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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Alcohol Abstinence

Intervention / Treatment
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* Drug: Guanfacine XR 3mgs/daily
* Drug: Placebo (for guanfacine)


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Guanfacine XR 3mgs/daily<br>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<br>* Guanfacine 3mg tablet<br>* Other names: Intuniv;|
| Placebo Comparator: Placebo (for guanfacine)<br>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)<br>* Sugar pill manufactured to mimic guanfacine tablets<br>* Other names: Sugar pill;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Alcohol Consumption | Ethyl glucuronide (Etg) urine toxicology screens will be collected two times per week, to assess drinking status | 10 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Attrition rate (%) | The percentage number of participants dropping out of the study will be calculated for both the experimental and control group | 10 weeks | 
| Alcohol Craving | The Alcohol Urges Questionnaire (AUQ) will be administered 2 times per week to assess changes in craving. The scale comprises 8 craving-related statements ranging from 1(Strongly Disagree) to 7(Strongly Agree), yielding a total ranging from 7 to 56. The higher the score, the higher the reported craving. | 10 weeks | 
| Mood | The Profile of Mood States (POMS) will be administered 2 times per week to assess changes in mood. The scale comprises 72 adjectives that describe different feelings, and participants are required to rate the extent to which they are experiencing each feeling at the moment, from 0= not at all; 1= a little; 2= moderately; 3= quite a bit; 4= extremely. Subscales include: Tension; Depression; Anxiety; Fatigue; Confusion; Vigor | 10 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Stress, Alcohol Use Disorder, Guanfacine, Craving, Gender, Relapse