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

Alcohol Dependence Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00585780
• Other study ID #: 0705002691
• Secondary ID: 4R01AA020504-05
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: September 2009
• Est. completion date: May 13, 2019

Study information

• Verified date: July 2020
• Source: Yale University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 100
• Est. completion date: May 13, 2019
• Est. primary completion date: August 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Alcohol Dependence
• Alcoholism

Intervention

Drug:
• 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.
• Placebo Tablet
Placebo tablets identical in appearance and dosing schedule as the active study medication was utilized

Locations

Country	Name	City	State
United States	Yale University School of Medicine: Yale Stress Center	New Haven	Connecticut

Sponsors (3)

Lead Sponsor	Collaborator
Yale University	National Institute on Alcohol Abuse and Alcoholism (NIAAA), National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Heavy Drinking Days (HDD%) During the Full Dose Period From Weeks 3-12	Percentage of heavy drinking days (HDD%) during the full dose period from weeks 3-12 where heavy drinking day (HDD) is defined as 5 or more for men and 4 or more for women in one sitting, measured as yes (1) or no(0), assessed via self reports by daily surveys and time-line follow back assessments	daily over 12 weeks
Primary	Percent of Drinkings Days During the Full Dose Period Between Weeks 3 and 12	Percent of any drinkings days over the full dose period from weeks 3 to 12, defined as any alcoholic drink consumed each day measured as yes (1) or no(0), assessed via self reports by daily surveys and time-line follow back assessments	daily over 12 weeks