Clinical trial NCT00862940: 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
Overall status: COMPLETED
Phase: PHASE4
Conditions: Alzheimer's Disease
Keywords: Memantine
Neuroimaging
MRI
Brain atrophy
Lead sponsor: H. Lundbeck A/S
Sponsor class: INDUSTRY
First posted: 2009-03-17
Enrollment: 277
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Total Brain Atrophy Rate Estimated Using Brain Boundary Shift Integral (BBSI)
timeFrame: Baseline to 1 year
Secondary outcomes:
measure: Changes in Total Hippocampal Volume (HCV)
timeFrame: Baseline to 1 year
measure: Cognitive and Behavioural Outcomes: Controlled Oral Word Association Test (COWAT) Total Score
timeFrame: Baseline to 1 year
measure: Cognitive and Behavioural Outcomes: Mini Mental State Examination (MMSE) Total Score
timeFrame: Baseline to 1 year
Other outcomes:
Locations:
Study officials:
affiliation: LundbeckClinicalTrials@lundbeck.com
name: Email contact via H. Lundbeck A/S
role: STUDY_DIRECTOR
References:
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.