Alzheimer's Disease
Conditions
Keywords
double-blind, treatment, prazosin, Disruptive behaviors in Alzheimer's Disease
Brief summary
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
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.
Interventions
DRUGPrazosin
4 mg capsules twice daily for 12 weeks
DRUGPlacebo
Placebo capsules twice daily for 12 weeks
Sponsors
National Institute on Aging (NIA)
VA Puget Sound Health Care System
Seattle Institute for Biomedical and Clinical Research
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 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change | 12 Weeks after Baseline | 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. |
| Change in Neuropsychiatric Inventory Score | 12 weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Brief Psychiatric Rating Scale Total Score | 12 Weeks after Baseline | 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. |
| Days in Study | 12 weeks after Baseline | 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). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Prazosin 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.
Prazosin: 4 mg capsules twice daily for 12 weeks | 11 |
| Placebo 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.
Placebo: Placebo capsules twice daily for 12 weeks | 9 |
| Total | 20 |
Baseline characteristics
| Characteristic | Prazosin | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 82.4 years STANDARD_DEVIATION 10.5 | 78.7 years STANDARD_DEVIATION 8.2 | 80.7 years STANDARD_DEVIATION 9.5 |
| Brief Psychiatric Rating Scale | 45.4 units on a scale STANDARD_DEVIATION 9.1 | 44.2 units on a scale STANDARD_DEVIATION 9.5 | 44.9 units on a scale STANDARD_DEVIATION 9.1 |
| Sex: Female, Male Female | 6 Participants | 7 Participants | 13 Participants |
| Sex: Female, Male Male | 5 Participants | 2 Participants | 7 Participants |
| Total Neuropsychiatric Inventory score | 43.5 units on a scale STANDARD_DEVIATION 16.2 | 40.9 units on a scale STANDARD_DEVIATION 18.9 | 42.4 units on a scale STANDARD_DEVIATION 17.1 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 11 / 11 | 9 / 9 |
| serious Total, serious adverse events | 0 / 11 | 0 / 9 |
Outcome results
Primary
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.
Time frame: 12 Weeks after Baseline
Population: Any participant who had at least one follow-up assessment was included in the analysis. One participant in the Placebo group did not return for follow-up, and therefore was not included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prazosin | Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change | 2.5 units on a scale | Standard Deviation 0.25 |
| Placebo | Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change | 2.43 units on a scale | Standard Deviation 0.28 |
Primary
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.
Time frame: 12 weeks
Population: One study participant in the Placebo group dropped out prior to first follow-up, although this subject is included in the statistical analysis to provide information on the outcome at baseline.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prazosin | Change in Neuropsychiatric Inventory Score | -23.4 units on a scale | Standard Deviation 3.7 |
| Placebo | Change in Neuropsychiatric Inventory Score | -16.6 units on a scale | Standard Deviation 4.5 |
Secondary
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.
Time frame: 12 Weeks after Baseline
Population: One study participant in the Placebo group dropped out prior to first follow-up, although this subject is included in the statistical analysis to provide information on the outcome at baseline.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prazosin | Change in Brief Psychiatric Rating Scale Total Score | -9.8 units on a scale | Standard Deviation 2.3 |
| Placebo | Change in Brief Psychiatric Rating Scale Total Score | -7.7 units on a scale | Standard Deviation 2.8 |
Secondary
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).
Time frame: 12 weeks after Baseline
Population: 7 participants in the prazosin group were in the double-blind phase longer than 12 weeks (84 days). 4 participants in the placebo group were in the double-blind phase longer than 12 weeks (84 days).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prazosin | Days in Study | 87 days | Standard Deviation 8 |
| Placebo | Days in Study | 79 days | Standard Deviation 9 |