Clinical trial NCT04135846: Alpha-1 Blockade for Alcohol Use Disorder (AUD)
Official title: A Focus on Alpha-1 Blockade as a Novel Pharmacological Treatment for AUD
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Alcohol Use Disorder (AUD)
Keywords: Alcohol use disorder, stress
Lead sponsor: Brown University
Sponsor class: OTHER
First posted: 2019-10-23
Enrollment: 184
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The goal of this research is to replicate findings previously conducted in a pilot trial and to understand, mechanistically, the role of stress in the development of AUD pharmacotherapies that target noradrenergic blockade.

Detailed description: 16 week, between-subject, double-blind, randomized clinical trial (RCT) with doxazosin (16 mg, or maximum tolerated dose, MTD) compared to placebo in 184 treatment seeking individuals with AUD

Eligibility criteria: Inclusion Criteria:

* Male or female, 18 years of age
* Meet the DSM-5 criteria for AUD
* Desire to reduce or quit alcohol drinking
* Breath alcohol (BrAC) = 0.00 at each visit
* In good health as confirmed by medical history, physical examination and lab tests
* Willing to adhere to the study procedures
* Understand informed consent and questionnaires in English at an 8th grade level

Exclusion Criteria:

* Women who are breastfeeding or /positive urine test for pregnancy
* CrCl\<60mL/min
* Suicide attempt in the last three months
* Current diagnosis of other substance disorder other than nicotine as assessed by self-report and urine toxicology screen at baseline
* Current use of medication that may interact with doxazosin and/or yohimbine
* History of allergy to any alpha receptor blockers
* Clinical Institute Withdrawal Assessment for Alcohol revised (CIWA-Ar) score ≥ 8
* Treatment with disulfiram, naltrexone, acamprosate, topiramate within 1 month prior to screening
* Treatment with any alpha-blocker
* Individuals with cardiac heat failure (CHF), as assessed by the medical history, the physical exam and the ECG.
* Baseline hypotension defined as BP reading lower than 90/60 mmHg
* Use of phosphodiesterase inhibitors (PDE5) erectile dysfunction medication

Primary outcomes:
measure: Alcohol consumption
timeFrame: 6 weeks
Secondary outcomes:
measure: Alcohol craving
timeFrame: one day
measure: Alcohol craving
timeFrame: six weeks
Other outcomes:
Locations:
city: Providence
country: United States
facility: Brown University
state: Rhode Island
Study officials:
affiliation: Brown University
name: Carolina L Haass-Koffler, PHARMD, PHD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Haass-Koffler CL, Goodyear K, Zywiak WH, Magill M, Eltinge SE, Wallace PM, Long VM, Jayaram-Lindstrom N, Swift RM, Kenna GA, Leggio L. Higher pretreatment blood pressure is associated with greater alcohol drinking reduction in alcohol-dependent individuals treated with doxazosin. Drug Alcohol Depend. 2017 Aug 1;177:23-28. doi: 10.1016/j.drugalcdep.2017.03.016. Epub 2017 May 16.
citation: Kenna GA, Haass-Koffler CL, Zywiak WH, Edwards SM, Brickley MB, Swift RM, Leggio L. Role of the alpha1 blocker doxazosin in alcoholism: a proof-of-concept randomized controlled trial. Addict Biol. 2016 Jul;21(4):904-14. doi: 10.1111/adb.12275. Epub 2015 Jun 2.