Alzheimer Disease, Psychomotor Agitation
Conditions
Keywords
double-blind, treatment, prazosin
Brief summary
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
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.
Interventions
DRUGprazosin
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.
DRUGplacebo (inert substance)
Placebo is an inert substance used as a standard comparator in clinical pharmacologic trials. Duration is 8 weeks.
Sponsors
National Institute on Aging (NIA)
University of Washington
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Clinical Global Impression of Change (CGIC) at Last Observation | Week 8 | 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. |
| Change in Neuropsychiatric Inventory (NPI) Total Score Over the Course of Study Participation | Weeks 2, 4, 6, and 8 (change from Baseline) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Behavioral Assessment Visits Completed | Last behavioral assessment (Baseline, Weeks 1, 2, 4, 6, or 8) | This measure reflects the length of time participants remained in the study. There were 6 behavioral assessment visits included in the protocol. |
| Change in Brief Psychiatric Rating Scale (BPRS) Total Score Over the Course of Study Participation | Weeks 2, 4, 6, and 8 (change from Baseline) | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Prazosin 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. | 12 |
| Placebo Placebo is an inert substance used as a standard comparator in clinical pharmacologic trials. | 12 |
| Total | 24 |
Baseline characteristics
| Characteristic | Placebo | Prazosin | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 12 Participants | 12 Participants | 24 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age Continuous | 78.1 years STANDARD_DEVIATION 10.8 | 83.2 years STANDARD_DEVIATION 11.5 | 80.6 years STANDARD_DEVIATION 11.2 |
| Region of Enrollment United States | 12 participants | 12 participants | 24 participants |
| Sex: Female, Male Female | 6 Participants | 5 Participants | 11 Participants |
| Sex: Female, Male Male | 6 Participants | 7 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 6 / 12 | 9 / 12 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 |
Outcome results
Primary
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.
Time frame: Weeks 2, 4, 6, and 8 (change from Baseline)
Population: Participants with at least one follow-up behavioral assessment visit were included in this analysis.~The mean group change was calculated by calculating the mean of each participant's follow-up measures, subtracting this mean from the baseline value, and then from these values, calculating group means and standard deviations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prazosin | Change in Neuropsychiatric Inventory (NPI) Total Score Over the Course of Study Participation | -19 units on a scale | Standard Deviation 21 |
| Placebo | Change in Neuropsychiatric Inventory (NPI) Total Score Over the Course of Study Participation | -2 units on a scale | Standard Deviation 15 |
Primary
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.
Time frame: Week 8
Population: Participants with at least one follow-up behavioral assessment visit were included in this analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prazosin | Mean Clinical Global Impression of Change (CGIC) at Last Observation | 2.6 units on a scale | Standard Deviation 1 |
| Placebo | Mean Clinical Global Impression of Change (CGIC) at Last Observation | 4.5 units on a scale | Standard Deviation 1.6 |
Secondary
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.
Time frame: Weeks 2, 4, 6, and 8 (change from Baseline)
Population: Participants with at least one follow-up behavioral assessment visit were included in this analysis.~The mean group change was determined by calculating the mean of each participant's follow-up measures, subtracting this mean from the baseline value, and then from these values, calculating group means and standard deviations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prazosin | Change in Brief Psychiatric Rating Scale (BPRS) Total Score Over the Course of Study Participation | -9 units on a scale | Standard Deviation 9 |
| Placebo | Change in Brief Psychiatric Rating Scale (BPRS) Total Score Over the Course of Study Participation | -3 units on a scale | Standard Deviation 5 |
Secondary
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.
Time frame: Last behavioral assessment (Baseline, Weeks 1, 2, 4, 6, or 8)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prazosin | Number of Behavioral Assessment Visits Completed | 4.8 number of visits | Standard Deviation 1.6 |
| Placebo | Number of Behavioral Assessment Visits Completed | 4.5 number of visits | Standard Deviation 1.8 |