Efficacy and Safety of Memantine in Moderate to Severe Alzheimer's Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00857649
Recruitment Status : Terminated
First Posted : March 6, 2009
Results First Posted : January 9, 2012
Last Update Posted : December 5, 2013
Information provided by (Responsible Party):
H. Lundbeck A/S

Brief Summary:
The primary objective of this study is to examine the efficacy of memantine on cognition and behavioural symptoms in outpatients with moderate to severe dementia of the Alzheimer's type.

Condition or disease Intervention/treatment Phase
Alzheimer's Disease Drug: Memantine Drug: Placebo Phase 3

Detailed Description:

Memantine is a moderate affinity, uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist. Pre-clinical studies have demonstrated that memantine can decrease the neuronal toxicity associated with excessive glutamate release and calcium overload in neurons. Results from clinical trials in patients with moderate to severe Alzheimer's Disease (AD) have demonstrated memantine's efficacy and safety by showing positive treatment effects on cognitive, global and functional decline.

This 24-week randomised, double-blind, placebo-controlled, multicentre study examines the effect of memantine 20 mg, administered once daily, on cognitive and behavioural symptoms in outpatients diagnosed with moderate to severe AD and significant psychopathology.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 369 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Randomised, Double-Blind, Parallel-Group Study Examining the Efficacy and Safety of Memantine in Patients With Moderate to Severe Dementia of the Alzheimer's Type
Study Start Date : December 2003
Actual Primary Completion Date : April 2010
Actual Study Completion Date : September 2010

Arm Intervention/treatment
Experimental: Memantine Drug: Memantine
20 mg Oral Tablets Once Daily
Other Name: Ebixa®

Placebo Comparator: Placebo Drug: Placebo
Oral Tablets Once Daily

Primary Outcome Measures :
  1. Efficacy of Memantine on Behavioural Symptoms in Outpatients With Moderate to Severe Dementia of the Alzheimer's Type Using the NPI - 12 Items Version Total Score. [ Time Frame: Baseline to Week 24 ]

    Change from Baseline in Neuropsychiatric Inventory (NPI) total score.

    NPI is a validated scale that assesses behavioural disturbances in patients with dementia. The 12 item version consists of 10 behavioural and 2 neurovegetative areas. It provides both a total score as well as scores for a number of sub-scales. The frequency, severity and caregiver distress for each domain are measured. The NPI is based upon responses obtained from the caregiver. The total score is from 0 to 144. A higher score reflects more frequency and severity of the disturbances.

  2. Efficacy of Memantine on Cognition in Outpatients With Moderate to Severe Dementia of the Alzheimer's Type Using the SIB Total Score. [ Time Frame: Baseline to Week 24 ]

    Change from Baseline in Severe Impairment Battery (SIB) total score.

    SIB is a validated scale used to assess cognitive function in patients with moderate to severe dementia. Items are single words or one-step commands combined with gestures. Nine domains are assessed, and the total score is between 0 and 100. A lower total score reflects the loss of cognitive function.

Secondary Outcome Measures :
  1. Efficacy of Memantine on Global Condition Using CIBIC-plus. [ Time Frame: Baseline to Week 24 ]

    Clinician's Interview-Based Impression of Change-Plus Version (CIBIC-plus). Improvement evaluated with reference to Baseline.

    CIBIC-plus is a global rating that is derived through an independent, comprehensive interview with the patient and caregiver by a rater who is barred from knowledge of all other psychometric test scores conducted as part of this protocol as well as from reported safety data. The rating is made on a 7-point scale ranging from "1 = marked improvement" to "7 = marked worsening". A score of "4" indicates no change.

  2. Efficacy of Memantine on Functioning Using ADCS-ADL - 19 Items Total Score. [ Time Frame: Baseline to Week 24 ]

    Change from Baseline on the Alzheimer's Disease Cooperative Study - Activities of Daily Living Inventory (ADCS-ADL) 19-item version total score.

    ADCS-ADL- 19 items version for moderate to severe AD will measure patient's functioning. This battery of ADL questions is used here to measure the functional capabilities of patients with dementia. The inventory is done by interviewing a person in close contact with the patient and covers the most usual and consistent performance of the patient over the preceding 4 weeks. Total score is from 0 to 54. The higher score, the lower impairment.

  3. Efficacy of Memantine on Functioning Using CMAI - Long Form Total Score. [ Time Frame: Baseline to Week 24 ]

    Change from Baseline on the Cohen-Mansfield Agitation Inventory (CMAI) - Long Form total score.

    CMAI - Long Form looks specifically at agitated behaviour in patients with cognitive impairment. It is a seven-point rating scale assessing the frequency of up to 29 agitated behaviours, ranging from "1 = Never" to "7 = Several times an hour". Rating is based on responses obtained from interviews with the caregiver. The total score ranges from 29 to 203, with a higher score reflecting more frequent behavioural disturbances.

Information from the National Library of Medicine

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Ages Eligible for Study:   50 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

Outpatients who:

  • had a primary diagnosis of probable Alzheimer's Disease (AD) according to National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINDS-ADRDA) criteria, and with Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revised (DSM IV TR) criteria for dementia of the Alzheimer's type
  • had moderate to severe dementia, defined as a Mini Mental State Examination (MMSE) total score >=5 and <=15 at screening. Before substantial protocol amendment SA04 (dated 7 October 2004) was implemented, the MMSE total score range at screening was >=8 and <=18. Substantial protocol amendment SA07 (dated 4 September 2009) allowed patients who had previously had an MMSE score of 16 or 17 to be re-screened >6 months after their initial screening and, if there was documented evidence of cognitive decline, to be enrolled in the study
  • had a Neuropsychiatric Inventory (NPI) total score >=13 and an NPI agitation/aggression subitem score >=1 at screening and baseline
  • did not have vascular dementia or a modified Hachinski Ischaemia Scale score >4 at screening

Exclusion Criteria:

  • Evidence of clinically significant active disease, evidence of other neurological disorders, and previous treatment with memantine

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00857649

Canada, Alberta
Edmonton, Alberta, Canada, T5G 0B7
Canada, British Columbia
Kelowna, British Columbia, Canada, V1W 4V5
Canada, Manitoba
Winnipeg, Manitoba, Canada, R3M 0X9
Canada, New Brunswick
St. John, New Brunswick, Canada
Canada, Nova Scotia
Kentville, Nova Scotia, Canada, B4N 4K9
Pictou, Nova Scotia, Canada, B0K 1H0
Canada, Ontario
Burlington, Ontario, Canada, L7M 4Y1
Orangeville, Ontario, Canada, L9W 2E1
Ottawa, Ontario, Canada, K1N 5C8
Peterborough, Ontario, Canada, K9H 2P4
Toronto, Ontario, Canada, M3B 2W7
Windsor, Ontario, Canada, N8X 5A6
Canada, Quebec
Beauport, Quebec, Canada, G1J 2G3
Greenfield Park, Quebec, Canada, J4V 2J2
Montreal, Quebec, Canada, H1T 2M4
Sherbrooke, Quebec, Canada, J1J 2B8
Sherbrooke, Quebec, Canada, J1J 3H5
Vanier, Quebec, Canada, G1M 2R9
Verdun, Quebec, Canada, H4H 1R3
Canada, Saskatchewan
Regina, Saskatchewan, Canada, S4T 1A5
Saskatoon, Saskatchewan, Canada, S7N 0W8
Kelowna, Canada, V1Y 3G8
Penticton, Canada, V2A 5C8
Sponsors and Collaborators
H. Lundbeck A/S
Study Director: Email contact via H. Lundbeck A/S

Publications of Results:
Responsible Party: H. Lundbeck A/S Identifier: NCT00857649     History of Changes
Other Study ID Numbers: 10158
First Posted: March 6, 2009    Key Record Dates
Results First Posted: January 9, 2012
Last Update Posted: December 5, 2013
Last Verified: November 2013

Keywords provided by H. Lundbeck A/S:
Alzheimer's Disease

Additional relevant MeSH terms:
Alzheimer Disease
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders
Antiparkinson Agents
Anti-Dyskinesia Agents
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents