Clinical trial NCT03137082: Guanfacine to Reduce Relapse Risk in Women With Alcohol Use Disorder (AUD)
Official title: Guanfacine to Reduce Relapse Risk in Women With Alcohol Use Disorder (AUD)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Alcohol Abstinence
Keywords: Alcohol Use Disorder
Guanfacine
Stress
Craving
Gender
Relapse
Lead sponsor: Stony Brook University
Sponsor class: OTHER
First posted: 2017-05-02
Enrollment: 32
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Days Abstinent
timeFrame: 12 weeks
measure: Percentage of Heavy Drinking Days
timeFrame: 12 weeks
measure: Alcohol Consumption (Percentage of Negative Urines)
timeFrame: 12 weeks
Secondary outcomes:
measure: Mood (Anxiety)
timeFrame: 2 times per week for 12 weeks
measure: Mood (Depression)
timeFrame: 2 times per week for 12 weeks
measure: Alcohol Craving
timeFrame: 12-weeks
measure: Emotion Regulation (Difficulties in Impulse Control)
timeFrame: 12-weeks
measure: Emotion Regulation (Difficulties With Engaging in Goal Related Behavior)
timeFrame: 12-week
measure: Emotion Regulation (Difficulties With Emotional Clarity)
timeFrame: 12-weeks
measure: Emotion Regulation (Limited Access to Emotion Regulation Strategies)
timeFrame: 12-weeks
measure: Emotion Regulation (Difficulties With Emotional Awareness)
timeFrame: 12-weeks
measure: Emotion Regulation (Non-Acceptance of Emotional Responses)
timeFrame: 12-Week
measure: Emotion Regulation (Total Score)
timeFrame: 12-weeks
Other outcomes:
Locations:
city: Stony Brook
country: United States
facility: The Health Sciences Center
state: New York
Study officials:
affiliation: Stony Brook University
name: Helen C Fox, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.