Prazosin to Reduce Stress-Induced Alcohol/Drug Craving and Relapse

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

100 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-09-30

Study Completion Date

2019-05-13

Brief Summary

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To test the preliminary efficacy of 16.0 mg of Prazosin daily versus placebo in treatment seeking alcohol dependent individuals. This proposal is a laboratory and treatment outcome study to examine the effects of Prazosin on brief exposure to stress, drug cues and neutral situations on alcohol and drug craving, mood and neurobiological reactivity in a sample of cocaine and/or alcohol dependent individuals. Prazosin will be beneficial for reduction in stress and alcohol cue induced craving and related arousal. In a sample of treatment-seeking alcohol dependent men and women, we propose to examine (a) differences in measures of alcohol craving, emotion state, hypothalamic-pituitary-adrenal (HPA) activation, physiological arousal and plasma catecholamine response to stress imagery and to alcohol cue imagery as compared to neutral imagery; (b) reduction in alcohol abstinence symptoms; and (c) improvement in alcohol treatment outcomes as measured by reductions in heavy drinking days, any drinking days, secondarily on drinks/day, anxiety, mood and sleep.

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Detailed Description

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This is a proof-of-concept (POC) experimental therapeutics study with 2 arms. The first is a double-blind placebo controlled laboratory study with 40 individuals meeting current alcohol dependence criteria (DSM-IVTR) who are admitted to the Clinical Neuroscience Research Unit and initiated on Prazosin vs Placebo (16mg/day) after admission and initial detoxification (if required). Experimental laboratory sessions are conducted after subjects achieved full dose after the 2-week titration, in week 3-4 of inpatient stay. The laboratory outcomes included alcohol craving, anxiety, negative affect and neuroendocrine and sympathetic arousal measures. Individuals who wished to remain on study medication for the outpatient (Arm 2) were maintained on study medication throughout the outpatient phase for a total period of 12 weeks.

Arm 2 of the POC study is a 12-week randomized clinical trial (RCT) of Prazosin (16mg/day) versus Placebo in 100 treatment seeking alcohol dependent individuals, to assess whether high anxiety and distress, including alcohol craving, manifest as increased alcohol withdrawal symptoms at treatment entry moderates Prazosin effects on alcohol use outcomes. Primary alcohol use outcomes include heavy drinking days, any drinking days and secondarily drinks/day. Additional secondary outcomes include alcohol craving, anxiety and mood symptoms and sleep disturbances. Patients from Arm 1 who wished to continue on study medication for the outpatient phase were included in Arm 2. Arm 2 patients were initiated on study medication upon presenting with a negative breathalyzer without any minimum pre-treatment alcohol abstinence period prior to medication initiation.

Conditions

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Alcohol Dependence

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Interaction effects of Alcohol withdrawal distress with Prazosin versus Placebo effects during the trial.

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Randomization into Prazosin/Placebo treatment was conducted by the Yale Stress Center biostatistician using an Urn randomization procedure that balanced groups on gender, age, nicotine smoking status, education years and lifetime history of DSM-IVTR anxiety disorders, including Post Traumatic Stress Disorder (PTSD). Random assignment of each patient was provided to the Yale Investigational Drug Service (IDS) Pharmacist, who formulated identical, matched tablets of Prazosin and Placebo, and provided dosing in weekly blister packs labeled by day and time of dosing for each subject to study staff for dispensing. All study personnel, including investigators, physicians, study staff and patients remained blind to medication group.

Study Groups

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High Alcohol Withdrawal on Prazosin

High AW was determined by those scoring at or above the median on Clinical Institute of Withdrawal for Alcohol Revised (CIWA-Ar) assessment. High AW were randomized to Prazosin 16 mg/day (tid) administered for 12 weeks with fish-bowl contingency management for weekly treatment attendance and manualized 12-Step relapse prevention counseling in a double blind manner.

Group Type ACTIVE_COMPARATOR

Prazosin Tablet

Intervention Type DRUG

Target medication dosing was three times/day (t.i.d. dosing) with 5 mg in the morning, 5 mg in the afternoon and 6 mg at night reached at the end of the 2-week period, and maintained at this or their highest tolerated dose until week 11, followed by a 5-day taper in week 12, as in previous research.The titration schedule was as follows: 1 mg dose at bedtime for 2 nights, followed by a 1mg dose morning and night (8 AM/8 PM) on day 3, then 2 mg dose t.i.d., on days 4-6, 3 mg dose (2 pills each) morning and afternoon, and 4 mg dose (2 pills) at night for days 7-9, increased to 4 mg dosing t.i.d. on days 10-13, and from day 14 through week 11, 5 mg (1 pill) each in the morning and afternoon, and 6 mg for the night (2 pills) dose. This was followed by a 5-day taper in week 12. Patients were initiated on study medication upon presenting with a negative breathalyzer without any minimum pre-treatment alcohol abstinence period prior to medication initiation.

High Alcohol Withdrawal on PLA

High AW was determined by those scoring at or above the median on Clinical Institute of Withdrawal for Alcohol Revised (CIWA-Ar) assessment. High AW were randomized to Placebo tablets administered tid for 12 weeks with fish-bowl contingency management for weekly treatment attendance and manualized 12-Step relapse prevention counseling in a double blind manner.

Group Type PLACEBO_COMPARATOR

Placebo Tablet

Intervention Type DRUG

Placebo tablets identical in appearance and dosing schedule as the active study medication was utilized

Low Alcohol Withdrawal on Prazosin

Low AW was determined by those scoring below the median on Clinical Institute of Withdrawal for Alcohol Revised (CIWA-Ar) assessment. Low AW were randomized to Prazosin 16 mg/day (tid) administered for 12 weeks with fish-bowl contingency management for weekly treatment attendance and manualized 12-Step relapse prevention counseling in a double blind manner.

Group Type ACTIVE_COMPARATOR

Prazosin Tablet

Intervention Type DRUG

Target medication dosing was three times/day (t.i.d. dosing) with 5 mg in the morning, 5 mg in the afternoon and 6 mg at night reached at the end of the 2-week period, and maintained at this or their highest tolerated dose until week 11, followed by a 5-day taper in week 12, as in previous research.The titration schedule was as follows: 1 mg dose at bedtime for 2 nights, followed by a 1mg dose morning and night (8 AM/8 PM) on day 3, then 2 mg dose t.i.d., on days 4-6, 3 mg dose (2 pills each) morning and afternoon, and 4 mg dose (2 pills) at night for days 7-9, increased to 4 mg dosing t.i.d. on days 10-13, and from day 14 through week 11, 5 mg (1 pill) each in the morning and afternoon, and 6 mg for the night (2 pills) dose. This was followed by a 5-day taper in week 12. Patients were initiated on study medication upon presenting with a negative breathalyzer without any minimum pre-treatment alcohol abstinence period prior to medication initiation.

Low Alcohol Withdrawal on PLA

Low AW was determined by those scoring below the median on Clinical Institute of Withdrawal for Alcohol Revised (CIWA-Ar) assessment.Placebo tablets administered tid for 12 weeks with fish-bowl contingency management for weekly treatment attendance and manualized 12-Step relapse prevention counseling in a double blind manner.

Group Type PLACEBO_COMPARATOR

Placebo Tablet

Intervention Type DRUG

Placebo tablets identical in appearance and dosing schedule as the active study medication was utilized

Interventions

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Prazosin Tablet

Target medication dosing was three times/day (t.i.d. dosing) with 5 mg in the morning, 5 mg in the afternoon and 6 mg at night reached at the end of the 2-week period, and maintained at this or their highest tolerated dose until week 11, followed by a 5-day taper in week 12, as in previous research.The titration schedule was as follows: 1 mg dose at bedtime for 2 nights, followed by a 1mg dose morning and night (8 AM/8 PM) on day 3, then 2 mg dose t.i.d., on days 4-6, 3 mg dose (2 pills each) morning and afternoon, and 4 mg dose (2 pills) at night for days 7-9, increased to 4 mg dosing t.i.d. on days 10-13, and from day 14 through week 11, 5 mg (1 pill) each in the morning and afternoon, and 6 mg for the night (2 pills) dose. This was followed by a 5-day taper in week 12. Patients were initiated on study medication upon presenting with a negative breathalyzer without any minimum pre-treatment alcohol abstinence period prior to medication initiation.

Intervention Type DRUG

Placebo Tablet

Placebo tablets identical in appearance and dosing schedule as the active study medication was utilized

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Male or female individuals, ages 18-70 with alcohol dependence, treatment seeking with varying levels of alcohol withdrawal symptoms.
* meet current DSM-IV criteria for alcohol dependence,
* Subject has voluntarily given informed consent and signed the informed consent document.
* Able to read English and complete study evaluations.

Exclusion Criteria

* Meet current criteria for dependence on another psychoactive substance, excluding nicotine and caffeine;
* Any current use of opiates;
* Current use of any psychoactive drugs, including anxiolytics, antidepressants, naltrexone or disulfram, except for stabilized on SSRIs
* Any psychotic disorder or current Axis I psychiatric symptoms requiring specific attention, including need for psychiatric medications for current major depression and anxiety disorders
* Significant underlying medical conditions such as cerebral, renal, thyroid or cardiac pathology which in the opinion of study physician would preclude patient from fully cooperating or be of potential harm during the course of the study;
* Hypotensive individuals with sitting blood pressure below 90/60 mmHG.

Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No