Prazosin for Alcohol Withdrawal
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Yale University
Must not be taking: Opioids, Anticonvulsants, Antidepressants, others
Disqualifiers: Substance use disorders, Psychotic disorders, others
Prior Safety Data
Approved in 1 Jurisdiction
Trial Summary
What is the purpose of this trial?This is a Phase 2 single site randomized clinical trial (RCT) to be supported by a new NIH-NIAAA grant, R01-AA029113-01, to assess the efficacy of Prazosin (16mg/day) versus Placebo over a 12 week treatment period, followed by a 1- and 3- month assessments post-treatment for individuals with Alcohol Use Disorder (AUD) and history of past or current evidence of alcohol withdrawal symptoms. If medical detoxification is required for any patient, patients would be enrolled after medical detoxification. for those not requiring detoxification, they will be enrolled directly without any requirement of alcohol abstinence. All patients will be provided behavioral counseling weekly with a trained counselor to support recovery during the trial. Primary outcomes will be percent of subjects no heavy drinking days (PSNHDD) and %of any drinking and heavy drinking days as well as secondary outcomes of craving, mood, anxiety and sleep problems.
Will I have to stop taking my current medications?
Yes, you will need to stop taking certain medications. The trial excludes people who regularly use anticonvulsants, sedatives, certain pain relievers, and other specific medications. It's important to discuss your current medications with the trial team to see if you qualify.
What data supports the effectiveness of the drug Prazosin for alcohol withdrawal?
Research suggests that Prazosin may help reduce alcohol intake and prevent relapse in people with high alcohol withdrawal symptoms. In a study, Prazosin reduced drinking days and heavy drinking days in patients with significant withdrawal symptoms, and animal studies showed it decreased alcohol consumption in rats.
12345Is prazosin safe for use in humans?
Prazosin is generally considered safe for use in humans, but it can lower blood pressure, especially when combined with alcohol, which may cause dizziness or fainting. It is important to monitor blood pressure and discuss any concerns with a healthcare provider.
15678How does the drug prazosin differ from other treatments for alcohol withdrawal?
Prazosin is unique because it targets adrenergic mechanisms (related to the nervous system's response to stress) to reduce alcohol withdrawal symptoms, which may help prevent relapse in people with alcohol use disorder. Unlike some other treatments, prazosin's effectiveness is particularly noted in patients with high alcohol withdrawal symptoms.
12357Eligibility Criteria
This trial is for individuals with moderate to severe Alcohol Use Disorder who experience withdrawal symptoms. Participants must be able to read English, have no other substance use disorders (except nicotine), and not be using certain medications like opioids or antihypertensives. They should not have severe psychiatric conditions or significant medical issues that could interfere with the study.Inclusion Criteria
Must meet current DSM-5 criteria for moderate to severe Alcohol Use Disorder (AUD) using SCID-I for DSM-5;
Able to read English and complete study evaluations
Able to provide informed written and verbal consent
+6 more
Exclusion Criteria
I do not have a severe mental health condition that needs specific treatment or medication.
Meet current criteria for moderate to severe substance use disorders from use of any another psychoactive substance, excluding nicotine
Women who are pregnant, nursing or refuse to use a reliable form of birth control (as assessed by pregnancy tests during initial medical evaluation, and assessed every two weeks during the course of the study)
+5 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive Prazosin or Placebo over a 12-week period with a 2-week titration and a 5-day taper, along with weekly behavioral counseling
12 weeks
2 visits per week (in-person)
Follow-up
Participants are monitored for safety and effectiveness after treatment with assessments at 1 and 3 months post-treatment
3 months
2 visits (in-person)
Participant Groups
The trial tests Prazosin (16mg/day) against a placebo over 12 weeks in patients with Alcohol Use Disorder and withdrawal symptoms. It includes weekly behavioral counseling sessions. The main focus is on reducing heavy drinking days, along with monitoring craving, mood, anxiety, and sleep problems.
2Treatment groups
Experimental Treatment
Placebo Group
Group I: Active DrugExperimental Treatment2 Interventions
Prazosin (16mg/day) versus Placebo comparator, administered in t.i.d schedule, in capsules, over a 12 week period, with 2 weeks titration in weeks 1-2 and a 5-day taper in week 12.
Group II: Placebo DrugPlacebo Group1 Intervention
Placebo for 12 weeks.
Prazosin is already approved in United States for the following indications:
🇺🇸 Approved in United States as Minipress for:
- Hypertension
- Benign prostatic hypertrophy
- Posttraumatic stress disorder (PTSD) nightmares and hyperarousal symptoms
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
The Yale Stress Center: Yale UniversityNew Haven, CT
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Who Is Running the Clinical Trial?
Yale UniversityLead Sponsor
National Institute on Alcohol Abuse and Alcoholism (NIAAA)Collaborator
References
Moderation of Prazosin's Efficacy by Alcohol Withdrawal Symptoms. [2022]Alcohol use disorder (AUD) is a leading cause of global disease burden. Chronic, heavy use increases the likelihood of alcohol withdrawal symptoms and associated secondary outcomes of alcohol craving and mood, anxiety, and sleep disturbances, which are predictive of poor treatment outcomes. The authors examined whether alcohol withdrawal symptoms moderate the efficacy of prazosin in reducing alcohol intake and associated secondary outcomes.
Prazosin for Alcohol Use Disorder: A Symptom-Driven Approach to the Choice of Intervention. [2021]The choice from among approved treatments for relapse prevention in alcohol use disorder (AUD) is not symptom-driven. It is reasonable to speculate that the discomfort and distress associated with the experience of alcohol withdrawal symptoms (AWS) discourage abstinence and prompt continuation of or relapse into drinking. Adrenergic mechanisms may underlie many of the commonly experienced AWS. This allows the further speculation that drugs with antiadrenergic properties may attenuate AWS and thereby improve treatment outcomes in patients with AUD who attempt to quit drinking. In this context, the α1 adrenoceptor antagonist prazosin is a possible symptom-driven choice for patients with AUD who experience high AWS. Randomized controlled trial (RCT) results with prazosin and doxazosin have however been mixed, perhaps because the role of AWS was not considered in these. In this context, a recent large (n = 100) RCT found that prazosin, uptitrated to 16 mg/d, reduced drinking days, heavy drinking days, and average drinks per day; the benefits were observed only in patients with high AWS at baseline, operationalized as a Clinical Institute Withdrawal Assessment for Alcohol-Revised score of 3 or higher. Concerns about the internal and external validity of this study are discussed. How and when high AWS is determined is also a point of debate. If high AWS is a valid target for the symptom-driven choice of pharmacologic intervention for AUD, then a wide range of drugs merits study; in the long run, some of these drugs may be better tolerated than prazosin.
Prazosin Reduces Alcohol Intake in an Animal Model of Alcohol Relapse. [2019]Many alcoholics and heavy drinkers undergo repeated cycles of alcohol abstinence followed by relapse to alcohol drinking; a pattern that contributes to escalated alcohol intake over time. In rodents, alcohol drinking that is interspersed with periods of alcohol deprivation (imposed abstinence) increases alcohol intake during reaccess to alcohol. This is termed the "alcohol deprivation effect" or "ADE" and is a model of alcohol relapse in humans. We have previously reported that prazosin reduces alcohol drinking during both brief and prolonged treatment in rats selectively bred for alcohol preference ("P" rats). This study explores whether prazosin prevents alcohol "relapse" in P rats, as reflected by a reduced or abolished ADE.
Effects of prazosin, an α1-adrenergic receptor antagonist, on the seeking and intake of alcohol and sucrose in alcohol-preferring (P) rats. [2021]Previous studies show that prazosin, an α(1) -adrenergic receptor antagonist, decreases alcohol drinking in animal models of alcohol use and dependence [Rasmussen et al. (2009) Alcohol Clin Exp Res 3:264-272; Walker et al. (2008) Alcohol 42:91-97] and in alcohol-dependent men [Simpson et al. (2009) Alcohol Clin Exp Res 33:255-263]. This study extended these findings by using a paradigm that allows for separate assessment of prazosin on motivation to seek versus consume alcohol or sucrose in selectively bred rats.
Interaction of alcohol and an alpha1-blocker on ambulatory blood pressure in patients with essential hypertension. [2019]Ingestion of alcohol acutely decreases vascular resistance and blood pressure (BP) with activation of the sympathetic nervous system in Orientals. Although alpha1-blockers are widely used in the treatment of hypertension, the possible interaction between alcohol and alpha1-blockers has not been clarified. We examined the effects of prazosin on the alcohol-induced BP changes in Japanese men with mild hypertension. Ten hypertensive patients (54 +/- 3 years, mean +/- SE) were given 1 mL/kg of alcohol or isocaloric control drink with a light meal in the evening before and 5 to 7 days after treatment with prazosin (1 mg three times daily). Ambulatory BP monitoring was carried out every 30 min for 24 h in each period using Colin ABPM-630. Blood samples were obtained before and 2 h after intake of alcohol or control drink. Before prazosin treatment, alcohol ingestion decreased BP for several hours with a significant reduction in average 24-h BP, whereas it increased heart rate, plasma norepinephrine, and plasma renin activity. Treatment with prazosin caused a significant decrease in 24-h BP (136.3 +/- 4.0/82.8 +/- 2.5 v 131.6 +/- 3.2/80.0 +/- 2.3 mm Hg). The alcohol-induced hypotension at 2-4 h after ingestion was enhanced by prazosin (-18.0 +/- 3.7/-11.8 +/- 2.7 v -24.4 +/- 4.9/-17.8 +/- 2.8 mm Hg, P
A case of alcohol withdrawal requiring 1,600 mg of lorazepam in 24 hours. [2019]Alcohol withdrawal continues to present significant morbidity and mortality in hospitalized medical/surgical patients. The authors present a case of a patient with delirium tremens requiring up to 1,600 mg/day of lorazepam and discuss alternative treatments for alcohol withdrawal.
Use of injectable lorazepam in alcohol withdrawal. [2021]Lorazepam, a new minor benzodiazepine tranquillizer, was given intramuscularly to 19 patients suffering from acute alcohol withdrawal. The severity of their symptoms decreased rapidly. Lorazepam appears to be useful in the management of withdrawal symptoms, and more extensive trials are recommended.
Clonidine in alcohol withdrawal. [2019]In a doubl-blind study, patients receiving a rapidly falling dosage of clonidine recovered about 1 day faster from the symptoms of moderately severe alcohol withdrawal than patients receiving placebo. The effects of clonidine were especially noticeable with respect to tremor, sweating, elevated systolic blood pressure, tension, anxiety, depression, and general condition. Clonidine had no effect on the sleep disturbances. No significant side effects were seen. It is suggested that clonidine is a useful aid in the treatment of alcohol withdrawal, especially when it is desirable to minimise the use of tranquillisers.