Clinical trial NCT00401167: Memantine for Agitation and Aggression in Severe Alzheimer's Disease
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Alzheimer's Disease
Keywords: Alzheimer's disease
behavioral and psychological symptoms of dementia
severe Alzheimer's disease
memantine
agitation
aggression
Lead sponsor: Sunnybrook Health Sciences Centre
Sponsor class: OTHER
Collaborators: name: Lundbeck Canada Inc.
First posted: 2006-11-17
Enrollment: 31
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Neuropsychiatric Inventory Nursing Home Version
timeFrame: Screening, Baseline, 1 month, 2 months, 3 months
measure: Clinical Global Impression of Change
timeFrame: Baseline, 1 month, 2 months, 3 months
Secondary outcomes:
measure: Neuropsychiatric Inventory Nursing Home Version
timeFrame: Screening, baseline, 1 month, 2 months, 3 months
measure: Neuropsychiatric Inventory Burden Subscale
timeFrame: Screening, baseline, 1 month, 2 months, 3 months
measure: Cohen Mansfield Agitation Inventory
timeFrame: Baseline, 1 month, 2 months, 3 months
measure: Modified Nursing Care Assessment Scale
timeFrame: Baseline, 3 months
measure: Activities of Daily Living
timeFrame: Baseline, 3 months
measure: Quality of Life in Late Stage Dementia
timeFrame: Baseline, 3 months
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: North York General Hospital
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
Study officials:
affiliation: Sunnybrook Health Sciences Centre
name: Nathan Herrmann, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Herrmann N, Cappell J, Eryavec GM, Lanctot KL. Changes in nursing burden following memantine for agitation and aggression in long-term care residents with moderate to severe Alzheimer's disease: an open-label pilot study. CNS Drugs. 2011 May;25(5):425-33. doi: 10.2165/11588160-000000000-00000.