Prazosin for Alcohol Dependence and Posttraumatic Stress Disorder

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
VA Puget Sound Health Care System
Information provided by (Responsible Party):
Seattle Institute for Biomedical and Clinical Research
ClinicalTrials.gov Identifier:
NCT01518972
First received: January 23, 2012
Last updated: August 13, 2012
Last verified: August 2012
  Purpose

The purpose of this study is to determine whether the drug prazosin is effective for the treatment of alcohol dependency and symptoms of Posttraumatic Stress Disorder (PTSD).


Condition Intervention Phase
Alcohol Abuse
Posttraumatic Stress Disorder
Drug: Prazosin
Drug: Placebo medication
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Placebo-Controlled Trial of Prazosin in Individuals With Co-occurring Alcohol Dependence and PTSD Seeking Abstinence

Resource links provided by NLM:


Further study details as provided by Seattle Institute for Biomedical and Clinical Research:

Primary Outcome Measures:
  • Alcohol consumption and cravings [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • PTSD Symptoms [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 90
Study Start Date: September 2009
Estimated Study Completion Date: August 2012
Estimated Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Prazosin
Prazosin medication
Drug: Prazosin

Form: Prazosin will be taken orally, in the form of pills.

Dosing: 9 AM, 3 PM, 9 PM

Days 1-2: 0 mg, 0 mg, 1 mg

Days 3-4: 1 mg, 1 mg, 1 mg

Days 5-7: 2 mg, 2 mg, 2 mg

Day 8-10: 2 mg, 2 mg, 6 mg

Day 11-14: 4 mg, 4 mg, 6 mg

Day 15-84: 4 mg, 4 mg, 8 mg

Other Name: Minipress
Placebo Comparator: Placebo
Placebo medication
Drug: Placebo medication

Form: Placebo will be taken orally, in the form of pills.

Dosing: 9 AM, 3 PM, 9 PM

Days 1-2: 0 mg, 0 mg, 1 mg

Days 3-4: 1 mg, 1 mg, 1 mg

Days 5-7: 2 mg, 2 mg, 2 mg

Day 8-10: 2 mg, 2 mg, 6 mg

Day 11-14: 4 mg, 4 mg, 6 mg

Day 15-84: 4 mg, 4 mg, 8 mg


Detailed Description:

Background: Alcohol dependence (AD) is a biologically, genetically based disease, yet the majority of clinically accepted treatments are behaviorally or psychosocially based. PTSD and alcohol use disorders (AUDs) commonly co-occur. This comorbidity is associated with more severe clinical impairment, shorter times to relapse, more treatment recidivism, overall greater use of treatment services, and greater treatment costs.

Neuropharmacology of alcohol and prazosin: Emerging pre-clinical evidence shows that noradrenergic systems are involved in brain processes relevant to AD, such as arousal, reinforcement, and stress responsivity. However, virtually no work to date has attempted to translate this knowledge into clinically effective biological interventions. The investigators have adopted the novel, promising strategy of reducing adrenergic activity by blocking noradrenaline binding to post-synaptic alpha-1 receptors via the non-selective, alpha-1 antagonist, prazosin. Preclinical studies have demonstrated that prazosin decreases reinstatement of alcohol consumption, and preliminary clinical data suggest that prazosin reduces alcohol use in humans with AD and reduces PTSD-related nightmares and other symptoms, though it has not been tested in individuals with comorbid AD and PTSD. Prazosin, FDA approved to treat hypertension, typically has few side effects, and is inexpensive.

Design: Randomized double-blind placebo-controlled clinical trial. Participants: 60 individuals with both AD and PTSD (25% women) with stated goal to abstain from alcohol use.

Intervention: Either prazosin titrated per study protocol or matched placebo for 6 weeks with Medical Management (MM) based on the COMBINE Study procedures and a final study visit two weeks after medication discontinuation.

Measures: The primary outcomes are alcohol use during the 12-week medication phase of the study and reports of craving during the same time period. Daily, prompted Interactive Voice Response (IVR) telephone monitoring will be done throughout the 8-week study to assess the primary outcomes and to provide information on affect and medication adherence. Such daily monitoring provides more accurate reports of alcohol use than standard retrospective outcome measures. Analyses: Hierarchical linear modeling to test for main effects of prazosin+MM versus placebo+MM on alcohol use and PTSD symptoms over time, and to evaluate whether reductions in PTSD mediate the effect of prazosin.

Findings to date: The investigators have enrolled 30 participants and the 19 who met all the initial screening criteria were randomized overall. Since the last continuing review the investigators have enrolled 24 and randomized 15. Of the 24 participants enrolled, five are veterans and four of these has been randomized. Since the last continuing review, there have been two serious adverse events . In each case the institutional review board (IRB) review determined they were probably unrelated to the study. Enrollment continues.

Public health implications: There is a paucity of safe, tolerable, inexpensive, and efficacious drugs currently available for the treatment of AD and PTSD. Should the investigators find that prazosin leads to reduced alcohol use and PTSD symptom severity relative to placebo, clinicians will have an additional tool to help people with PTSD who are dependent on alcohol to make crucial changes in their lives.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Current primary DSM-IV diagnosis of alcohol dependence(AD)
  • Current DSM-IV diagnosis of PTSD
  • Heavy drinking in the last 30 days
  • At least 18 years of age
  • Good general medical health (see Exclusion Criteria below)
  • Capacity to provide informed consent
  • English fluency

Exclusion Criteria:

Psychiatric/behavioral:

  • psychiatric disorder requiring any medication other than anti-depressants
  • currently taking disulfiram, acamprosate, or naltrexone or planning to take any of these medications during the 12-week medication phase of the study
  • current dependence on any other psychoactive substance other than nicotine or cannabis
  • a current diagnosis of opioid abuse, use of any opioid- containing medications or benzodiazepines during the previous month, or UDA positive for opioids, benzodiazepines, or sedative hypnotics

Medical:

  • significant acute or chronic medical illness; women who are pregnant, nursing infant(s), or of childbearing potential and not using a contraceptive method judged by the study physician or PA to be effective
  • signs or symptoms of alcohol withdrawal at the time of initial consent
  • legal involvement that could interfere with study treatment
  • individuals court ordered for treatment will not be eligible to participate in this study
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01518972

Locations
United States, Washington
VA Puget Sound Health Care System
Seattle, Washington, United States, 98108
Sponsors and Collaborators
Seattle Institute for Biomedical and Clinical Research
VA Puget Sound Health Care System
Investigators
Principal Investigator: Tracy Simpson, PhD VA Puget Sound Health Care System
  More Information

No publications provided

Responsible Party: Seattle Institute for Biomedical and Clinical Research
ClinicalTrials.gov Identifier: NCT01518972     History of Changes
Other Study ID Numbers: P20 AA 017839
Study First Received: January 23, 2012
Last Updated: August 13, 2012
Health Authority: United States: Federal Government
United States: Institutional Review Board

Keywords provided by Seattle Institute for Biomedical and Clinical Research:
Alcohol
Abuse
Use
Disorder
Dependence
Symptoms
Alcoholic
Alcoholism
Prazosin
Drug
Medicine
Medication
Treatment
Study
Placebo
Medical
Management
Craving
Consumption
Binge
Drinking
Drink
Heavy
PTSD
Trauma
Post
Posttraumatic

Additional relevant MeSH terms:
Alcoholism
Stress Disorders, Post-Traumatic
Stress Disorders, Traumatic
Alcohol-Related Disorders
Substance-Related Disorders
Mental Disorders
Anxiety Disorders
Prazosin
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Adrenergic alpha-1 Receptor Antagonists
Adrenergic alpha-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 26, 2014