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

NCT00585780 | Completed Phase 1 Results DMC

• 2 other identifiers: 07050026914R01AA020504-05
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Alcohol Dependence

Outcome Measures

Primary Outcomes (2)

• 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

• 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

Study Arms (4)

High Alcohol Withdrawal on Prazosin

ACTIVE COMPARATOR

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.

Drug: Prazosin Tablet

High Alcohol Withdrawal on PLA

PLACEBO COMPARATOR

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.

Drug: Placebo Tablet

Low Alcohol Withdrawal on Prazosin

ACTIVE COMPARATOR

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.

Drug: Prazosin Tablet

Low Alcohol Withdrawal on PLA

PLACEBO COMPARATOR

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.

Drug: Placebo Tablet

Interventions

Prazosin Tablet 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 Prazosin; Low Alcohol Withdrawal on Prazosin

Placebo Tablet DRUG

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

High Alcohol Withdrawal on PLA; Low Alcohol Withdrawal on PLA

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Yale University: lead
• National Institutes of Health (NIH): collaborator
• National Institute on Alcohol Abuse and Alcoholism (NIAAA): collaborator

Study Sites (1)

Yale University School of Medicine: Yale Stress Center

New Haven, Connecticut, 06519, United States

Location

MeSH Terms

Conditions

Alcoholism

Interventions

Prazosin

Condition Hierarchy (Ancestors)

Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Limitations and Caveats

There was not adequate power to assess sex differences, and specific sensitivity and specificity data for apriori AW cutoffs for Prazosin benefit in high AW group needs to be determined in future studies.

Results Point of Contact

• Title: Dr. Rajita Sinha
• Organization: YALE UNIVERSITY SCHOOL OF MEDICINE

rajita.sinha@yale.edu

2038592840

Study Officials

• Rajita Sinha, PhD

  Yale University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

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

Study Record Dates

• First Submitted: December 25, 2007
• First Posted: January 3, 2008
• Study Start: September 1, 2009
• Primary Completion: August 1, 2018
• Study Completion: May 13, 2019
• Last Updated: July 27, 2020
• Results First Posted: July 27, 2020

Record last verified: 2020-07

Locations

US (1)