Memantine and Comprehensive, Individualized Management of Alzheimer's Disease and Caregiver Training

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine whether a comprehensive, individualized management approach with caregiver training and medication with memantine will alleviate symptoms in community dwelling patients with moderate to severe Alzheimer's disease.

Detailed Description
-----------------
Presently some 4.5 million people are afflicted with Alzheimer's disease in the United States. At present pharmacologic treatment, although beneficial, is not curative. Certain nonpharmacologic treatments have assisted caregivers of AD patients by reducing their stress and burden, and others have aided patients, by improving their mood and physical functioning. Comprehensive, individualized approaches to improving Alzheimer's patients' symptomatology and caregiver stress and burden have not been systematically investigated in Alzheimer's patient care. This study seeks to train and counsel caregivers as well as develop an individualized, comprehensive management program that will seek to enhance the functioning of each patient participant. Patients are randomly placed into one of two groups. Both groups receive memantine and comprehensive evaluations at baseline, 4, 12,28 and 52 weeks. Additionally, group 1 receives an individualized management program, which consists of home visits to get the patient exercising, doing enjoyable activities and cognitive stimulation, educational sessions for caregivers on coping with difficult situations and a caregiver support group to help with questions and emotional concerns.

Official Title
-----------------
Memantine and Comprehensive, Individualized, Patient Centered Management of Alzheimer's Disease: A Randomized Controlled Trial

Conditions
-----------------
Alzheimer's Disease

Intervention / Treatment
-----------------
* Behavioral: Individualized management of AD including caregiver training
* Drug: Memantine


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients, 50 years of age or greater, residing in the community Presence of a family and/or professional caregiver willing and able to participate in all aspects of this study A diagnosis of probable Alzheimer's disease by Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) and NINCDS-ADRDA (McKhann,et al., Neurology,1984;34: 939-944) criteria A CT or MRI brain scan and medical work up compatible with the DSM-IV and NINCDS-ADRDA diagnostic criteria for Alzheimer's disease Mini-Mental State Examination scores of 3-14 Global Deterioration Scale stages of 5 or 6 A stage of 6a or greater on the Functional Assessment Staging instrument signifying the presence of dementia deficits in the ability to perform one or more basic activities of daily living Exclusion Criteria: Non-English speaking patients and/or caregivers Subjects with a diagnosis of dementia due to conditions other than Alzheimer's disease. Subjects with a diagnosis of vascular dementia or a score greater than 4 on the modified Hachinski Ischemic Rating scale Patients with a major depressive disorder Patients with clinically significant laboratory abnormalities Patients receiving investigational pharmacologic agents

Ages Eligible for Study
-----------------
Minimum Age: 50 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1<br>Individualized Management including caregiver training and Memantine | Behavioral: Individualized management of AD including caregiver training<br>* Individualized management program: consists of home visits to get the patient exercising, doing enjoyable activities and cognitive stimulation, educational sessions for caregivers on coping with difficult situations and a caregiver support group to help with questions and emotional concerns.<br>* Other names: Alzheimer's Disease;Drug: Memantine<br>* Patients receive 10 milligrams of memantine twice daily.<br>* Other names: Namenda;|
| Active Comparator: Group 2<br>Only Memantine | Drug: Memantine<br>* Patients receive 10 milligrams of memantine twice daily.<br>* Other names: Namenda;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Clinician Interview-Based Assessment of Change Plus Caregiver Input (CIBIC-Plus) Global Score (New York Univeristy Version) | CIBIC-Plus is measured in units on a scale ranging from 1 to 7, where 1 is markedly improved, 4 is unchanged, and 7 is markedly worse | Baseline to 28 weeks | 
| Change From Baseline in Clinician Interview-Based Assessment of Change Plus Caregiver Input (CIBIC-Plus) Global Score (New York Univeristy Version) | CIBIC-Plus is measured in units on a scale ranging from 1 to 7, where 1 is markedly improved, 4 is unchanged, and 7 is markedly worse | Baseline to 52 weeks | 
| Change From Baseline of The Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory Modified for Severe Dementia Abbreviated Version (ADCS-ADLsev-abv) | The ADCS-ADLsev-abv is a structured questionnaire where each item consists of a series of hierarchical questions designed to determine a patient's ability to perform the activities of daily living as assessed by the caregiver. Possible scores range from 0 to 39, where a higher score is indicative of greater capacities. | Baseline to 28 weeks | 
| Change From Baseline of The Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory Modified for Severe Dementia Abbreviated Version (ADCS-ADLsev-abv) | The ADCS-ADLsev-abv is a structured questionnaire where each item consists of a series of hierarchical questions designed to determine a patient's ability to perform the activities of daily living as assessed by the caregiver. Possible scores range from 0 to 39, where a higher score is indicative of greater capacities. | Baseline to 52 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline of the Severe Impairment Battery (SIB) | The SIB evaluates cognitive performance. It is a 51 item scale which assesses social interaction, memory, language, orientation, attention, praxis, visuospacial ability and construction. Scores range from 0 (greatest impairment) to 100 (least impairment). | Baseline to 28 weeks | 
| Change From Baseline of the Severe Impairment Battery (SIB) | The SIB evaluates cognitive performance. It is a 51 item scale which assesses social interaction, memory, language, orientation, attention, praxis, visuospacial ability and construction. Scores range from 0 (greatest impairment) to 100 (least impairment). | Baseline to 52 weeks | 
| Change From Baseline of the Mini-Mental State Examination (MMSE) | The MMSE is a graded on a 30 point scale that measures cognitive functioning. A lower score indicates a higher level of impairment. Complete scale range is -no cognitive impairment=24-30; mild cognitive impairment=18-23; severe cognitive impairment=0-17. | Baseline to 28 weeks | 
| Change From Baseline of the Mini-Mental State Examination (MMSE) | The MMSE is a graded on a 30 point scale that measures cognitive functioning. A lower score indicates a higher level of impairment. Complete scale range is -no cognitive impairment=24-30; mild cognitive impairment=18-23; severe cognitive impairment=0-17. | Baseline to 52 weeks | 
| Change From Baseline of the Functional Assessment Staging Disability Score (FAST-DS) | The FAST-DS assesses the magnitude of progressive functional deterioration by identifying characteristic progressive disabilities in participants with AD. Scores range from 1.0 (normal) to 7f (severe loss of ability, not even able to hold up head independently). Scores are made up of stages (1 through 7) and substages (from a to e for stage 6; from a to f for stage 7). The following scoring for substages is applied: 6a=6.0, 6b=6.2, 6c=6.4, 6d=6.6, 6e=6.8, 7a=7.0, 7b=7.2, 7c=7.4, 7d=7.6, 7e=7.8, 7f=8.0. Additionally, non-consecutive deficits are noted and scored as follows: full stage non-consecutive deficit=1.0, non-consecutive substage deficit=0.2. The overall FAST-DS score = (FAST Stage Score) + (Each Non-Consecutive FAST disability scored as described) | Baseline to 28 weeks | 
| Change From Baseline of the Functional Assessment Staging Disability Score (FAST-DS) | The FAST-DS assesses the magnitude of progressive functional deterioration by identifying characteristic progressive disabilities in participants with AD. Scores range from 1.0 (normal) to 7f (severe loss of ability, not even able to hold up head independently). Scores are made up of stages (1 through 7) and substages (from a to e for stage 6; from a to f for stage 7). The following scoring for substages is applied: 6a=6.0, 6b=6.2, 6c=6.4, 6d=6.6, 6e=6.8, 7a=7.0, 7b=7.2, 7c=7.4, 7d=7.6, 7e=7.8, 7f=8.0. Additionally, non-consecutive deficits are noted and scored as follows: full stage non-consecutive deficit=1.0, non-consecutive substage deficit=0.2. The overall FAST-DS score = (FAST Stage Score) + (Each Non-Consecutive FAST disability scored as described) | Baseline to 52 weeks | 
| Change From Baseline of The Behavioral Pathology in Alzheimer's Disease Frequency Weighted Severity Scale (BEHAVE-AD-FW) | The BEHAVE-AD-FW measures the frequency and severity of 25 behavioral symptoms with a total score and global rating. Individual behavioral assessments are rated for severity (0=none to 3-most severe) and frequency (1=least frequent to 4=most frequent) which are then multiplied; scores for each of the 25 items are then summed. Possible total scores range from 0 to 297. The global rating is scored from 0 (not dangerous to patient, not troubling to caregiver) to 3 (dangerous to patient, highly troubling to caregiver). Global rating was not analyzed for this study. The higher the score the worse the outcome. | Baseline to 28 weeks | 
| Change From Baseline of The Behavioral Pathology in Alzheimer's Disease Frequency Weighted Severity Scale (BEHAVE-AD-FW) | The BEHAVE-AD-FW measures the frequency and severity of 25 behavioral symptoms with a total score and global rating. Individual behavioral assessments are rated for severity (0=none to 3-most severe) and frequency (1=least frequent to 4=most frequent) which are then multiplied; scores for each of the 25 items are then summed. Possible total scores range from 0 to 297. The global rating is scored from 0 (not dangerous to patient, not troubling to caregiver) to 3 (dangerous to patient, highly troubling to caregiver). The higher the score the worse the outcome. | Baseline to 52 weeks | 
| Change From Baseline of the Revised Memory and Behavior Problems Checklist (RMBPC): Frequency | The RMBPC is a 24 item rating scale of the frequency of memory and behavioral problems in the AD subject and of how upset or bothered their caregivers react. Frequency is rated from 0 (least frequent) to 4 (most frequent) and caregiver reaction is rated from 0 (not at all) to 4 (extremely bothered or upset). Higher scores indicate more frequent memory and behavioral problems in the subject with AD as well as a more upset or bothered caregiver. Possible scores range from 0 to 96. | Baseline to 28 weeks | 
| Change From Baseline of the Revised Memory and Behavior Problems Checklist (RMBPC): Caregiver Reaction | The RMBPC is a 24 item rating scale of the frequency of memory and behavioral problems in the AD subject and of how upset or bothered their caregivers react. Frequency is rated from 0 (least frequent) to 4 (most frequent) and caregiver reaction is rated from 0 (not at all) to 4 (extremely bothered or upset). Higher scores indicate more frequent memory and behavioral problems in the subject with AD as well as a more upset or bothered caregiver. Possible scores range from 0 to 96. | Baseline to 28 weeks | 
| Change From Baseline of the Revised Memory and Behavior Problems Checklist (RMBPC): Frequency | The RMBPC is a 24 item rating scale of the frequency of memory and behavioral problems in the AD subject and of how upset or bothered their caregivers react. Frequency is rated from 0 (least frequent) to 4 (most frequent) and caregiver reaction is rated from 0 (not at all) to 4 (extremely bothered or upset). Higher scores indicate more frequent memory and behavioral problems in the subject with AD as well as a more upset or bothered caregiver. Possible scores range from 0 to 96. | Baseline to 52 weeks | 
| Change From Baseline of the Revised Memory and Behavior Problems Checklist (RMBPC): Caregiver Reaction | The RMBPC is a 24 item rating scale of the frequency of memory and behavioral problems in the AD subject and of how upset or bothered their caregivers react. Frequency is rated from 0 (least frequent) to 4 (most frequent) and caregiver reaction is rated from 0 (not at all) to 4 (extremely bothered or upset). Higher scores indicate more frequent memory and behavioral problems in the subject with AD as well as a more upset or bothered caregiver. Possible scores range from 0 to 96. | Baseline to 52 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Alzheimer's disease, caregiver training, caregiver counseling, individualized management, memantine, dementia