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”

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.

Study Type: Interventional

Study Design: Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Efficacy Study

Study Primary Completion Date: July 2009

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.

Intervention(s) in this Clinical Trial

• 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 Measures

• Neuropsychiatric Inventory Nursing Home Version
  • Time Frame: Screening, Baseline, 1 month, 2 months, 3 months
    Safety Issue?: No
• Clinical Global Impression of Change
  • Time Frame: Baseline, 1 month, 2 months, 3 months
    Safety Issue?: No

Secondary Measures

• Neuropsychiatric Inventory Nursing Home Version
  • Time Frame: Screening, baseline, 1 month, 2 months, 3 months
    Safety Issue?: No
• Neuropsychiatric Inventory Burden Subscale
  • Time Frame: Screening, baseline, 1 month, 2 months, 3 months
    Safety Issue?: No
• Cohen Mansfield Agitation Inventory
  • Time Frame: Baseline, 1 month, 2 months, 3 months
    Safety Issue?: No
• Modified Nursing Care Assessment Scale
  • Time Frame: Baseline, 3 months
    Safety Issue?: No
• Activities of Daily Living
  • Time Frame: Baseline, 3 months
    Safety Issue?: No
• Quality of Life in Late Stage Dementia
  • Time Frame: Baseline, 3 months
    Safety Issue?: 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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 65 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Sunnybrook Health Sciences Centre

Overall Clinical Trial Officials and Contacts

Nathan Herrmann, MD Principal Investigator Sunnybrook Health Sciences Centre  

Overall Contact: Krista Lanctot, PhD 416-480-6100 krista.lanctot@sunnybrook.ca

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00401167

Study ID Number: Lundbeck-11267

ClinicalTrials.gov Identifier: NCT00401167

Health Authority: Canada: Health Canada