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

• ClinicalTrials.gov Identifier: NCT00161473
• Recruitment Status: Completed
• First Posted: September 12, 2005
• Results First Posted: August 2, 2012
• Last Update Posted: August 2, 2012
• Sponsor: University of Washington
• Collaborator: National Institute on Aging (NIA)
• Information provided by (Responsible Party): University of Washington

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Conditions: Alzheimer Disease; Psychomotor Agitation
• Interventions: Drug: prazosin; Drug: placebo (inert substance)
• Enrollment: 24

Participant Flow

Recruitment Details
Pre-assignment Details

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 Number of Baseline Participants		12	12	24
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	12 participants	12 participants	24 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	0 0.0%	0 0.0%	0 0.0%
	>=65 years	12 100.0%	12 100.0%	24 100.0%
Age Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	12 participants	12 participants	24 participants
		83.2 (11.5)	78.1 (10.8)	80.6 (11.2)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	12 participants	12 participants	24 participants
	Female	5 41.7%	6 50.0%	11 45.8%
	Male	7 58.3%	6 50.0%	13 54.2%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	12 participants	12 participants	24 participants
		12	12	24

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.
Overall Number of Participants Analyzed	11	11
Mean (Standard Deviation); Unit of Measure: 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.
Overall Number of Participants Analyzed	11	11
Mean (Standard Deviation); Unit of Measure: 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.
Overall Number of Participants Analyzed	12	12
Mean (Standard Deviation); Unit of Measure: 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.
Overall Number of Participants Analyzed	11	11
Mean (Standard Deviation); Unit of Measure: 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 (%)		Affected / at Risk (%)
Total	--/--		--/--
Serious Adverse Events
	Prazosin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0.00%)		0/12 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Prazosin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/12 (50.00%)		9/12 (75.00%)
Nervous system disorders
sedation †	3/12 (25.00%)	3	3/12 (25.00%)	3
confusion †	1/12 (8.33%)	1	4/12 (33.33%)	4
headache †	0/12 (0.00%)	0	2/12 (16.67%)	2
Psychiatric disorders
hallucinations †	1/12 (8.33%)	1	1/12 (8.33%)	1
Respiratory, thoracic and mediastinal disorders
cough †	2/12 (16.67%)	2	0/12 (0.00%)	0
Skin and subcutaneous tissue disorders
rash †	0/12 (0.00%)	0	1/12 (8.33%)	1
Vascular disorders
lower extremity edema †	1/12 (8.33%)	1	2/12 (16.67%)	2
hypotension †	2/12 (16.67%)	2	1/12 (8.33%)	1
dizziness on standing †	1/12 (8.33%)	1	0/12 (0.00%)	0
† Indicates events were collected by systematic assessment

Limitations and 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.

Results Point of Contact

• Name/Title: Lucy Y. Wang, M.D.
• Organization: VA Puget Sound Healthcare System
• Phone: 206-277-5089
• EMail: wanglucy@u.washington.edu

Publications of Results:

Wang LY, Shofer JB, Rohde K, Hart KL, Hoff DJ, McFall YH, Raskind MA, Peskind ER. Prazosin for the treatment of behavioral symptoms in patients with Alzheimer disease with agitation and aggression. Am J Geriatr Psychiatry. 2009 Sep;17(9):744-51. doi: 10.1097/JGP.0b013e3181ab8c61.

• Responsible Party: University of Washington
• ClinicalTrials.gov Identifier: NCT00161473
• Other Study ID Numbers: 16508-A; 5R01AG018644 ( U.S. NIH Grant/Contract ); 5P50AG005136 ( U.S. NIH Grant/Contract )
• First Submitted: September 8, 2005
• First Posted: September 12, 2005
• Results First Submitted: February 24, 2012
• Results First Posted: August 2, 2012
• Last Update Posted: August 2, 2012