Memantine for Agitation and Aggression in 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: NCT00401167
Recruitment Status : Completed
First Posted : November 17, 2006
Last Update Posted : May 25, 2012
Lundbeck Canada Inc.
Information provided by (Responsible Party):
Sunnybrook Health Sciences Centre

Brief Summary:
Alzheimer's disease (AD) is the most common form of dementia and is characterized by both cognitive and behavioural symptoms ("Behavioural and Psychological Symptoms of Dementia"; BPSD). To date, there are only modestly effective treatments for BPSD, and these treatments are associated with an increased risk of mortality in elderly dementia patients. We plan to study whether treatment with medication memantine improves BPSD in severe AD patients. Thirty-two AD patients with significant BPSD, including agitation and aggression, will be treated for three months with memantine. Assessments of behavioural symptoms and global clinical outcomes will be completed after one, two and three months of treatment.

Condition or disease Intervention/treatment Phase
Alzheimer's Disease Drug: memantine Phase 4

Detailed Description:

BPSD in institutionalized patients with severe AD is a serious public health problem. The effectiveness of current pharmacological management of BPSD with atypical antipsychotics is modest at best, and there are serious safety concerns including increased cerebrovascular adverse events and increased mortality. Preliminary data with memantine suggests this medication may be helpful for treating BPSD in the severe subgroup of the Alzheimer's disease patient population. It is for this reason we propose an open-label prospective study of memantine in institutionalized patients with severe Alzheimer's disease and significant BPSD.

The major objective of this study is to examine the effectiveness of memantine on behaviour with a focus on agitation and aggression. The secondary objective is to determine the effect of memantine on nursing burden and prescription medication use. The study would expand clinical experience with memantine and provide information on professional caregiver burden and prescription medication use in this institutionalized, more severely impaired and frailer population. This information could be used to design a randomized placebo controlled confirmatory trial.

The effectiveness of memantine on agitation and aggression in patients with moderate to severe Alzheimer's disease will be assessed in a 3-month, open-label study involved 32 patients residing in long-term care facilities.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 32 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase IV-An Open-Label Prospective Study of Memantine in Institutionalized Patients With Severe Alzheimer's Disease and Significant Behavioural and Psychological Symptoms of Dementia
Study Start Date : November 2006
Actual Primary Completion Date : January 2010
Actual Study Completion Date : January 2010

Intervention Details:
  • Drug: memantine
    Following the baseline visit, subjects will receive memantine 5 mg OD for one week, followed by 5 mg BID for one week, followed by 10 mg QAM and 5 mg QPM for one week, followed by 10 mg BID for the following 9 weeks.

Primary Outcome Measures :
  1. Neuropsychiatric Inventory Nursing Home Version [ Time Frame: Screening, Baseline, 1 month, 2 months, 3 months ]
  2. Clinical Global Impression of Change [ Time Frame: Baseline, 1 month, 2 months, 3 months ]

Secondary Outcome Measures :
  1. Neuropsychiatric Inventory Nursing Home Version [ Time Frame: Screening, baseline, 1 month, 2 months, 3 months ]
  2. Neuropsychiatric Inventory Burden Subscale [ Time Frame: Screening, baseline, 1 month, 2 months, 3 months ]
  3. Cohen Mansfield Agitation Inventory [ Time Frame: Baseline, 1 month, 2 months, 3 months ]
  4. Modified Nursing Care Assessment Scale [ Time Frame: Baseline, 3 months ]
  5. Activities of Daily Living [ Time Frame: Baseline, 3 months ]
  6. Quality of Life in Late Stage Dementia [ Time Frame: Baseline, 3 months ]

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Ages Eligible for Study:   65 Years and older   (Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Signed informed consent obtained from a legally acceptable representative
  • Male or female > 65 years of age, residing in long-term care
  • Diagnosis and Statistical Manual of Mental Disorders (DSM-IV-TR) diagnosis of Dementia of the Alzheimer's type (code 290.1)
  • Mini Mental State Examination total score ≤ 15
  • Neuropsychiatric Inventory-Nursing Home Version total score > 10, and a score > 1 on the agitation/aggression subscale
  • A current order for any prescription medication for behavioral and psychological symptoms of dementia (e.g. benzodiazepine, antipsychotic, trazodone), with at least 1 dose used in the prior 3 months
  • Patients with a current order for any regularly administered psychotropic (example, selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, trazodone, atypical antipsychotics, typical antipsychotics or cholinesterase inhibitors) must have been on a stable dose for 3 months prior to entry

Exclusion Criteria:

  • Current evidence of any uncontrolled medical illness that would interfere with the subject's participation in the study
  • Dementia due to any etiology other than Alzheimer's Disease
  • Subjects experiencing significant difficulties ingesting oral medications

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): NCT00401167

Canada, Ontario
North York General Hospital
Toronto, Ontario, Canada, M2K 1E1
Sunnybrook Health Sciences Centre
Toronto, Ontario, Canada, M4N 3M5
Sponsors and Collaborators
Sunnybrook Health Sciences Centre
Lundbeck Canada Inc.
Principal Investigator: Nathan Herrmann, MD Sunnybrook Health Sciences Centre

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Sunnybrook Health Sciences Centre Identifier: NCT00401167     History of Changes
Other Study ID Numbers: Lundbeck-11267
First Posted: November 17, 2006    Key Record Dates
Last Update Posted: May 25, 2012
Last Verified: January 2010

Keywords provided by Sunnybrook Health Sciences Centre:
Alzheimer's disease
behavioral and psychological symptoms of dementia
severe Alzheimer's disease

Additional relevant MeSH terms:
Alzheimer Disease
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders
Behavioral Symptoms
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