Clinical trial NCT04793685: Prazosin for Alcohol Use Disorder With Withdrawal Symptoms
Official title: Prazosin Treatment for Alcohol Use Disorder With Alcohol Withdrawal Symptoms
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Alcohol Withdrawal
Lead sponsor: Yale University
Sponsor class: OTHER
Collaborators: name: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
First posted: 2021-03-11
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Patients randomized to Prazosin 16 mg/day titrated over 2 weeks versus placebo taken for 12 weeks with week 12 taper of study medications.
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: In this Phase 2 single site RCT, individuals with moderate to severe alcohol use disorder (AUD) and presenc eof alcohol withdrawal symptoms (greater than 3 symptoms or more) will be enrolled in a 12 week trial with a 1- and 3- month follow up assessment. Subjects will be randomized to 16 mh /day Prazosin (PR) or Placebo (PBO) with a 2 week titration period and week 12 taper. All subjects will be assessed 2X weekly and also provided weekly behavioral counseling to support recovery.

Eligibility criteria: Inclusion Criteria:

* Alcohol Withdrawal (AW) scores of 3 or more on the CIWA-Ar at treatment entry and regular weekly use of alcohol at least 3X weekly or more at treatment entry;
* Must meet current DSM-5 criteria for moderate to severe Alcohol Use Disorder (AUD) using SCID-I for DSM-5;
* No health conditions that would impact trial participation as verified by screening and physical examination;
* Able to read English and complete study evaluations
* Able to provide informed written and verbal consent.

Exclusion Criteria:

* Meet current criteria for moderate to severe substance use disorders from use of any another psychoactive substance, excluding nicotine;
* Current use of opioids or past history of opioid use disorder;
* Regular use of anticonvulsants, sedatives/hypnotics, oral prescription analgesics (other than noon-steroidal antiinflammatory drugs), other antihypertensives, anti-arrythmics, antiretroviral medications, tricyclic antidepressants, acamprosate, naltrexone, antabuse, topiramate, gabapentin, baclofen, varenicline;
* Psychotic or otherwise severely psychiatrically disabled (i.e., suicidal, homicidal, current mania);
* 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;
* Any psychotic disorder or current Axis I psychiatric disorders requiring specific attention, including need for psychiatric medications;
* Hypotensive individuals with sitting blood pressure below 100/50 mmHG;
* 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).

Primary outcomes:
measure: Percent of Subjects with no Heavy Drinking Days
timeFrame: up to 12 weeks
Secondary outcomes:
measure: Percent Heavy Drinking Days
timeFrame: up to 12 weeks
measure: Percent Any Drinking Days
timeFrame: up to 12 weeks
measure: Average Drinks per Day
timeFrame: up to 12 weeks
Other outcomes:
Locations:
city: New Haven
country: United States
facility: The Yale Stress Center: Yale University
state: Connecticut
city: New Haven
country: United States
facility: The Yale Stress Center: Yale University
state: Connecticut
Study officials:
affiliation: Yale University
name: David Fiellin, MD
role: STUDY_DIRECTOR
affiliation: Yale University
name: Gretchen Hermes, MD
role: STUDY_DIRECTOR
References:
citation: Sinha R, Wemm S, Fogelman N, Milivojevic V, Morgan PM, Angarita GA, Hermes G, Fox HC. Moderation of Prazosin's Efficacy by Alcohol Withdrawal Symptoms. Am J Psychiatry. 2021 May 1;178(5):447-458. doi: 10.1176/appi.ajp.2020.20050609. Epub 2020 Nov 19.