Prazosin for Alcohol Dependence and Posttraumatic Stress Disorder

NCT ID: NCT01518972

Last Updated: 2020-08-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-09-30
• Study Completion Date: 2012-06-30

Brief Summary

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).

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: Participants randomized to prazosin had a greater reduction in percent days drinking per week and percent days heavy drinking per week between baseline and week 6 than did placebo participants. No significant differences were detected within or between groups in change from weeks 1 to 6 in total PTSD symptoms. Participants in the prazosin condition reported drowsiness on significantly more days than those in the placebo condition. Public health implications: There is a paucity of safe, tolerable, inexpensive, and efficacious drugs currently available for the treatment of AD and PTSD. Consistent with the extant research evaluating medications for comorbid PTSD/AD, the current evaluation of prazosin also found decreased alcohol consumption but no medication effect on PTSD symptomatology.

Conditions

Alcohol Abuse; Posttraumatic Stress Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Prazosin

Prazosin medication

Group Type: EXPERIMENTAL

Prazosin

Intervention Type: DRUG

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

Placebo

Placebo medication

Group Type: PLACEBO_COMPARATOR

Placebo medication

Intervention Type: DRUG

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

Interventions

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

Intervention Type: 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

Intervention Type: DRUG

Other Intervention Names

Minipress; Placebo

Eligibility Criteria

Inclusion Criteria

• Current primary DSM-IV diagnosis of alcohol dependence(AD)
• Current DSM-IV diagnosis of PTSD
• At least 14 (women) or 21 (men) drinks per week AND at least 2 days of heavy drinking during a consecutive 30 day period in the last 90 days
• Desire to abstain from drinking
• At least 18 years of age

Exclusion Criteria

• Capacity to provide informed consent
• English fluency

Psychiatric/behavioral:

• psychiatric disorder requiring any medication other than anti-depressants (individuals not on a stable dose of an anti-depressant for at least 30 days prior to randomization will be excluded from the study)
• currently taking disulfiram, acamprosate, or naltrexone in the last 30 days or planning to take any of these medications during the 12-week medication phase of the study
• acutely suicidal or homicidal
• current dependence on any other psychoactive substance other than nicotine or cannabis
• a current diagnosis of opioid abuse, use of any opioid- containing medications, methamphetamines, or benzodiazepines during the previous month, or UDA positive for opioids, methamphetamines, benzodiazepines, or sedative hypnotics

Medical:

• significant acute or chronic medical illness including unstable angina, recent myocardial infarction, history of congestive heart failure, preexisting hypotension (systolic <110) or orthostatic hypotension (defined as a systolic drop > 20mmHg after two minutes standing or any drop with dizziness); insulin-dependent diabetes mellitus; chronic renal or hepatic failure, pancreatitis, Meniere's disease, benign positional vertigo, narcolepsy
• for males only, concomitant use of trazodone (or use in the last 7 days), tadalafil, or vardenafil (or use in the last 3 days) due to increased risk of priapism
• history of prazosin-sensitivity; no prazosin for at least the past 30 days
• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

NIH

Sponsor Role: collaborator

VA Puget Sound Health Care System

FED

Sponsor Role: collaborator

Seattle Institute for Biomedical and Clinical Research

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Tracy L Simpson, PhD

Role: PRINCIPAL_INVESTIGATOR

VA Puget Sound Health Care System

Locations

VA Puget Sound Health Care System

Seattle, Washington, United States

Countries

United States

Provided Documents

Document Type: Informed Consent Form

View Document

Other Identifiers

1P20AA017839-01

Identifier Type: NIH

Identifier Source: secondary_id

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P20AA017839

Identifier Type: NIH

Identifier Source: org_study_id

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