demonstrate the reaction time. Names of colours are printed in the same ink as the colours named. The time taken to complete the test was recorded, as was the number of errors. The more time spent and the higher number of errors indicates lower reaction time. | Mean | Standard Deviation | Seconds |
|
| Mini Mental State Examination (MMSE): Baseline Efficacy 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. | Mean | Standard Deviation | Points |
|
| Neuropsychiatric Inventory (NPI): Baseline Efficacy Scores | NPI: A scale specifically developed to assess behavioural disturbances in patients with dementia. It is based on responses from the caregiver. The range is 0 to 120, with higher score reflecting higher frequency and severity of the disturbances. | Mean | Standard Deviation | Points |
|
| Magnetic Resonance Imaging (MRI) Descriptives | Mean | Standard Deviation | mL; mm^3 |
|
| Units | Counts |
|---|---|
| Participants |
|
|
|
| Secondary | Changes in Total Hippocampal Volume (HCV) | Estimated mean changes in total HCV | FAS-MRI | Posted | Mean | Standard Deviation | mm^3/year | Baseline to 1 year |
|
|
|
|
| Secondary | 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 | FAS, observed cases (OC) | Posted | Least Squares Mean | Standard Error | Scale scores | Baseline to 1 year |
|
|
|
|
| Secondary | 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 | FAS, OC | Posted | Least Squares Mean | Standard Error | Scale scores | Baseline to 1 year |
|
|
|
|
| 17 |
| 133 |
| 46 |
| 133 |
| EG001 | Placebo Tablets Twice Daily | 20 | 144 | 36 | 144 |
| Agitation | Psychiatric disorders | MedDRA (11.1) | Systematic Assessment |
|
| Anaemia | Blood and lymphatic system disorders | MedDRA (11.1) | Systematic Assessment |
|
| Angina pectoris | Cardiac disorders | MedDRA (11.1) | Systematic Assessment |
|
| Ankle fracture | Injury, poisoning and procedural complications | MedDRA (11.1) | Systematic Assessment |
|
| Aortic aneurysm rupture | Vascular disorders | MedDRA (11.1) | Systematic Assessment |
|
| Atrial fibrillation | Cardiac disorders | MedDRA (11.1) | Systematic Assessment |
|
| Balance disorder | Nervous system disorders | MedDRA (11.1) | Systematic Assessment |
|
| Benign prostatic hyperplasia [gs] | Reproductive system and breast disorders | MedDRA (11.1) | Systematic Assessment |
|
| Bronchitis | Infections and infestations | MedDRA (11.1) | Systematic Assessment |
|
| Cardiac failure | Cardiac disorders | MedDRA (11.1) | Systematic Assessment |
|
| Cerebral haemorrhage | Nervous system disorders | MedDRA (11.1) | Systematic Assessment |
|
| Cerebral infarction | Nervous system disorders | MedDRA (11.1) | Systematic Assessment |
|
| Cerebrovascular accident | Nervous system disorders | MedDRA (11.1) | Systematic Assessment |
|
| Cervical vertebral fracture | Injury, poisoning and procedural complications | MedDRA (11.1) | Systematic Assessment |
|
| Circulatory collapse | Vascular disorders | MedDRA (11.1) | Systematic Assessment |
|
| Contusion | Injury, poisoning and procedural complications | MedDRA (11.1) | Systematic Assessment |
|
| Convulsion | Nervous system disorders | MedDRA (11.1) | Systematic Assessment |
|
| Delirium | Psychiatric disorders | MedDRA (11.1) | Systematic Assessment |
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| Delusion | Psychiatric disorders | MedDRA (11.1) | Systematic Assessment |
|
| Dementia | Nervous system disorders | MedDRA (11.1) | Systematic Assessment |
|
| Disorientation | Psychiatric disorders | MedDRA (11.1) | Systematic Assessment |
|
| Diverticulum intestinal haemorrhagic | Gastrointestinal disorders | MedDRA (11.1) | Systematic Assessment |
|
| Fall | Injury, poisoning and procedural complications | MedDRA (11.1) | Systematic Assessment |
|
| Femoral neck fracture | Injury, poisoning and procedural complications | MedDRA (11.1) | Systematic Assessment |
|
| Gastrointestinal cancer metastatic | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (11.1) | Systematic Assessment |
|
| Gastrointestinal stoma complication | Injury, poisoning and procedural complications | MedDRA (11.1) | Systematic Assessment |
|
| Haemothorax | Respiratory, thoracic and mediastinal disorders | MedDRA (11.1) | Systematic Assessment |
|
| Hallucination | Psychiatric disorders | MedDRA (11.1) | Systematic Assessment |
|
| Hip fracture | Injury, poisoning and procedural complications | MedDRA (11.1) | Systematic Assessment |
|
| Humerus fracture | Injury, poisoning and procedural complications | MedDRA (11.1) | Systematic Assessment |
|
| Hypoglycaemia | Metabolism and nutrition disorders | MedDRA (11.1) | Systematic Assessment |
|
| Hypotension | Vascular disorders | MedDRA (11.1) | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA (11.1) | Systematic Assessment |
|
| Intestinal obstruction | Gastrointestinal disorders | MedDRA (11.1) | Systematic Assessment |
|
| Knee arthroplasty | Surgical and medical procedures | MedDRA (11.1) | Systematic Assessment |
|
| Lacunar infarction | Nervous system disorders | MedDRA (11.1) | Systematic Assessment |
|
| Lower respiratory tract infection | Infections and infestations | MedDRA (11.1) | Systematic Assessment |
|
| Pacemaker generated rhythm | Surgical and medical procedures | MedDRA (11.1) | Systematic Assessment |
|
| Paranoia | Psychiatric disorders | MedDRA (11.1) | Systematic Assessment |
|
| Partial seizures | Nervous system disorders | MedDRA (11.1) | Systematic Assessment |
|
| Pelvic fracture | Injury, poisoning and procedural complications | MedDRA (11.1) | Systematic Assessment |
|
| Prostate cancer [gs] | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (11.1) | Systematic Assessment |
|
| Radius fracture | Injury, poisoning and procedural complications | MedDRA (11.1) | Systematic Assessment |
|
| Renal failure acute | Renal and urinary disorders | MedDRA (11.1) | Systematic Assessment |
|
| Rib fracture | Injury, poisoning and procedural complications | MedDRA (11.1) | Systematic Assessment |
|
| Road traffic accident | Injury, poisoning and procedural complications | MedDRA (11.1) | Systematic Assessment |
|
| Sick sinus syndrome | Cardiac disorders | MedDRA (11.1) | Systematic Assessment |
|
| Sinoatrial block | Cardiac disorders | MedDRA (11.1) | Systematic Assessment |
|
| Social stay hospitalisation | Social circumstances | MedDRA (11.1) | Systematic Assessment |
|
| Somnolence | Nervous system disorders | MedDRA (11.1) | Systematic Assessment |
|
| Subileus | Gastrointestinal disorders | MedDRA (11.1) | Systematic Assessment |
|
| Syncope | Nervous system disorders | MedDRA (11.1) | Systematic Assessment |
|
| Thoracic vertebral fracture | Injury, poisoning and procedural complications | MedDRA (11.1) | Systematic Assessment |
|
| Transient ischaemic attack | Nervous system disorders | MedDRA (11.1) | Systematic Assessment |
|
| Urinary incontinence | Renal and urinary disorders | MedDRA (11.1) | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA (11.1) | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA (11.1) | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA (11.1) | Systematic Assessment |
|
| Fall | Injury, poisoning and procedural complications | MedDRA (11.1) | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA (11.1) | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA (11.1) | Systematic Assessment |
|
Publication of the results by the Investigator will be subject to mutual agreement between the Investigator and H. Lundbeck A/S. Manuscripts and abstracts must be sent to H. Lundbeck A/S at least one month prior to submission for publication or presentation.
| D024801 |
| Tauopathies |
| D019636 | Neurodegenerative Diseases |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
| D006838 |
| Hydrocarbons |
| D009930 | Organic Chemicals |