Prazosin for Treatment of Patients With Alcohol Dependence (AD) and Post Traumatic Stress Disorder (PTSD).

• Sponsor: Yale University (Other)
• Overall Status: Completed
• CT.gov ID: NCT00744055
• Collaborator: (none)
• Enrollment: 96
• Location: 1
• Arms: 2
• Duration (Months): 69
• Patients Per Site Per Month: 1.4

Study Details

Study Description

Brief Summary

Prazosin is an alpha-1 adrenergic receptor antagonist that has been used successfully in the treatment of trauma nightmares and sleep disturbance in combat veterans with PTSD, and alcohol dependence.

The objective of this study is to evaluate the efficacy of prazosin (16mg) versus placebo in reducing alcohol consumption and decreasing symptoms of PTSD in patients with comorbid AD and PTSD.

Condition or Disease	Intervention/Treatment	Phase
Alcohol Dependence; Stress Disorders, Post-Traumatic	Drug: Prazosin; Drug: Placebo	Phase 3

Detailed Description

Background:

There is a high rate of comorbidity with alcohol dependence (AD) and post traumatic stress disorder (PTSD). The rates of PTSD among individuals with AD are at least twice as high as those in the general population. In addition, alcohol dependence is the most common comorbid condition in men with PTSD. Despite this, little is known about how to best treat individuals with comorbid AD and PTSD. The use of an alpha-1 adrenergic receptor antagonist represents a novel approach to treatment that may target symptoms of both AD and PTSD. There is evidence of common neurobiological mechanisms that underlie both AD and PTSD. Prazosin is an alpha-1 adrenergic receptor antagonist that has been used successfully in the treatment of trauma nightmares and sleep disturbance in combat veterans with PTSD, and alcohol dependence.

Objective:

The objective of this study is to evaluate the efficacy of prazosin (16mg) versus placebo in reducing alcohol consumption and decreasing symptoms of PTSD in patients with comorbid AD and PTSD. Methods: Thirty participants with a current diagnosis of AD and PTSD will be enrolled in a 13-week trial. They will be assigned, in a double-blind fashion, to either prazosin or placebo. Significance: This project will be the first to compare prazosin to placebo as effective treatments for reducing alcohol consumption and PTSD symptoms in patients with both AD and PTSD.

Study Design

• Study Type: Interventional
• Actual Enrollment: 96 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: The Use of Prazosin for Treatment of Patients With Alcohol Dependence (AD) and Post Traumatic Stress Disorder (PTSD).
• Study Start Date: Jan 1, 2009
• Actual Primary Completion Date: Oct 1, 2014
• Actual Study Completion Date: Oct 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Prazosin prazosin (16mg/day)	Drug: Prazosin; prazosin (16mg/day) 2 times a day; Other Names: Minipress
Placebo Comparator: Placebo Placebo in identical looking capsule blister packs	Drug: Placebo; Placebo

Outcome Measures

Primary Outcome Measures

1. Number of Drinking Days [12 weeks]

   Using the Timeline Follow Back method, a calendar method for assessing drug and alcohol use

2. Clinician-Administered PTSD Scale [12 weeks]

   Clinician-Administered PTSD Scale for DSM-5 (CAPS-5). A higher score is associated with higher severity of PTSD. The score is interpreted as follows: 0-19=Asymptomatic/few symptoms 20-39=Sub-threshold/mild PTSD 40-59=Threshold PTSD/moderate 60-79=Severe PTSD >80=Extreme PTSD

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Males and females between the ages of 21-65 years old.

2. Current alcohol dependence, as determined by a structured clinical interview (Structured Clinical Interview for DSM-IV Axis I Disorders) (SCID) (First et al. 1996).

3. Current PTSD as determined by the Clinician Administered PTSD Scale for DSM-IV(CAPS) (Blake et al. 1995).

4. Patients with current alcohol dependence, with at least one recent episode of heavy drinking (defined as 5 or more drinks per drinking episode) over the past 14 days.

5. Medically and neurologically healthy on the basis of history, physical examination, EKG, screening laboratories (CBC w/ differential, TSH, Free-T4, ASAT, ALAT, GGT, BUN, creatinine, calcium, phosphorous, magnesium, total protein, albumin, electrolytes, VDRL, urinalysis, beta-HCG).

6. For women, negative pregnancy test and use of acceptable method of contraception.

Exclusion Criteria:

1. Females who are pregnant or lactating.

2. Individuals with a current unstable medical condition such as neurological, cardiovascular, endocrine, renal, liver, or thyroid pathology (LFT 5 times normal, abnormal BUN and creatinine, and unmanaged hypertension with BP more than 200/120) which in the opinion of the physician would preclude the patient from fully cooperating or be of potential harm during the course of the study.

3. Patients who meet current SCID criteria for the following major Axis I diagnoses (Bipolar Disorders, Schizophrenia and Schizophrenia-type Disorders).

4. History of substance dependence (other than alcohol, cocaine, tobacco or cannabis) by DSM-IV criteria in the last 30 days.

5. Individuals taking mood stabilizers and antipsychotic medications.

6. Individuals with a history of sensitivity to quinazolines or prazosin.

7. Individuals taking medications thought to influence alcohol consumption (naltrexone, disulfiram, acamprosate).

8. Individuals taking adrenergic medication (e.g. clonidine).

9. Agents that may interact with prazosin such as drugs with CNS depressant effects including tizanidine and xyrem.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	VA Connecticut Healthcare System	West Haven	Connecticut	United States	06516

Sponsors and Collaborators

• Yale University

Investigators

• Principal Investigator: Ismene Petrakis, MD, Yale University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Yale University
• ClinicalTrials.gov Identifier: NCT00744055
• Other Study ID Numbers: 0801003450
• First Posted: Aug 29, 2008
• Last Update Posted: Mar 19, 2020
• Last Verified: Mar 1, 2020

• Keywords provided by Yale University: alcohol dependence; post traumatic stress disorder; treatment; prazosin
• Additional relevant MeSH terms: Disease; Alcoholism; Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic; Prazosin

Study Results

Participant Flow

Pre-assignment Detail	Randomization was conducted by the pharmacy using a 1:1 randomization in blocks of 4 and stratified by site, gender. Completers were defined as subjects for whom we had complete data at the end of the treatment period (week 12) whether they remained on medication or not.

Arm/Group Title	Prazosin	Placebo
Arm/Group Description	prazosin (16mg/day) Prazosin: prazosin (16mg/day) 2 times a day	Placebo in identical looking capsule blister packs Placebo: Placebo
Period Title: Overall Study
STARTED	50	46
COMPLETED	43	32
NOT COMPLETED	7	14

Baseline Characteristics

Arm/Group Title	Prazosin	Placebo	Total
Arm/Group Description	men or women, ages of 21-65, met DSM-IV criteria for current PTSD and alcohol dependence (AD) (determined by structured clinical interview)	men or women, ages of 21-65, met DSM-IV criteria for current PTSD and alcohol dependence (AD) (determined by structured clinical interview)	Total of all reporting groups
Overall Participants	50	46	96
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	44.5 (13.2)	43.40 (12.95)	43.96 (12.96)
Sex: Female, Male (Count of Participants)
Female	4 8%	2 4.3%	6 6.3%
Male	46 92%	44 95.7%	90 93.8%
Race/Ethnicity, Customized (participants) [Number]
Caucasian	40 80%	38 82.6%	78 81.3%
Non-Caucasian	10 20%	8 17.4%	18 18.8%
PTSD Symptoms (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	71.86 (20.32)	75.86 (14.44)	73.7 (17.86)
Average Drinks Per Drinking Day (drinks per day) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [drinks per day]	17.33 (10.73)	21.90 (13.24)	19.53 (8.21)

Outcome Measures

1. Primary Outcome

Title	Number of Drinking Days
Description	Using the Timeline Follow Back method, a calendar method for assessing drug and alcohol use
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Prazosin	Placebo
Arm/Group Description	prazosin (16mg/day) Prazosin: prazosin (16mg/day) 2 times a day	Placebo in identical looking capsule blister packs Placebo
Measure Participants	50	46
Mean (Standard Deviation) [days]	11.04 (18.86)	9.21 (16.64)

2. Primary Outcome

Title	Clinician-Administered PTSD Scale
Description	Clinician-Administered PTSD Scale for DSM-5 (CAPS-5). A higher score is associated with higher severity of PTSD. The score is interpreted as follows: 0-19=Asymptomatic/few symptoms 20-39=Sub-threshold/mild PTSD 40-59=Threshold PTSD/moderate 60-79=Severe PTSD >80=Extreme PTSD
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Prazosin	Placebo
Arm/Group Description	prazosin (16mg/day) Prazosin: prazosin (16mg/day) 2 times a day	Placebo in identical looking capsule blister packs Placebo
Measure Participants	50	46
Mean (Standard Deviation) [units on a scale]	37.94 (37.62)	37.93 (41.13)

Adverse Events

Time Frame	12 weeks
Arm/Group Title	Prazosin		Placebo
Arm/Group Description	prazosin (16mg/day) Prazosin: prazosin (16mg/day) 2 times a day		Placebo in identical looking capsule blister packs Placebo
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	0/50 (0%)		0/46 (0%)
Other (Not Including Serious) Adverse Events
	Prazosin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/50 (22%)		8/46 (17.4%)
Gastrointestinal disorders
Appendicitis	1/50 (2%)		0/46 (0%)
General disorders
Fainting	1/50 (2%)		0/46 (0%)
Falling	2/50 (4%)		0/46 (0%)
Psychiatric disorders
Alcohol Relapse	5/50 (10%)		7/46 (15.2%)
Homocidal Ideation	0/50 (0%)		1/46 (2.2%)
Respiratory, thoracic and mediastinal disorders
Chest Pain	1/50 (2%)		0/46 (0%)
Vascular disorders
Partial thrombus	1/50 (2%)		0/46 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE 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.