Clinical trial NCT02164422
Conditions: Alcohol Drinking
Keywords: Alcohol Drinkers Guanfacine
Sponsor: Yale University
Start date: 2014-06-01; Completion date: 2020-03-31
Enrollment: 70 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Evaluating the effect of guanfacine on alcohol consumption. The investigators hypothesize that guanfacine versus placebo will decrease the amount of alcohol consumption (mls consumed) during the 2-hour self-administration period across two laboratory sessions.

Detailed description:

Arms: arm 1: Guanfacine 3mg/day arm 2: Guanfacine 1.5mg/day arm 3: Placebo
Interventions: intervention 1: Guanfacine 3mg/day intervention 2: Guanfacine 1.5mg/day intervention 3: Placebo
Intervention descriptions: intervention 1: 3 mg/day Guanfacine with 3-week lead-in period. Maintained at steady state throughout lab sessions. After lab sessions, given taper supply of medication. Follow up 2 weeks after completion of taper. intervention 2: 1.5 mg/day Guanfacine with 3-week lead-in period. Maintained at steady state throughout lab sessions. After lab sessions, given taper supply of medication. Follow up 2 weeks after completion of taper. intervention 3: None

Protocol documents:
Prot_SAP_000.pdf: 
STUDY PROTOCOL INCLUDING STATISTICAL ANALYSIS PLAN 
OFFICIAL TITLE: Does Guanfacine Attenuate Stress-Induced Drinking? 
BRIEF TITLE: Does Guanfacine Attenuate Stress-Induced Drinking? (Sherry McKee, PhD, PI) 
CLINICALTRIALS.GOV ID: NCT02164422 
PROTOCOL DATE: March 21, 2021 


Identifying effective medications for the treatment of alcohol use disorders remains a high priority as 
problems associated with alcohol use continues to be major public health problem. One promising, yet 
relatively unexplored avenue for medication development for alcohol use are therapeutics that target 
stress-reactivity. Several lines of evidence suggest that stress is a primary mediator of alcohol use and 
relapse. Preclinical research demonstrates that noradrenergic pathways are involved in stress-induced 
consumption and reinstatement to alcohol, as well as alcohol-related reinforcement and withdrawal, 
and that their manipulation may be of potential therapeutic benefit for alcohol use.  
Guanfacine is an alpha2a adrenergic receptor agonist known to attenuate stress-induced reinstatement 
to alcohol and other drugs of abuse in preclinical studies. Guanfacine rescues the prefrontal cortex from 
detrimental effects of stress and improves working memory, attention, and behavioral control. In a 
study evaluating 3mg/day guanfacine for smoking cessation, we demonstrated that guanfacine was well 
tolerated, attenuated the effects of stress on smoking, reduced smoking-related reinforcement, 
improved cognition, and significantly reduced smoking during a brief treatment phase.  
 
STUDY OBJECTIVE 
To conduct a Phase II human laboratory study evaluating the effect of guanfacine on alcohol 
consumption. Using a double-blind, placebo-controlled, dose-ranging parallel group design, we 
randomized non-treatment seeking adults with alcohol use disorders (DSM-IV dependence or abuse) to 
guanfacine (3mg/day, 1.5mg/day, or placebo) to evaluate whether guanfacine reduces alcohol self-
administered in the laboratory. Following titration to steady state medication levels over a 3-week 
period, each subject will complete two laboratory sessions to evaluate drinking during a 2-hour alcohol 
self-administration paradigm. 
 
STUDY DESIGN AND METHODS 
This study was a double-blind, placebo controlled, parallel-group design, to compare immediate release 
guanfacine (1.5, 3.0mg/day) to placebo (0mg/day) in adults meeting criteria for DSM-IV alcohol use 
disorders. This study consisted of an intake session, a physical exam, and two laboratory sessions 
following titration to steady state levels. Ad-lib alcohol consumption was assessed during the 2-hour 
session. Doses designed to raise alcohol to 0.12 g/dL were provided. Following the medication taper, 
subjects were assessed for an additional two weeks. Primary outcome measures include mls consumed 
during the self-administration sessions, and secondarily, the frequency and severity of adverse events 
during the titration period. 
 
ELIGIBILTY 
Minimum Age: 21 Years   
Maximum Age: 65 Years   
Sex: 
All   
Gender Based:   


Accepts Healthy Volunteers: 
Yes   
Criteria: 
Inclusion Criteria: 
Age 21-65 
Able to read and write English 
Meets Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria for current (past 6 
months) alcohol abuse or alcohol dependence 
Exclusion Criteria: 
Participants with any significant current medical conditions, seizures, delirium or hallucinations, or other 
unstable medical conditions including HIV 
Current DSM-IV abuse or dependence on substances, other than alcohol abuse, alcohol dependence, or 
nicotine dependence 
Women who are pregnant or nursing 
Suicidal, homicidal or evidence of current (past 6-month) mental illness 
Meet DSM-IV criteria for current (past-6 month) attention deficit hyperactivity disorder (ADHD) 
Specific exclusions for administration of guanfacine not already specified include: EKG evidence at 
baseline screening of any clinically significant conduction abnormalities or arrhythmias; known 
intolerance for guanfacine or any alpha blocker; history of fainting, syncopal attacks, heart failure or 
myocardial infarction, or impaired liver as indicated by aspartate aminotransferase (AST), alanine 
aminotransferase (ALT) > 3x normal or renal function (estimated creatinine clearance <60 cc/min); 
treatment with any antihypertensive drug or any alpha-adrenergic blocker; use of any central nervous 
system (CNS) depressant (e.g., phenothiazines, barbiturates, benzodiazepines) 
Subjects likely to exhibit clinically significant alcohol withdrawal during the study. 
Individuals who are seeking treatment for drinking 
 
STATISTICIAL CONSIDERATIONS 
PRIMARY HYPOTHESIS: During the laboratory component, 3mg/day guanfacine and 1.5mg/day 
guanfacine vs placebo will reduce alcohol consumption. Linear mixed models with medication condition, 
lab session, and time were used to evaluate mls consumed.