Substance Use Disorders
Conditions
Brief summary
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
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).
Interventions
DRUGGuanfacine
Guanfacine 3mg/day Versus Placebo
placebo
Sponsors
National Institute on Drug Abuse (NIDA)
Yale University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
double blind
Intervention model description
randomized double blind, placebo controlled
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 70 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Drug Use With Substance Use Calendar | 10 weeks | 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. |
| Change in Abstinence Days | 10 weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment Emergent Adverse Event | 10 weeks | 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. |
| Change in Average Drug Craving | 10 weeks | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change in Stress Scores | 10 weeks | 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. |
| Change in Anxiety Levels | 10 weeks | 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. |
| Change in Depression Levels | 10 weeks | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Study Medication guanfacine 3mg/day (GUA)
Guanfacine: Guanfacine 3mg/day Versus Placebo
Behavioral Counseling: placebo | 36 |
| Placebo placebo (PBO)
Guanfacine: Guanfacine 3mg/day Versus Placebo
Behavioral Counseling: placebo | 34 |
| Total | 70 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Dropped out before treatment | 2 | 2 |
| Overall Study | Lost to Follow-up | 11 | 13 |
Baseline characteristics
| Characteristic | Total | Placebo | Study Medication |
|---|---|---|---|
| Addiction Severity Index Score (ASI) | 6.5 score on a scale STANDARD_DEVIATION 2.3 | 6.4 score on a scale STANDARD_DEVIATION 2.5 | 6.6 score on a scale STANDARD_DEVIATION 2.5 |
| Age, Continuous | 40 years STANDARD_DEVIATION 12.5 | 40.1 years STANDARD_DEVIATION 12.5 | 39.5 years STANDARD_DEVIATION 12.5 |
| Education | 13.3 years STANDARD_DEVIATION 2.1 | 13.2 years STANDARD_DEVIATION 2 | 13.4 years STANDARD_DEVIATION 2.1 |
| Married/Cohabitating | 12 Participants | 6 Participants | 6 Participants |
| Mean days alcohol use in the past 30 days | 14.4 days STANDARD_DEVIATION 9.5 | 13.8 days STANDARD_DEVIATION 8.9 | 15 days STANDARD_DEVIATION 10.1 |
| Mean days cannabis use in the past 30 days | 19.8 days STANDARD_DEVIATION 11.8 | 20 days STANDARD_DEVIATION 12.7 | 19.7 days STANDARD_DEVIATION 11.3 |
| Mean days cocaine use in the past 30 days | 12.7 days STANDARD_DEVIATION 10.6 | 11.0 days STANDARD_DEVIATION 8.7 | 14 days STANDARD_DEVIATION 12.1 |
| Mean days opioid use in the past 30 days | 16.4 days STANDARD_DEVIATION 12.6 | 20.6 days STANDARD_DEVIATION 11.5 | 12.1 days STANDARD_DEVIATION 12.7 |
| Mean days tobacco use in the past 30 days | 28.7 days STANDARD_DEVIATION 5.3 | 29.2 days STANDARD_DEVIATION 4.5 | 28.1 days STANDARD_DEVIATION 6 |
| Number of participants that used alcohol in the past 30 days | 61 Participants | 30 Participants | 31 Participants |
| Number of participants that used cannabis in the past 30 days | 51 Participants | 24 Participants | 27 Participants |
| Number of participants that used cocaine in the past 30 days | 52 Participants | 26 Participants | 26 Participants |
| Number of participants that used opioids in the past 30 days | 48 Participants | 23 Participants | 25 Participants |
| Number of participants that used tobacco in the past 30 days | 61 Participants | 31 Participants | 30 Participants |
| Race/Ethnicity, Customized Black | 19 Participants | 9 Participants | 10 Participants |
| Race/Ethnicity, Customized Caucasian | 43 Participants | 23 Participants | 20 Participants |
| Race/Ethnicity, Customized Hispanic | 10 Participants | 3 Participants | 7 Participants |
| Race/Ethnicity, Customized Other | 8 Participants | 2 Participants | 6 Participants |
| Region of Enrollment United States | 70 participants | 34 participants | 36 participants |
| Sex: Female, Male Female | 70 Participants | 34 Participants | 36 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 38 | 0 / 36 |
| other Total, other adverse events | 19 / 36 | 11 / 34 |
| serious Total, serious adverse events | 2 / 36 | 4 / 34 |
Outcome results
Primary
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.
Time frame: 10 weeks
Population: Participants who were randomized and received treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Study Medication | Change in Abstinence Days | 0.28 days | Standard Deviation 0.25 |
| Placebo | Change in Abstinence Days | -0.12 days | Standard Deviation 0.24 |
p-value: <0.001Fisher Exact
Primary
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.
Time frame: 10 weeks
Population: Participants who were randomized and received treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Study Medication | Change in Drug Use With Substance Use Calendar | -6.35 days | Standard Deviation 1 |
| Placebo | Change in Drug Use With Substance Use Calendar | -5.61 days | Standard Deviation 0.96 |
p-value: 0.08Fisher Exact
Secondary
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.
Time frame: 10 weeks
Population: Participants who were randomized and received treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Study Medication | Change in Average Drug Craving | -14.6 score on a scale | Standard Deviation 4.4 |
| Placebo | Change in Average Drug Craving | -21.9 score on a scale | Standard Deviation 5.9 |
p-value: 0.703Fisher Exact
Secondary
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.
Time frame: 10 weeks
Population: Participants who were randomized and received treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Study Medication | Number of Participants With Treatment Emergent Adverse Event | 21 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Event | 15 Participants |
Other Pre-specified
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.
Time frame: 10 weeks
Population: Participants who were randomized and received treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Study Medication | Change in Anxiety Levels | -1.9 score on a scale | Standard Deviation 2.2 |
| Placebo | Change in Anxiety Levels | -0.8 score on a scale | Standard Deviation 1.3 |
p-value: 0.647Fisher Exact
Other Pre-specified
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.
Time frame: 10 weeks
Population: Participants who were randomized and received treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Study Medication | Change in Depression Levels | 0.5 score on a scale | Standard Deviation 2.3 |
| Placebo | Change in Depression Levels | 0.6 score on a scale | Standard Deviation 1.4 |
p-value: 0.887Fisher Exact
Other Pre-specified
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.
Time frame: 10 weeks
Population: Participants who were randomized and received treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Study Medication | Change in Stress Scores | -2.8 score on a scale | Standard Deviation 2.9 |
| Placebo | Change in Stress Scores | 7.8 score on a scale | Standard Deviation 2.8 |
p-value: 0.002Fisher Exact