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

• Sponsor: University of Washington (Other)
• Overall Status: Completed
• CT.gov ID: NCT00161473
• Collaborator: National Institute on Aging (NIA) (NIH)
• Enrollment: 24
• Location: 1
• Arms: 2
• Duration (Months): 104
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Alzheimer Disease; Psychomotor Agitation	Drug: prazosin; Drug: placebo (inert substance)	N/A

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 24 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Alzheimer's in Long-Term Care--Treatment for Agitation
• Study Start Date: Jan 1, 2001
• Actual Primary Completion Date: Sep 1, 2009
• Actual Study Completion Date: Sep 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: prazosin	Drug: 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. Duration was 8 weeks.; Other Names: Minipress
Placebo Comparator: placebo (inert substance)	Drug: placebo (inert substance); Placebo is an inert substance used as a standard comparator in clinical pharmacologic trials. Duration is 8 weeks.

Outcome Measures

Primary Outcome Measures

1. 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."

2. 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 Outcome Measures

1. 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.

2. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: All
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Veterans Affairs Puget Sound Health Care System	Seattle	Washington	United States	98108

Sponsors and Collaborators

• University of Washington
• National Institute on Aging (NIA)

Investigators

• Principal Investigator: Elaine R Peskind, MD, Veterans Affairs Puget Sound Health Care System

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Washington
• ClinicalTrials.gov Identifier: NCT00161473
• Other Study ID Numbers: 16508-A; 5R01AG018644; 5P50AG005136
• First Posted: Sep 12, 2005
• Last Update Posted: Aug 2, 2012
• Last Verified: Jun 1, 2012

• Keywords provided by University of Washington: double-blind; treatment; prazosin
• Additional relevant MeSH terms: Alzheimer Disease; Psychomotor Agitation; Prazosin

Study Results

Participant Flow

Arm/Group Title	Prazosin	Placebo
Arm/Group Description	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.	Placebo is an inert substance used as a standard comparator in clinical pharmacologic trials.
Period Title: Overall Study
STARTED	12	12
COMPLETED	7	6
NOT COMPLETED	5	6

Baseline Characteristics

Arm/Group Title	Prazosin	Placebo	Total
Arm/Group Description	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.	Placebo is an inert substance used as a standard comparator in clinical pharmacologic trials.	Total of all reporting groups
Overall Participants	12	12	24
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	0 0%	0 0%	0 0%
>=65 years	12 100%	12 100%	24 100%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	83.2 (11.5)	78.1 (10.8)	80.6 (11.2)
Sex: Female, Male (Count of Participants)
Female	5 41.7%	6 50%	11 45.8%
Male	7 58.3%	6 50%	13 54.2%
Region of Enrollment (participants) [Number]
United States	12 100%	12 100%	24 100%

Outcome Measures

1. Primary Outcome

Title	Mean Clinical Global Impression of Change (CGIC) at Last Observation
Description	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

Outcome Measure Data

Analysis Population Description

Participants with at least one follow-up behavioral assessment visit were included in this analysis

Arm/Group Title	Prazosin	Placebo
Arm/Group Description	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.	Placebo is an inert substance used as a standard comparator in clinical pharmacologic trials.
Measure Participants	11	11
Mean (Standard Deviation) [units on a scale]	2.6 (1.0)	4.5 (1.6)

2. Primary Outcome

Title	Change in Neuropsychiatric Inventory (NPI) Total Score Over the Course of Study Participation
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Prazosin	Placebo
Arm/Group Description	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.	Placebo is an inert substance used as a standard comparator in clinical pharmacologic trials.
Measure Participants	11	11
Mean (Standard Deviation) [units on a scale]	-19 (21)	-2 (15)

3. Secondary Outcome

Title	Number of Behavioral Assessment Visits Completed
Description	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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Prazosin	Placebo
Arm/Group Description	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.	Placebo is an inert substance used as a standard comparator in clinical pharmacologic trials.
Measure Participants	12	12
Mean (Standard Deviation) [number of visits]	4.8 (1.6)	4.5 (1.8)

4. Secondary Outcome

Title	Change in Brief Psychiatric Rating Scale (BPRS) Total Score Over the Course of Study Participation
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Prazosin	Placebo
Arm/Group Description	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.	Placebo is an inert substance used as a standard comparator in clinical pharmacologic trials.
Measure Participants	11	11
Mean (Standard Deviation) [units on a scale]	-9 (9)	-3 (5)

Adverse Events

Time Frame	Adverse event data were collected from informed consent up until volunteers reached the end of their participation per protocol. Monitoring period was 10-12 weeks (2-4 weeks to start and titrate study drug, plus the 8 week follow-up period).
Adverse Event Reporting Description	Adverse effects were collected at each study visit. Study staff inquired about specific symptoms known to be potential side effects of prazosin using a preexisting checklist. Participants and their study companions were also asked about any new changes in health or medications.
Arm/Group Title	Prazosin		Placebo
Arm/Group Description	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.		Placebo is an inert substance used as a standard comparator in clinical pharmacologic trials.
All Cause Mortality
	Prazosin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Prazosin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/12 (0%)
Other (Not Including Serious) Adverse Events
	Prazosin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/12 (50%)		9/12 (75%)
Nervous system disorders
sedation	3/12 (25%)	3	3/12 (25%)	3
confusion	1/12 (8.3%)	1	4/12 (33.3%)	4
headache	0/12 (0%)	0	2/12 (16.7%)	2
Psychiatric disorders
hallucinations	1/12 (8.3%)	1	1/12 (8.3%)	1
Respiratory, thoracic and mediastinal disorders
cough	2/12 (16.7%)	2	0/12 (0%)	0
Skin and subcutaneous tissue disorders
rash	0/12 (0%)	0	1/12 (8.3%)	1
Vascular disorders
lower extremity edema	1/12 (8.3%)	1	2/12 (16.7%)	2
hypotension	2/12 (16.7%)	2	1/12 (8.3%)	1
dizziness on standing	1/12 (8.3%)	1	0/12 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.