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

Phase 1

Completed

Conditions: Alcohol Abstinence

Interventions: Drug: Placebo (for guanfacine)
Drug: Guanfacine XR 3mgs/daily

Registration Number: NCT03137082

Lead Sponsor: Stony Brook University

Brief Summary: 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.

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 32

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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo (for guanfacine)	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)
Guanfacine XR 3mgs/daily	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)

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Mood (Depression)	2 times per week for 12 weeks	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.
Emotion Regulation (Difficulties in Impulse Control)	12-weeks	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.
Emotion Regulation (Limited Access to Emotion Regulation Strategies)	12-weeks	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.
Emotion Regulation (Difficulties With Emotional Awareness)	12-weeks	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.
Emotion Regulation (Non-Acceptance of Emotional Responses)	12-Week	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.
Mood (Anxiety)	2 times per week for 12 weeks	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.
Emotion Regulation (Difficulties With Engaging in Goal Related Behavior)	12-week	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.
Alcohol Craving	12-weeks	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.
Emotion Regulation (Difficulties With Emotional Clarity)	12-weeks	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.
Emotion Regulation (Total Score)	12-weeks	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.