Guanfacine to Reduce Relapse Risk in Women With Alcohol Use Disorder (AUD)

Guanfacine may preferentially reduce craving and improve cognitive control in women with Alcohol Use Disorder (AUD), compared to men. As these behaviors are related to relapse, the objectives of this study are to conduct a 10-week out-patient clinical trial to examine the effects of Guanfacine Extended Release (XR; 3mgs) versus placebo on drinking measures in women with AUD.

Study Overview

• Status: Completed
• Conditions: Alcohol Abstinence
• Intervention / Treatment: Drug: Guanfacine XR 3mgs/daily; Drug: Placebo (for guanfacine)

Detailed Description

Gender-specific variation in sympathetic sensitivity (Fox et al., 2014; Fox and Sinha, 2009; Cahill, 2003; Heinsbroek et al., 1991) may mean that guanfacine is particularly efficacious in attenuating drinking in women, rather than men with Alcohol Use Disorder (AUD). Thus, the investigators propose a double blind, placebo-controlled, 10-week randomized clinical trial to examine the effects of Guanfacine XR (3mgs/daily) versus placebo in 60 women with AUD. This will include twice weekly appointments comprising medical management and contingency management protocols, collection of urine, breathalyzer screens, and vitals. Measures of craving and mood will also be assessed. Parallel laboratory challenge studies will also be conducted both on admission to out-patient treatment and again following 4 weeks of treatment, in order to better elucidate the potentially therapeutic mechanisms of guanfacine. Participants will be exposed to a personal stress versus relaxing imagery condition, 1 condition per day, in a randomized order. Craving, anxiety, mood, cognitive control, heart rate and blood pressure (HRBP), and biological stress system markers will be assessed at baseline, following imagery and at various recovery timepoints.

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • Stony Brook, New York, United States, 11794
      • The Health Sciences Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Must meet Diagnostic and Statistical Manual of Mental Disorders-V (DSM- V) criteria for moderate to severe Alcohol Use Disorder (AUD),
• Must produce positive urine toxicology screens on admission to study
• Must demonstrate good health as verified by screening examination
• Must be able to read English and complete study evaluations
• Must be able to provide informed written and verbal consent

Exclusion Criteria:

• Meeting current use disorder for any other psychoactive substance, excluding nicotine.
• Having any other current Axis I psychiatric disorders or medical conditions requiring treatment or medication
• EKG evidence at baseline screening of any clinically significant conduction abnormalities including a Bazlett's QTc (corrected QT interval) of >470 msec.
• Must not be on monophasic contraceptives, nursing or pregnant.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Guanfacine XR 3mgs/daily; Guanfacine XR tablet by mouth every 24 hours for 12 weeks; 21 day titration: 1 mg/d (day 1-7); 2mgs/d (day 7-21); Full dose: 3mgs/d (day 21- day 70); 2 week taper: 2mgs/d (day 71-77); 1mg/d (day 77-83)	Drug: Guanfacine XR 3mgs/daily; Guanfacine 3mg tablet; Other Names: Intuniv
Placebo Comparator: Placebo (for guanfacine); Guanfacine XR tablet by mouth every 24 hours for 12 weeks; 21 day titration: 1 mg/d (day 1-7); 2mgs/d (day 7-21); Full dose: 3mgs/d (day 21- day 70); 2 week taper: 2mgs/d (day 71-77); 1mg/d (day 77-83)	Drug: Placebo (for guanfacine); Sugar pill manufactured to mimic guanfacine tablets; Other Names: Sugar pill

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Days Abstinent	Percentage of days abstinent across the 12-week trial was calculated using the Timeline follow Back.	12 weeks
Percentage of Heavy Drinking Days	Percentage of heavy drinking days across the 12-week trial was calculated using the Timeline follow Back.	12 weeks
Alcohol Consumption (Percentage of Negative Urines)	Urine screening will be conducted twice per week across the trial.	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mood (Anxiety)	The Anxiety subscale of the Profile of Mood States (POMS) was administered to assess anxiety. The subscale comprises 9 adjectives that describe anxiety-related feelings, and participants are required to rate the extent to which they are experiencing each feeling at that moment, from 0= not at all; 1= a little; 2= moderately; 3= quite a bit; 4= extremely. Possible scores range from 0 to 36, with higher scores representing higher levels of anxiety. Anxiety ratings were collected two times per week across twelve weeks (24 time-points). Each time-point represented change from baseline anxiety. The calculation here represents mean change from baseline values across the 12 weeks, where minus scores represent lower mean anxiety compared with baseline.	2 times per week for 12 weeks
Mood (Depression)	The Depression subscale of the Profile of Mood States (POMS) was administered to assess depression. The subscale comprises 15 adjectives that describe depression-related feelings, and participants are required to rate the extent to which they are experiencing each feeling at that moment, from 0= not at all; 1= a little; 2= moderately; 3= quite a bit; 4= extremely. Possible scores range from 0 to 60, with higher scores representing higher levels of depression. Depression ratings were collected two times per week across twelve weeks (24 time-points). Each time-point represented change from baseline depression. The calculation here represents mean change from baseline values across the 12 weeks, where minus scores represent lower mean depression compared with baseline.	2 times per week for 12 weeks
Alcohol Craving	The desire for using alcohol was assessed using a 10-point visual analog scale (VAS) in which 1 = 'not at all' and 10 = 'extremely high'. Alcohol craving ratings were collected two times per week across twelve weeks (24 time-points). Each time-point represented change from baseline alcohol craving. The calculation here represents mean change from baseline values across the 12 weeks, where minus scores represent lower mean alcohol craving compared with baseline.	12-weeks
Emotion Regulation (Difficulties in Impulse Control)	We used the Impulse Control Difficulties subscale (IMPULSE) of the Difficulties in Emotion Regulation Scale (DERS) to assess changes in impulse control across the trial. The DERS was administered two times per week, and the IMPULSE subscale comprised 6 items with a potential score range of 6 to 30 with higher scores representing greater difficulties in impulse control. Each time-point represents change from baseline impulse control difficulties. The calculation here represents mean change from baseline values across the 12 weeks, where minus values represent less difficulties in impulse control compared with baseline.	12-weeks
Emotion Regulation (Difficulties With Engaging in Goal Related Behavior)	We used the Difficulties in Engaging in Goal-Directed Behavior (GOALS) subscale of the Difficulties in Emotion Regulation Scale (DERS) to assess changes in goal-directed behavior across the trial. The DERS was administered two times per week (24 time-points) and the GOALS subscale comprised 5 items with a potential score range of 5 to 25 with higher scores representing greater difficulties in engaging in goal-directed behavior. Each time-point represented change from baseline GOALS. The calculation here represents mean change from baseline values across the 12 weeks, where minus values represent less difficulties in engaging in goal-directed behavior compared with baseline.	12-week
Emotion Regulation (Difficulties With Emotional Clarity)	We used the Lack of Emotional Clarity subscale (CLARITY) of the Difficulties in Emotion Regulation Scale (DERS) to assess changes in emotional clarity across the trial. The DERS was administered two times per week, and the CLARITY subscale comprised 5 items with a potential score range of 5 to 25 with higher scores representing greater difficulties in emotional clarity. Each time-point represents change from baseline difficulties in emotional clarity. The calculation here represents mean change from baseline values across the 12 weeks, where minus values represent less difficulties in emotional clarity compared with baseline.	12-weeks
Emotion Regulation (Limited Access to Emotion Regulation Strategies)	We used the Limited Access to Emotion Regulation Strategies subscale (STRATEGIES) of the Difficulties in Emotion Regulation Scale (DERS) to assess changes in ability to access emotion regulation strategies across the trial. The DERS was administered two times per week, and the STRATEGIES subscale comprised 8 items with a potential score range of 8 to 40 with higher scores representing greater difficulties in accessing emotion regulation strategies. Each time-point represents change from baseline STRATEGIES. The calculation here represents mean change from baseline values across the 12 weeks, where minus values represent less difficulties in accessing emotion regulation strategies compared with baseline.	12-weeks
Emotion Regulation (Difficulties With Emotional Awareness)	We used the Lack of Emotional Awareness subscale (AWARENESS) of the Difficulties in Emotion Regulation Scale (DERS) to assess changes in emotional awareness across the trial. The DERS was administered two times per week, and the AWARENESS subscale comprised of 6 items with a potential score range of 6 to 30 with higher scores representing greater a greater lack of emotional awareness. Each time-point represents change from baseline emotional awareness. The calculation here represents mean change from baseline values across the 12 weeks, where minus values represent less difficulties in emotional awareness compared with baseline.	12-weeks
Emotion Regulation (Non-Acceptance of Emotional Responses)	We used the Non-Acceptance of Emotional Responses subscale (NON-ACCEPTANCE) of the Difficulties in Emotion Regulation Scale (DERS) to assess changes in non-acceptance of emotional responses across the trial. The DERS was administered two times per week, and the NON-ACCEPTANCE subscale comprised 6 items with a potential score range of 6 to 30 with higher scores representing greater difficulties in acceptance of emotional response. Each time-point represents change from baseline NON-ACCEPTANCE. The calculation here represents mean change from baseline values across the 12 weeks, where minus values represent less difficulties regarding non-acceptance of emotional responses compared with baseline.	12-Week
Emotion Regulation (Total Score)	We used the Total score of the Difficulties in Emotion Regulation Scale (DERS) to assess changes in overall emotion regulation across the trial. The DERS was administered two times per week, and comprised 41 items with a potential score range of 41 to 164 with higher scores representing greater difficulties in emotion regulation. Each time-point represents change from baseline emotion regulation difficulties. The calculation here represents mean change from baseline values across the 12 weeks, where minus values represent less difficulties regarding emotion regulation compared with baseline.	12-weeks

Collaborators and Investigators

• Sponsor: Stony Brook University
• Investigators: Principal Investigator: Helen C Fox, PhD, Stony Brook University

Publications and helpful links

General Publications

• Fox HC, Morgan PT, Sinha R. Sex differences in guanfacine effects on drug craving and stress arousal in cocaine-dependent individuals. Neuropsychopharmacology. 2014 May;39(6):1527-37. doi: 10.1038/npp.2014.1. Epub 2014 Jan 7.
• Fox HC, Sinha R. Sex differences in drug-related stress-system changes: implications for treatment in substance-abusing women. Harv Rev Psychiatry. 2009;17(2):103-19. doi: 10.1080/10673220902899680.
• Heinsbroek RP, van Haaren F, Feenstra MG, Boon P, van de Poll NE. Controllable and uncontrollable footshock and monoaminergic activity in the frontal cortex of male and female rats. Brain Res. 1991 Jun 14;551(1-2):247-55. doi: 10.1016/0006-8993(91)90939-s.
• Cahill L. Sex-related influences on the neurobiology of emotionally influenced memory. Ann N Y Acad Sci. 2003 Apr;985:163-73. doi: 10.1111/j.1749-6632.2003.tb07080.x.

Study record dates

Study Major Dates

• Study Start (Actual): July 12, 2017
• Primary Completion (Actual): March 31, 2021
• Study Completion (Actual): March 31, 2021

Study Registration Dates

• First Submitted: April 24, 2017
• First Submitted That Met QC Criteria: April 27, 2017
• First Posted (Actual): May 2, 2017

Study Record Updates

• Last Update Posted (Actual): June 5, 2024
• Last Update Submitted That Met QC Criteria: May 7, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Stress; Craving; Alcohol Use Disorder; Relapse; Guanfacine; Gender
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Pathologic Processes; Drinking Behavior; Alcohol-Related Disorders; Substance-Related Disorders; Disease Attributes; Alcohol Drinking; Alcoholism; Recurrence; Alcohol Abstinence; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Guanfacine
• Other Study ID Numbers: R21AA024880 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No