Clinical trial NCT01518972: Prazosin for Alcohol Dependence and Posttraumatic Stress Disorder
Official title: A Placebo-Controlled Trial of Prazosin in Individuals With Co-occurring Alcohol Dependence and PTSD Seeking Abstinence
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Alcohol Abuse
Posttraumatic Stress Disorder
Keywords: 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
Lead sponsor: Seattle Institute for Biomedical and Clinical Research
Sponsor class: OTHER
Collaborators: name: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
name: VA Puget Sound Health Care System
First posted: 2012-01-26
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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
* 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 (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

Primary outcomes:
measure: Percent Drinking Days Per Week
timeFrame: 6 weeks
measure: Percent Heavy Drinking Days Per Week
timeFrame: 6 weeks
measure: Total Drinks Per Week
timeFrame: 6 weeks
Secondary outcomes:
measure: PTSD Symptom Assessments
timeFrame: 6 weeks
Other outcomes:
Locations:
city: Seattle
country: United States
facility: VA Puget Sound Health Care System
state: Washington
Study officials:
affiliation: VA Puget Sound Health Care System
name: Tracy L Simpson, PhD
role: PRINCIPAL_INVESTIGATOR
References: