Prazosin Treatment for Disruptive Agitation in Alzheimer's Disease

Study Overview
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Brief Summary
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A study of outpatient participants with Alzheimer's disease or a related dementia who have difficult behaviors that are upsetting for them or their caregivers. Prazosin is a medication that is commonly used to treat people with high blood pressure. Research with prazosin has shown that it may be effective in treating behavioral problems by reducing excess adrenalin effects in the brain.

Detailed Description
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This is a 24 week study with 14 visits to the research clinic. Approximately 6 of these visits may be done by phone. Additional phone checks are scheduled at the beginning of each 12 week part of the study. Participants will have a 50:50 chance of being on prazosin or placebo in the first 12 weeks of the study. For the second 12 weeks, all participants will take prazosin. Study visits include a physical and neurological exam; memory testing; interviews with the caregiver about behaviors; and vital signs.

Official Title
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Prazosin Treatment for Disruptive Agitation in Alzheimer's Disease

Conditions
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Alzheimer's Disease

Intervention / Treatment
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* Drug: Prazosin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: No age limit Probable or Possible Alzheimer's Disease Disruptive agitated behaviors at least twice a week (overly anxious or excited, making offensive comments.....) Stable medications for 2 weeks Must have a caregiver who spends 10 hours per week caring for the participant and agrees to participate in all evaluation sessions Exclusion Criteria: Cardiovascular: unstable angina, recent myocardial infarction, preexisting hypotension (systolic BP less than 110) or orthostatic hypotension (≥20 mmHg drop in systolic BP following 2 minutes of standing posture) Any unstable medical condition Exclusionary medications: current treatment with prazosin, other alpha-1 blockers (trazodone, sildenafil, vardenafil or tadalafil) 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 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 |
| --- | --- |
| Experimental: Prazosin<br>In the double blind phase (12 weeks), study participants will take either prazosin for placebo. For the open label phase (12 weeks), all study participants will take prazosin. | Drug: Prazosin<br>* 4 mg capsules twice daily for 12 weeks<br>* Other names: minipress;|
| Placebo Comparator: Placebo<br>In the double blind phase (12 weeks), study participants will take either prazosin for placebo. For the open label phase (12 weeks), all study participants will take prazosin. | Drug: Placebo<br>* Placebo capsules twice daily for 12 weeks<br>* Other names: inert substance;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change | This scale represents the raters overall impression of improvement or worsening, and is assessed at the last visit. 1 = Marked improvement, 1 = Moderate improvement, 3 = Minimal improvement, 4 = No change, 5 = Minimal worsening, 6 = Moderate worsening, 7 = Marked worsening. | 12 Weeks after Baseline | 
| Change in Neuropsychiatric Inventory Score | Neuropsychiatric Inventory score change from Baseline to last observation.The Neuropsychiatric Inventory is a scale that quantifies behavioral and psychiatric symptoms in patients with dementia. The scale ranges from 0 to 144, with 0 being no symptoms. | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Brief Psychiatric Rating Scale Total Score | Brief Psychiatric Rating Scale score change from Baseline to last observation. The Brief Psychiatric Rating Scale measures 18 psychiatric symptom domains. The scale ranges from 18 to 126, where 18 indicates no psychiatric symptoms. | 12 Weeks after Baseline | 
| Days in Study | The number of days participants remained in the study during the Double Blind Phase. Please note that although the length of follow-up designated in the protocol was 12 weeks, a number of participants were in this phase longer (e.g. the dose titration phase took longer than 3 weeks, assessments were delayed due to scheduling conflicts, etc.) Therefore the length of time in the Double Blind Phase can exceed 12 weeks (84 days). | 12 weeks after Baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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double-blind, treatment, prazosin, Disruptive behaviors in Alzheimer's Disease