Guanfacine to Improve Substance Use Outcomes in Women

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).

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.

Study Overview

• Status: Completed
• Conditions: Substance Use Disorders
• Intervention / Treatment: Drug: Guanfacine; Other: Behavioral Counseling

Detailed Description

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).

• Study Type: Interventional
• Enrollment (Actual): 74
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Rachel Hart; Phone Number: 203-737-5689; Email: rachel.hart@yale.edu

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06519
      • The Yale Stress Center: Yale University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Study Medication; guanfacine 3mg/day (GUA)	Drug: Guanfacine; Guanfacine 3mg/day Versus Placebo; Other Names: Tenex,; Other: Behavioral Counseling; placebo; Other Names: Manualized Drug Counseling
Placebo Comparator: placebo; placebo (PBO)	Drug: Guanfacine; Guanfacine 3mg/day Versus Placebo; Other Names: Tenex,; Other: Behavioral Counseling; placebo; Other Names: Manualized Drug Counseling

What is the study measuring?

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). Data presented here is the average between week 10 and week 1.	10 weeks
Change in Abstinence Days	Substance use calendar self report of daily drug use during 10 week treatment periods. Data presented here is the average between week 10 and week 1.	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.The possible range for the average craving measure is 0 - 100. A higher score on the measure = greater avg drug craving.	10 weeks
Number of Participants With Treatment Emergent Adverse Event	The Systematic Assessment of Treatment Emergent Events (SAFTEE) Questionnaire will be used to assess adverse events weekly during the trial. Data presented here is the number of participants that had any adverse events while on study.	10 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Stress Scores	Repeated assessment of 14-item Perceived Stress Scale (score range: 0-53, higher scores are worse) assessed weekly. Scores are the average change between week 10 and week 1.	10 weeks
Change in Anxiety Levels	Repeated assessment of 14-item Hamilton Anxiety Scale (score range: 0-56, higher score is worse outcome) assessed weekly over 10 weeks. Scores are the average change between week 10 and week 1.	10 weeks
Change in Depression Levels	Repeated assessment of 17-item Hamilton Depression Scale (score range: 0-53, higher score is worse outcome) assessed weekly over 10 weeks. Scores are the average change between week 10 and week 1.	10 weeks

Collaborators and Investigators

• Sponsor: Yale University
• Collaborators: National Institute on Drug Abuse (NIDA)
• Investigators: Principal Investigator: Rajita Sinha, PhD, Yale University

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2019
• Primary Completion (Actual): November 30, 2022
• Study Completion (Actual): November 30, 2022

Study Registration Dates

• First Submitted: March 29, 2019
• First Submitted That Met QC Criteria: June 6, 2019
• First Posted (Actual): June 10, 2019

Study Record Updates

• Last Update Posted (Actual): March 20, 2024
• Last Update Submitted That Met QC Criteria: March 18, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; 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: 2000023100; 1R01DA047094-01A1 (U.S. NIH Grant/Contract)

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.: Yes