Prazosin Treatment for Disruptive Agitation in Alzheimer's Disease

• Sponsor: Seattle Institute for Biomedical and Clinical Research (Other)
• Overall Status: Completed
• CT.gov ID: NCT01126099
• Collaborator: National Institute on Aging (NIA) (NIH), VA Puget Sound Health Care System (U.S. Fed)
• Enrollment: 20
• Location: 1
• Arms: 2
• Duration (Months): 48
• Patients Per Site Per Month: 0.4

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Alzheimer's Disease	Drug: Prazosin; Drug: Placebo	N/A

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 20 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Prazosin Treatment for Disruptive Agitation in Alzheimer's Disease
• Study Start Date: Mar 1, 2010
• Actual Primary Completion Date: Mar 1, 2014
• Actual Study Completion Date: Mar 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: Prazosin; 4 mg capsules twice daily for 12 weeks; Other Names: minipress
Placebo Comparator: 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.	Drug: Placebo; Placebo capsules twice daily for 12 weeks; Other Names: inert substance

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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 Outcome Measures

1. 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.

2. 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).

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 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.

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

• Seattle Institute for Biomedical and Clinical Research
• National Institute on Aging (NIA)
• VA Puget Sound Health Care System

Investigators

• Principal Investigator: Elaine R Peskind, MD, University of Washington, VA Puget Sound Health Care System

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Seattle Institute for Biomedical and Clinical Research
• ClinicalTrials.gov Identifier: NCT01126099
• Other Study ID Numbers: 1R01AG033133-01A1; 5R01AG033133
• First Posted: May 19, 2010
• Last Update Posted: May 21, 2015
• Last Verified: May 1, 2015

• Keywords provided by Seattle Institute for Biomedical and Clinical Research: double-blind; treatment; prazosin; Disruptive behaviors in Alzheimer's Disease
• Additional relevant MeSH terms: Alzheimer Disease; Prazosin

Study Results

Participant Flow

Arm/Group Title	Prazosin	Placebo
Arm/Group Description	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	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
Period Title: Double Blind Phase
STARTED	11	9
COMPLETED	7	7
NOT COMPLETED	4	2
Period Title: Double Blind Phase
STARTED	5	7
COMPLETED	4	6
NOT COMPLETED	1	1

Baseline Characteristics

Arm/Group Title	Prazosin	Placebo	Total
Arm/Group Description	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	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	Total of all reporting groups
Overall Participants	11	9	20
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	82.4 (10.5)	78.7 (8.2)	80.7 (9.5)
Sex: Female, Male (Count of Participants)
Female	6 54.5%	7 77.8%	13 65%
Male	5 45.5%	2 22.2%	7 35%
Total Neuropsychiatric Inventory score (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	43.5 (16.2)	40.9 (18.9)	42.4 (17.1)
Brief Psychiatric Rating Scale (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	45.4 (9.1)	44.2 (9.5)	44.9 (9.1)

Outcome Measures

1. Primary Outcome

Title	Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Prazosin	Placebo
Arm/Group Description	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	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
Measure Participants	11	8
Mean (Standard Deviation) [units on a scale]	2.5 (.25)	2.43 (.28)

2. Secondary Outcome

Title	Change in Brief Psychiatric Rating Scale Total Score
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Prazosin	Placebo
Arm/Group Description	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	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
Measure Participants	11	9
Mean (Standard Deviation) [units on a scale]	-9.8 (2.3)	-7.7 (2.8)

3. Primary Outcome

Title	Change in Neuropsychiatric Inventory Score
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Prazosin	Placebo
Arm/Group Description	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	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
Measure Participants	11	9
Mean (Standard Deviation) [units on a scale]	-23.4 (3.7)	-16.6 (4.5)

4. Secondary Outcome

Title	Days in Study
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Prazosin	Placebo
Arm/Group Description	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	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
Measure Participants	11	9
Mean (Standard Deviation) [days]	87 (8)	79 (9)

Adverse Events

Time Frame	12 weeks.
Adverse Event Reporting Description	Known, common side effects for prazosin were specifically queried at each study visit.
Arm/Group Title	Prazosin		Placebo
Arm/Group Description	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		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
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	0/11 (0%)		0/9 (0%)
Other (Not Including Serious) Adverse Events
	Prazosin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/11 (100%)		9/9 (100%)
Blood and lymphatic system disorders
lower extremity edema	3/11 (27.3%)	3	2/9 (22.2%)	2
Gastrointestinal disorders
nausea	2/11 (18.2%)	2	1/9 (11.1%)	1
vomiting	1/11 (9.1%)	1	2/9 (22.2%)	2
diarrhea	2/11 (18.2%)	2	0/9 (0%)	0
gastrointestinal discomfort	2/11 (18.2%)	2	0/9 (0%)	0
General disorders
low energy	4/11 (36.4%)	4	4/9 (44.4%)	4
dizziness	5/11 (45.5%)	5	1/9 (11.1%)	1
decreased appetite	2/11 (18.2%)	2	1/9 (11.1%)	1
sleep disturbance	0/11 (0%)	0	2/9 (22.2%)	2
Infections and infestations
wound infection	0/11 (0%)	0	3/9 (33.3%)	3
Musculoskeletal and connective tissue disorders
musculoskeletal pain	2/11 (18.2%)	2	2/9 (22.2%)	2
Nervous system disorders
drowsiness	7/11 (63.6%)	7	1/9 (11.1%)	1
headache	3/11 (27.3%)	3	1/9 (11.1%)	1
Psychiatric disorders
increased agitation	0/11 (0%)	0	2/9 (22.2%)	2
Renal and urinary disorders
urinary tract infection	1/11 (9.1%)	1	3/9 (33.3%)	3
nocturnal enuresis	2/11 (18.2%)	2	0/9 (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.