Guanfacine to Improve Substance Use Outcomes in Women

Study Overview
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Brief Summary
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Hypothesis: Guanfacine (GUA) (3mg/day) will reduce drug craving, improve cognitive flexibility and result in associated lower drug use in women with substance use disorder (SUD) in an outpatient clinical setting.

Detailed Description
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This study proposes to extend previous Phase I experimental work to address the following specific aims: (1) assess GUA's target engagement of drug craving and cognitive flexibility in a laboratory challenge session and in a 10-week outpatient clinical study, (2) demonstrate target validation by showing that reduced drug craving and improved cognitive flexibility will predict lower drug use outcomes during the 10-week clinical trial in SUD women, and finally, (3) evaluate data replication and scalability of GUA target effects across two clinical sites (Yale and SUNY-Stony Brook).

Official Title
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The Use of Guanfacine (GUA) (3mg/Day) to Reduce Drug Craving, Improve Cognitive Flexibility and Result in Associated Lower Drug Use in Women With Substance Use Disorder (SUD).

Conditions
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Substance Use Disorders

Intervention / Treatment
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* Drug: Guanfacine
* Other: Behavioral Counseling


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 100 treatment seeking women Ages 18-70 years Body mass index (BMI) of 18-35 Meet current DSM-V criteria for co-occurring SUDs, with primary DSM-V cocaine or primary DSM-V opioid use disorder AND co-occurring cannabis or alcohol or nicotine use disorders; Positive drug urine toxicology screens for primary addictive disorder during a 2-week intake assessment period Good health as verified by screening examination Able to read English and complete study evaluations Able to provide informed written and verbal consent Exclusion Criteria: Meet criteria for physiological dependence on alcohol requiring medical detoxification Regular use of anti-hypertensives, anti-arrythmics, antiretroviral medications, and medications that would interact with Guanfacine and be contraindicated as per study physician; Psychotic or otherwise severely psychiatrically disabled (i.e., suicidal, homicidal, current mania) Significant underlying medical conditions which in the opinion of study physician would preclude patient from fully cooperating or be of potential harm during the course of the study; Specifically hepatic and renal impairment as per liver enzymes at 3X the normal limit, or BUN>50mg or BUN:Cr > 10:1. Hypotensive women with sitting blood pressure below 100/50 mmHG Women who are pregnant, nursing or refuse to use a reliable form of birth control EKG evidence at baseline screening of any clinically significant conduction abnormalities, including a Bazlett's QT c>470 msec for women.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: randomized double blind, placebo controlled
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Study Medication<br>guanfacine 3mg/day (GUA) | Drug: Guanfacine<br>* Guanfacine 3mg/day Versus Placebo<br>* Other names: Tenex,;Other: Behavioral Counseling<br>* placebo<br>* Other names: Manualized Drug Counseling;|
| Placebo Comparator: placebo<br>placebo (PBO) | Drug: Guanfacine<br>* Guanfacine 3mg/day Versus Placebo<br>* Other names: Tenex,;Other: Behavioral Counseling<br>* placebo<br>* Other names: Manualized Drug Counseling;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in drug use with Substance Use Calendar | Days of any drug use during the 10 week period (assessed daily and weekly via self report) | 10 weeks | 
| Change in abstinence days | Substance use calendar self report of daily drug use during 10 week treatment periods | 10 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in average drug craving | Sum of average drug craving measured using Craving Questionnaires for cocaine, opiates, alcohol, nicotine and cannabis. | 10 weeks | 
| Adverse events | Baseline and weekly assessment of SAFTEE questionnaire | 10 weeks |