CompletedPhase 4Results posted

A Clinical Study Evaluating the Effects of Memantine on Brain Atrophy in Patients With Alzheimer's Disease

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

Lead sponsor

H. Lundbeck A/S

Asset

Memantine

Listed sites

Recruiting sites

Enrollment

277

actual

Study population

Alzheimer’s disease

Key I/E criteria

•Alzheimer's disease•MMSE 12-20•Study partner/caregiver required

Primary endpoint

•Total Brain Atrophy Rate Estimated

Identifiers

Registered as

Org study ID10112

Eudract number2004-002614-10

NCT IDNCT00862940

Timeline

Milestones

Study start2005-09 (month precision)

Primary completion2009-02actual (month precision)

Study first posted2009-03-17estimated

Study completion2009-04actual (month precision)

Results first posted2011-06-03estimated

Last update posted2012-09-03estimated

Assets

Drug assets

Memantine

Study populations

Who this study enrolls

Alzheimer’s disease

Eligibility

Who can enroll

Minimum age50 Years

SexAll

Healthy volunteersNot accepted

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.

Endpoints (8)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

Neuroimaging

Global cognition

Executive function / language

Global cognition

2 endpoints

Secondary/protocol endpoint

Cognitive and Behavioural Outcomes: Mini Mental State Examination (MMSE) Total Score

Time frame:Baseline to 1 year

Mini-Mental State Examination (MMSE)

change from baseline, improvement

Secondary/registry result

Cognitive and Behavioural Outcomes: Mini Mental State Examination (MMSE) Total Score

Time frame:Baseline to 1 year

Mini-Mental State Examination (MMSE)

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Scale scores	Standard error
Memantine 10 mg Tablets Twice Dailyn=108 Participants	-0.50	0.45
Placebo Tablets Twice Dailyn=114 Participants	-0.74	0.44

Mean Difference (Final Values)0.2495% CI-0.67 - 1.15p0.602MMRM

Executive function / language

2 endpoints

Secondary/protocol endpoint

Cognitive and Behavioural Outcomes: Controlled Oral Word Association Test (COWAT) Total Score

Time frame:Baseline to 1 year

change from baseline, improvement

Secondary/registry result

Cognitive and Behavioural Outcomes: Controlled Oral Word Association Test (COWAT) Total Score

Time frame:Baseline to 1 year

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Scale scores	Standard error
Memantine 10 mg Tablets Twice Dailyn=106 Participants	0.78	0.71
Placebo Tablets Twice Dailyn=114 Participants	-0.90	0.69

Mean Difference (Final Values)1.6895% CI0.13 - 3.23p0.034MMRM

Neuroimaging

4 endpoints

Primary/protocol endpoint

Total Brain Atrophy Rate Estimated Using Brain Boundary Shift Integral (BBSI)

Time frame:Baseline to 1 year

descriptive

Primary/registry result

Total Brain Atrophy Rate Estimated Using Brain Boundary Shift Integral (BBSI)

Time frame:Baseline to 1 year

descriptive

Posted result

Group	Value (mean), mL/year	Standard error
Memantine 10 mg Tablets Twice Dailyn=110 Participants	15.24	0.97
Placebo Tablets Twice Dailyn=118 Participants	15.32	0.91

Adjusted mean difference-0.0495% CI-2.60 - 2.52p0.9754Mixed Models Analysis

Secondary/protocol endpoint

Changes in Total Hippocampal Volume (HCV)

Time frame:Baseline to 1 year

descriptive

Secondary/registry result

Changes in Total Hippocampal Volume (HCV)

Time frame:Baseline to 1 year

descriptive

Posted result

Group	Value (mean), mm^3/year	Standard deviation
Memantine 10 mg Tablets Twice Dailyn=95 Participants	-218	182
Placebo Tablets Twice Dailyn=109 Participants	-220	171

Adjusted mean difference-3.5095% CI-38.04 - 31.04p0.842MMRM

Mixed model repeated measurements (MMRM) with unstructured covariance including time, time-by-treatment, visit, pre-treatment HCV, and AChEI group.

Publications (1)

Bibliography

Records linked to this trial through ClinicalTrials.gov references, PubMed NCT search, and curated study seeds. 'Canonical' marks design/result papers; others are registry references or candidates.

Registry references + supporting bibliography

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.
PMID22269160via RESULT

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateJuly 21, 2026

Endpoint classificationDelfa ADRD endpoint taxonomy

Results tableClinicalTrials.gov results section

Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 21, 2026 snapshot.