Augmentation Trial of Prazosin for Post-Traumatic Stress Disorder (PTSD)

• Sponsor: Seattle Institute for Biomedical and Clinical Research (Other)
• Overall Status: Completed
• CT.gov ID: NCT00990106
• Collaborator: United States Department of Defense (U.S. Fed), VA Puget Sound Health Care System (U.S. Fed), National Institute on Alcohol Abuse and Alcoholism (NIAAA) (NIH)
• Enrollment: 67
• Locations: 2
• Arms: 2
• Duration (Months): 42
• Patients Per Site: 33.5
• Patients Per Site Per Month: 0.8

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether prazosin will:

• reduce the incidence of nightmares and sleep disturbance

• increase functioning and sense of well being in combat-trauma exposed Operation Iraqi Freedom/Operation Enduring Freedom (OIF/OEF) Veterans.

Condition or Disease	Intervention/Treatment	Phase
Stress Disorders, Post-Traumatic; Combat Disorders; Sleep Disorders	Drug: prazosin hydrochloride; Drug: placebo	N/A

Detailed Description

This is a 15-week randomized parallel design, double-blind, placebo-controlled augmentation trial of prazosin to evaluate the efficacy and tolerability of prazosin augmentation in the treatment of PTSD trauma-related nightmares, sleep disturbance, global function and sense of well-being, and other clinical features and comorbidities of PTSD. Participants will be 210 OIF/OEF soldiers and veterans who have suffered war zone trauma. Participants will be randomized 1:1 to prazosin or placebo and all previous psychotropic medications and/or psychotherapy will be maintained constant. Randomization will be stratified by site and use of an antidepressant.

Study Design

• Study Type: Interventional
• Actual Enrollment: 67 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Placebo-Controlled Augmentation Trial of Prazosin for PTSD
• Study Start Date: Sep 1, 2009
• Actual Primary Completion Date: Mar 1, 2013
• Actual Study Completion Date: Mar 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: prazosin hydrochloride prazosin Pfizer Minipress oral capsules Subject will be titrated up to the optimum tolerated dose based on the Dosing Algorithm. Males and females will be titrated differently with females titrated slower and to a lower maximum daily dose.	Drug: prazosin hydrochloride; Subject will be titrated up to the optimum tolerated dose based on the Dosing Algorithm. Males and females will be titrated differently with females titrated slower and to a lower maximum daily dose. The first dose will be taken while the participant is in bed for the night to avoid orthostatic syncope, an uncommon but recognized "first dose" effect of prazosin or any alpha-1 antagonist if started at a high dose. The first dose effect is avoidable by starting treatment with a low dose (1 mg at bedtime) then titrating the dose upward gradually.; Other Names: prazosin Pfizer Minipress
Placebo Comparator: placebo placebo oral capsules Subject will be titrated up to the optimum tolerated dose based on the Dosing Algorithm. Males and females will be titrated differently with females titrated slower and to a lower maximum daily dose.	Drug: placebo; placebo; Other Names: sugar pill

Outcome Measures

Primary Outcome Measures

1. Change in Clinician Administered PTSD Scale for DSM-IV (CAPS) Recurrent Distressing Dreams Item [Baseline to Week 15]

   Item B-2 "recurrent distressing dreams of the event" is a single item from the Clinician Administered PTSD Scale. The rating consists of two parts: Frequency and Intensity. Symptom frequency rated 0 to 4. Symptom intensity rated 0 to 4. Frequency plus Intensity ratings equal the total score. A higher score is worse; a lower score is better. This outcome measure evaluates the change in score from Baseline to Week 15.

2. Change in Pittsburgh Sleep Quality Index (PSQI) [Baseline to Week 15]

   Pittsburgh Sleep Quality Index is a self-report questionnaire assessing sleep quality and disturbances over a 1-month time interval. A global score is obtained by summing the seven component subscales (total score range: 0-21). A score of 5 or less indicates good sleep quality. A score of more than 5 indicates poor sleep quality. Change is measured from Baseline to Week 15.

3. Clinical Global Impression of Change (CGIC) [Change from Baseline to Week 15]

   The Clinical Global Impression of Change is a 7-point scale that rates global change compared to baseline (1=markedly improved, 2=moderately improved, 3=minimally improved, 4=no change, 5=minimally worse, 6=moderately worse, 7=markedly worse). The CGIC is used to determine the impact of treat effects on meaningful and distinct change in overall sense of well-being and functioning. This outcome measures the proportion of responders who were rated markedly or moderately improved at Week 15 compared to Baseline.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria

• Age >18 years;

• Clear evidence of exposure to one or more war zone trauma events sufficient to satisfy DSM-IV criterion A1 for diagnosis of PTSD;

• DSM-IV diagnosis of PTSD derived from the CAPS; CAPS total score >50;

• CAPS Recurrent Distressing Dreams item score >5 (of maximum score of 8);

• stable dose of non-exclusionary medications and psychotherapeutic treatment for at least 4 weeks prior to randomization;

• good general medical health.

• Female participants must agree to use a reliable form of birth control during the study.

Exclusion Criteria

• Psychiatric/Behavioral - meets DSM-IV criteria for current schizophrenia, schizoaffective disorder, psychotic disorder, delirium, or any DSM-IV cognitive disorder; substance dependence disorder within 3 months or any current substance dependence; current cocaine or stimulant abuse; severe psychiatric instability or severe situational life crises, including evidence of being actively suicidal or homicidal, or any behavior which poses an immediate danger to patient or others.

• Medical - acute or unstable chronic medical illness, including unstable angina, recent myocardial infarction (within 6 months), congestive heart failure, preexisting hypotension or orthostatic hypotension, chronic renal or hepatic failure, pancreatitis, Meniere's disease, benign positional vertigo; narcolepsy, or diagnosed sleep apnea; allergy or previous adverse reaction to prazosin or other alpha-1 antagonist.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	VA Puget Sound Health Care System	Seattle	Washington	United States	98108
2	Madigan Army Medical Center	Tacoma	Washington	United States	98431

Sponsors and Collaborators

• Seattle Institute for Biomedical and Clinical Research
• United States Department of Defense
• VA Puget Sound Health Care System
• National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Investigators

• Study Chair: Murray Raskind, MD, Department of Veterans Affairs 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: NCT00990106
• Other Study ID Numbers: PT074250; 1P20AA017839-01
• First Posted: Oct 6, 2009
• Last Update Posted: May 23, 2018
• Last Verified: Apr 1, 2018

• Keywords provided by Seattle Institute for Biomedical and Clinical Research: posttraumatic stress disorder; PTSD; nightmares; prazosin; sleep disturbance; combat trauma
• Additional relevant MeSH terms: Sleep Wake Disorders; Disease; Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic; Combat Disorders; Prazosin

Study Results

Participant Flow

Arm/Group Title	Prazosin Hydrochloride	Placebo
Arm/Group Description	prazosin hydrochloride: Subject will be titrated up to the optimum tolerated dose based on the Dosing Algorithm. Males and females will be titrated differently with females titrated slower and to a lower maximum daily dose. The first dose will be taken while the participant is in bed for the night to avoid orthostatic syncope, an uncommon but recognized "first dose" effect of prazosin or any alpha-1 antagonist if started at a high dose. The first dose effect is avoidable by starting treatment with a low dose (1 mg at bedtime) then titrating the dose upward gradually.	placebo: placebo titrated in the same manner as prazosin arm.
Period Title: Overall Study
STARTED	32	35
COMPLETED	23	23
NOT COMPLETED	9	12

Baseline Characteristics

Arm/Group Title	Prazosin Hydrochloride	Placebo	Total
Arm/Group Description	prazosin hydrochloride: Subject will be titrated up to the optimum tolerated dose based on the Dosing Algorithm. Males and females will be titrated differently with females titrated slower and to a lower maximum daily dose. The first dose will be taken while the participant is in bed for the night to avoid orthostatic syncope, an uncommon but recognized "first dose" effect of prazosin or any alpha-1 antagonist if started at a high dose. The first dose effect is avoidable by starting treatment with a low dose (1 mg at bedtime) then titrating the dose upward gradually.	placebo: placebo titrated in the same manner as prazosin arm.	Total of all reporting groups
Overall Participants	32	35	67
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	30.0 (6.6)	30.8 (6.5)	30.4 (6.5)
Sex: Female, Male (Count of Participants)
Female	6 18.8%	4 11.4%	10 14.9%
Male	26 81.3%	31 88.6%	57 85.1%
Region of Enrollment (participants) [Number]
United States	32 100%	35 100%	67 100%

Outcome Measures

1. Primary Outcome

Title	Change in Clinician Administered PTSD Scale for DSM-IV (CAPS) Recurrent Distressing Dreams Item
Description	Item B-2 "recurrent distressing dreams of the event" is a single item from the Clinician Administered PTSD Scale. The rating consists of two parts: Frequency and Intensity. Symptom frequency rated 0 to 4. Symptom intensity rated 0 to 4. Frequency plus Intensity ratings equal the total score. A higher score is worse; a lower score is better. This outcome measure evaluates the change in score from Baseline to Week 15.
Time Frame	Baseline to Week 15

Outcome Measure Data

Analysis Population Description

Of the 67 subjects randomized, 46 completed the full 15 weeks (23 per group). The outcome data reports only those 46 participants who completed the full 15 weeks.

Arm/Group Title	Prazosin Hydrochloride	Placebo
Arm/Group Description	prazosin hydrochloride: Subject will be titrated up to the optimum tolerated dose based on the Dosing Algorithm. Males and females will be titrated differently with females titrated slower and to a lower maximum daily dose. The first dose will be taken while the participant is in bed for the night to avoid orthostatic syncope, an uncommon but recognized "first dose" effect of prazosin or any alpha-1 antagonist if started at a high dose. The first dose effect is avoidable by starting treatment with a low dose (1 mg at bedtime) then titrating the dose upward gradually.	placebo: placebo titrated in the same manner as prazosin arm.
Measure Participants	23	23
Mean (Standard Error) [Scores on a Scale]	3.1 (0.3)	1.2 (0.3)

2. Primary Outcome

Title	Change in Pittsburgh Sleep Quality Index (PSQI)
Description	Pittsburgh Sleep Quality Index is a self-report questionnaire assessing sleep quality and disturbances over a 1-month time interval. A global score is obtained by summing the seven component subscales (total score range: 0-21). A score of 5 or less indicates good sleep quality. A score of more than 5 indicates poor sleep quality. Change is measured from Baseline to Week 15.
Time Frame	Baseline to Week 15

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Prazosin Hydrochloride	Placebo
Arm/Group Description	prazosin hydrochloride: Subject will be titrated up to the optimum tolerated dose based on the Dosing Algorithm. Males and females will be titrated differently with females titrated slower and to a lower maximum daily dose. The first dose will be taken while the participant is in bed for the night to avoid orthostatic syncope, an uncommon but recognized "first dose" effect of prazosin or any alpha-1 antagonist if started at a high dose. The first dose effect is avoidable by starting treatment with a low dose (1 mg at bedtime) then titrating the dose upward gradually.	placebo: placebo titrated in the same manner as prazosin arm.
Measure Participants	23	23
Mean (Standard Error) [Scores on a Scale]	5.6 (0.7)	2.8 (0.6)

3. Primary Outcome

Title	Clinical Global Impression of Change (CGIC)
Description	The Clinical Global Impression of Change is a 7-point scale that rates global change compared to baseline (1=markedly improved, 2=moderately improved, 3=minimally improved, 4=no change, 5=minimally worse, 6=moderately worse, 7=markedly worse). The CGIC is used to determine the impact of treat effects on meaningful and distinct change in overall sense of well-being and functioning. This outcome measures the proportion of responders who were rated markedly or moderately improved at Week 15 compared to Baseline.
Time Frame	Change from Baseline to Week 15

Outcome Measure Data

Analysis Population Description

Of the 67 subjects randomized, 46 completed the full 15 weeks (23 per group). The outcome data reports only those 46 participants who completed the full 15 weeks.

Arm/Group Title	Prazosin Hydrochloride	Placebo
Arm/Group Description	prazosin hydrochloride: Subject will be titrated up to the optimum tolerated dose based on the Dosing Algorithm. Males and females will be titrated differently with females titrated slower and to a lower maximum daily dose. The first dose will be taken while the participant is in bed for the night to avoid orthostatic syncope, an uncommon but recognized "first dose" effect of prazosin or any alpha-1 antagonist if started at a high dose. The first dose effect is avoidable by starting treatment with a low dose (1 mg at bedtime) then titrating the dose upward gradually.	placebo: placebo titrated in the same manner as prazosin arm.
Measure Participants	23	23
Number (95% Confidence Interval) [Percentage of responders]	64	27

Adverse Events

Arm/Group Title	Prazosin Hydrochloride		Placebo
Arm/Group Description	prazosin hydrochloride: Subject will be titrated up to the optimum tolerated dose based on the Dosing Algorithm. Males and females will be titrated differently with females titrated slower and to a lower maximum daily dose. The first dose will be taken while the participant is in bed for the night to avoid orthostatic syncope, an uncommon but recognized "first dose" effect of prazosin or any alpha-1 antagonist if started at a high dose. The first dose effect is avoidable by starting treatment with a low dose (1 mg at bedtime) then titrating the dose upward gradually.		placebo: placebo titrated in the same manner as prazosin arm.
All Cause Mortality
	Prazosin Hydrochloride		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Prazosin Hydrochloride		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/32 (0%)		2/35 (5.7%)
Psychiatric disorders
Suicidal Ideation	0/32 (0%)	0	1/35 (2.9%)	1
Suicide attempt	0/32 (0%)	0	1/35 (2.9%)	1
Other (Not Including Serious) Adverse Events
	Prazosin Hydrochloride		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	18/32 (56.3%)		25/35 (71.4%)
Cardiac disorders
palpitations	3/32 (9.4%)	3	1/35 (2.9%)	1
Gastrointestinal disorders
nausea	5/32 (15.6%)	5	6/35 (17.1%)	7
General disorders
syncope	2/32 (6.3%)	2	0/35 (0%)	0
lack of energy	0/32 (0%)	0	1/35 (2.9%)	1
drowsiness	1/32 (3.1%)	1	3/35 (8.6%)	3
headache	1/32 (3.1%)	1	8/35 (22.9%)	8
dizziness	9/32 (28.1%)	10	7/35 (20%)	7
other	18/32 (56.3%)	35	25/35 (71.4%)	42
Musculoskeletal and connective tissue disorders
muscle weakness	2/32 (6.3%)	2	0/35 (0%)	0
Psychiatric disorders
depression	0/32 (0%)	0	2/35 (5.7%)	2
Respiratory, thoracic and mediastinal disorders
Nasal Congestion	7/32 (21.9%)	7	4/35 (11.4%)	4
Skin and subcutaneous tissue disorders
rash	1/32 (3.1%)	1	0/35 (0%)	0

Limitations/Caveats

The sample was restricted to soldiers with frequent recalled combat trauma nightmares. More studies in civilian trauma PTSD are needed. Results cannot be extrapolated to persons with PTSD who do not recall trauma nightmares.

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.