Alzheimer's in Long-Term Care--Treatment for Agitation

Study Overview
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Brief Summary
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The purpose of this study is to see if a medication called prazosin is useful in the treatment of agitation and aggression in persons with Alzheimer's disease (AD) and other types of dementia in late life.

Detailed Description
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Although the occurrence of disruptive agitation behaviors likely are influenced by environmental/ interpersonal factors, it is also likely that behaviorally relevant neurobiologic abnormalities lower the threshold for the expression of such behavior in Alzheimer's disease. Because of the success prazosin has had in the treatment of Posttraumatic Stress Disorder, it is thought that it could be used similarly with disruptive agitation. Originally designed to evaluate Alzheimer's disease patients in nursing homes, the study now includes outpatients. It is a 9-week placebo-controlled trial.

Official Title
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Alzheimer's in Long-Term Care--Treatment for Agitation

Conditions
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Alzheimer Disease, Psychomotor Agitation

Intervention / Treatment
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* Drug: prazosin
* Drug: placebo (inert substance)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: No age limit probable/possible Alzheimer's disease diagnosis disruptive agitated behaviors (e.g., irritability, aggression, uncooperativeness, pacing) no hypotension no concurrent use of alpha-1-blockers no delirium, schizophrenia, mania, psychotic symptoms. Exclusion Criteria: Cardiovascular: unstable angina, recent myocardial infarction, second or third degree atrioventricular (AV) block, preexisting hypotension (systolic blood pressure less than 110) or orthostatic hypotension Other medical exclusions: chronic renal or hepatic failure, or any unstable medical condition Exclusionary medications: current treatment with prazosin, other alpha-1-blockers Current enrollment in a separate investigational drug trial Psychoactive medications: subjects may be psychoactive medication-free or be partial responders (by subjective assessment of referring health care professional) to one psychoactive medication from any of the following classes: antipsychotics, anticonvulsants, mood stabilizers, antidepressants, benzodiazepines, or buspirone. Partial response is defined as some improvement in agitated behavior but persistence of agitated behaviors severe enough to cause patient distress and/or difficulty with caregiving. Although not formally rated, this improvement is equivalent to a Clinical Global Impression of Change (CGIC) rating of no more than minimal improvement (improvement is noticed by not enough to improve patient function or caregiver's practical management of the patient). Psychiatric/behavioral: lifetime schizophrenia; current delirium, mania, depression, or uncontrolled persistent distressing psychotic symptoms (hallucinations, delusions), substance abuse, panic disorder, or any behavior which poses an immediate danger to patient or others or which results in the patient being too uncooperative to meet the requirements of study participation.
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: prazosin<br> | Drug: prazosin<br>* Participants taking prazosin. Prazosin was administered as 1 or 2 mg capsules. Doses were initiated at 1 mg at bedtime. Titration based on tolerability was conducted up to a dose of 2 mg in the morning plus 4mg at bedtime. Duration was 8 weeks.<br>* Other names: Minipress;|
| Placebo Comparator: placebo (inert substance)<br> | Drug: placebo (inert substance)<br>* Placebo is an inert substance used as a standard comparator in clinical pharmacologic trials. Duration is 8 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Clinical Global Impression of Change (CGIC) at Last Observation | The Clinical Global Impression of Change (CGIC) is a 7 point scale, where 1 indicates markedly improved, 4 indicates no change, and 7 indicates markedly worse. | Week 8 | 
| Change in Neuropsychiatric Inventory (NPI) Total Score Over the Course of Study Participation | The Neuropsychiatric Inventory (NPI) is a 12-item scale that assesses the frequency and severity of behavioral symptoms in patients with dementia. Each Neuropsychiatric Inventory item ranges from 0 to 12. Therefore the Neuropsychiatric Inventory total score has a minimum total value of 0 and maximum 144, where 144 indicates higher levels of behavioral symptoms. A change in Neuropsychiatric Inventory total score that is a negative number (that is, an Neuropsychiatric Inventory score decrease), indicates behavioral improvement. | Weeks 2, 4, 6, and 8 (change from Baseline) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Behavioral Assessment Visits Completed | This measure reflects the length of time participants remained in the study. There were 6 behavioral assessment visits included in the protocol. | Last behavioral assessment (Baseline, Weeks 1, 2, 4, 6, or 8) | 
| Change in Brief Psychiatric Rating Scale (BPRS) Total Score Over the Course of Study Participation | The Brief Psychiatric Rating Scale (BPRS) is an 18-item scale that rates psychiatric symptoms. Each item ranges from 1 to 7. Therefore, the Brief Psychiatric Rating Scale total score ranges from a minimum of 0 to a maximum of 126, where 126 indicates higher levels of behavioral symptoms. A change Brief Psychiatric Rating Scale score that is a negative number (that is, a Brief Psychiatric Rating Scale score decrease), indicates behavioral improvement. | Weeks 2, 4, 6, and 8 (change from Baseline) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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double-blind, treatment, prazosin