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Principal Investigator: David Fiellin
Organization: YALE UNIVERSITY
Fiscal Year: 2024
Award: $714,133
Funding agency: National Institute on Alcohol Abuse and Alcoholism
Project Abstract
Alcohol Use Disorder (AUD) is a chronic relapsing illness in which alcohol withdrawal symptoms (AW) are
associated with greater treatment failure risk and higher rates of relapse and alcohol intake. Efficacy of current
approved medications in AUD are modest, and none have been shown to be efficacious in those with AW.
Thus, there is great need to develop and evaluate treatments to address specific prognostic indicators of high
relapse and treatment failure to reduce the associated burden of AUD. Based on this previous clinical
research, we hypothesized that in AUD patients with AW (AUD+AW), PR (16 mg/day) compared to PBO will
significantly improve alcohol use outcomes, craving and also reduce associated anxiety and depression
symptoms and improve physical health (SBP and liver enzymes) functioning and patient-related outcomes
during the course of the trial and with enduring effects during over a 3 month follow up period, thereby
validating AW as a prognostic indicator both of Prazosin efficacy and in AUD treatment outcome. A 12-week
Phase II, single site, randomized clinical trial of Prazosin (PR: 16 mg/day, t.i.d dosing) is proposed in 150
treatment seeking men and women with AUD+ AW (3 or more symptoms) to address the following specific
aims: Aim #1: To evaluate the effects of PR vs PBO on the primary alcohol use outcome of percent of
subjects with no heavy drinking day (PSNHDD) and secondary drinking outcomes of %heavy drinking day
(HDD%), any drinking day (DD%) and average drinks/day (AvgD) in AUD+AW patients. Aim #2: To assess the
effects of PR vs PBO on other secondary stress-related outcomes of alcohol craving, depression and anxiety
symptoms during the trial. Aim #3: To assess enduring short-term treatment effects of PR versus PBO on
primary and other secondary outcomes at 1- and 3- month post-treatment follow-up time points. Exploratory Aim
1: To assess the effects of PR vs PBO treatment during the trial and at follow up on secondary physical health
(SBP/DBP and liver enzymes) and patient-reported functioning outcomes. Exploratory Aim 2: To explore
whether pre-treatment patient characteristics (gender, adversity/trauma history and lifetime PTSD) influence
Prazosin effects on primary and secondary alcohol use and related outcomes. Prazosin is a commonly
prescribed medication that most clinicians feel comfortable using. If successful, findings will provide important
efficacy data on Prazosin’s role in AUD+AW treatment and in related secondary psychological and physical
health outcomes. It will further validate AW at outpatient treatment entry as a prognostic indicator for AUD
treatment and for Prazosin use among AUD+AW subgroup of patients. It will also support development of the
precision medicine goal of providing specific treatment options for AUD patients with AW and stress-related
pathophysiology to improve their AUD treatment outcomes.
Terms: <Accident and Emergency department><Active Follow-up><Address><Adrenal Glands><Adrenals><Adrenergic Antagonists><Adrenergic Blockaders><Adrenergic Blockers><Adrenergic Receptor Antagonists><Adrenergic Receptor Blockaders><Adrenergic-Blocking Agents><Adrenolytic Agents><Adrenolytic Drugs><Adrenolytics><Advertising><After Care><After-Treatment><Aftercare><Alcohol Drinking><Alcohol abuse><Alcohol consumption><Alcohol withdrawal syndrome><Alcoholism><Ambulatory Care><Anti-Adrenergics><Anti-adrenergic Agents><Antiadrenergic Agents><Antiadrenergics><Anxiety><Blood Pressure><Brain><Brain Nervous System><Characteristics><Chronic><Clinical Research><Clinical Study><Consult><Data><Development><Distress><Dose><Double-Blind Method><Double-Blind Study><Double-Blinded><Double-Masked Method><Double-Masked Study><Drug Metabolic Detoxication><Drug Metabolic Detoxification><Drug Prescribing><Drug Prescriptions><Drugs><Dysfunction><Emergency Department><Emergency room><Emotional Depression><Encephalon><Enrollment><Enzyme Gene><Enzymes><EtOH abuse><EtOH drinking><EtOH use><FDA approved><Functional disorder><Furazosin><Gender><Glucuronides><Goals><Health Care Costs><Health Costs><Healthcare Costs><Heavy Drinking><History><Hospitals><Human><Hypothalamic structure><Hypothalamus><Individual><Laboratory Research><Liver><Medical><Medication><Mental Depression><Mental Health><Mental Hygiene><Metabolic Drug Detoxications><Metabolism of Toxic Agents><Modern Man><Neurobiology><Outcome><Outpatient Care><PTSD><Patient Self-Report><Patients><Peripheral><Pharmaceutical Preparations><Phase><Physiopathology><Placebo Control><Placebo Effect><Placebos><Post-Traumatic Neuroses><Post-Traumatic Stress Disorders><Posttraumatic Neuroses><Prazosin><Prevalence><Psychological Health><Public Health><Randomized, Controlled Trials><Recording of previous events><Relapse><Reporting><Research><Risk><Role><Self Assessment><Self-Report><Services><Sham Treatment><Site><Stress><Subgroup><Surgeon><Symptoms><Testing><Time><Titrations><Trauma><Treatment Failure><Treatment outcome><Withdrawal Symptom><Woman><active followup><addiction><addictive disorder><alcohol abuse therapy><alcohol abuse treatment><alcohol co-abuse><alcohol craving><alcohol ingestion><alcohol intake><alcohol problem><alcohol product use><alcohol relapse><alcohol treatment><alcohol use><alcohol use disorder><alcohol withdrawal><alcoholic beverage consumption><alcoholic drink intake><anxiety symptoms><anxious symptom><associated symptom><chronic EtOH drinking><chronic alcohol consumption><chronic alcohol drinking><chronic alcohol ingestion><chronic alcohol use><chronic ethanol consumption><chronic ethanol drinking><chronic ethanol ingestion><co-morbid symptom><co-occuring symptom><comorbid symptom><concurrent symptom><consults><cooccuring symptom><craving><depression><depression symptom><depressive><depressive symptoms><detoxification><developmental><drink heavily><drinking><drug/agent><efficacy testing><enroll><ethanol abuse><ethanol consumption><ethanol craving><ethanol drinking><ethanol ingestion><ethanol intake><ethanol product use><ethanol relapse><ethanol use><ethanol use disorder><ethanol withdrawal><excessive alcohol consumption><excessive alcohol ingestion><excessive alcohol intake><excessive drinking><excessive ethanol ingestion><expectancy effect><expectation effect><extreme drinking><follow up><follow up assessment><follow-up><followed up><followup><followup assessment><functional improvement><hazardous alcohol use><heavy alcohol use><hepatic body system><hepatic organ system><histories><hypothalamic><improve function><improved><improved functional outcomes><medication prescription><men><mood symptom><neurobiological><nocebo><noradrenergic><outpatient treatment><pathophysiology><patient subclass><patient subcluster><patient subgroups><patient subpopulations><patient subsets><patient subtypes><physical conditioning><physical health><placebo controlled><placebo response><post treatment><post-trauma stress disorder><posttrauma stress disorder><precision medicine><precision-based medicine><prescribed medication><problem alcohol use><problem drinking><problematic alcohol consumption><problematic alcohol use><prognostic indicator><randomized control trial><randomized, clinical trials><recruit><relapse risk><response><secondary outcome><sham therapy><social role><stress reduction><suprarenal gland><symptom association><symptom comorbidity><symptom treatment><symptomatic treatment><therapy failure><traumatic neurosis><treat symptom><treatment effect><withdrawal from alcohol>