Guanfacine Extended-release for Adolescents With Cannabis Use

Study Overview
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Brief Summary
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A randomized controlled trial to assess the efficacy of extended-release guanfacine to reduce cannabis use frequency in young people with cannabis use disorder following a period of monitored abstinence.

Official Title
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Guanfacine Extended-release Randomised Controlled Trial for Adolescents With Cannabis usE (GRACE)

Conditions
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Cannabis Use Disorder

Intervention / Treatment
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* Drug: Guanfacine Extended Release Oral Tablet
* Behavioral: Residential withdrawal
* Behavioral: Engagement with alcohol and other drug services
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 12-25 years of age (inclusive) at consent; Seeking treatment for cannabis use; DSM-5 Cannabis Use Disorder, mild, moderate or severe; Self-reported cannabis use on average at least 5 days/week during the 28 days prior to screening with a THC positive urine drug screen on the day of screening; and Able to provide informed consent (both adequate IQ and English fluency; <18-year-olds will provide consent themselves in addition to parent/guardian consent). Exclusion Criteria: DSM-5 substance use disorder (moderate or severe) except cannabis or nicotine; Any unstable medical, psychiatric or neurological condition or medical contraindicating study participation; Diagnosis of a psychotic or bipolar illness; Acute suicidality as assessed by clinician; Severe depression (>15 on the Quick Inventory of Depression Symptomatology; QIDS); Prescribed antipsychotics, benzodiazepines or other sedative medications, or other medications for the treatment of ADHD. If prescribed antidepressants, the participant must have been on a stable dose for more than 2 weeks at screening; A history of heart disease or cardiac risk factors (e.g. arrhythmias); Abnormal liver or thyroid function as indicated by clinically-significant findings on blood tests; Pregnancy, breast feeding or, if sexually active and able to become pregnant, no effective contraception. Intention to enter residential rehabilitation after treatment in the YSAS residential withdrawal facility.

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 25 Years

Sexes Eligible for Study
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All

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Guanfacine extended-release<br>Guanfacine extended-release (target dose 4 mg), once daily for approximately 12 weeks plus treatment as usual | Drug: Guanfacine Extended Release Oral Tablet<br>* Target dose 4 mg daily<br>* Other names: Guanfacine XR;Behavioral: Residential withdrawal<br>* 4-14 days in residential withdrawal treatment<br>Behavioral: Engagement with alcohol and other drug services<br>* Ongoing engagement with a youth drug and alcohol service for counselling or other support for the duration of the study<br>|
| Placebo Comparator: Placebo<br>Placebo once daily for approximately 12 weeks plus treatment as usual | Behavioral: Residential withdrawal<br>* 4-14 days in residential withdrawal treatment<br>Behavioral: Engagement with alcohol and other drug services<br>* Ongoing engagement with a youth drug and alcohol service for counselling or other support for the duration of the study<br>Drug: Placebo<br>* Placebo capsule taken daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy - change from baseline in cannabis use frequency following monitored abstinence | Change from baseline in average frequency of cannabis use (days of use/week) in the 4 weeks immediately following discharge from residential withdrawal, assessed weekly using the Timeline Follow-Back. | Baseline and weekly in the 4 week outpatient phase immediately following discharge from residential withdrawal | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in cannabis use frequency following monitored abstinence (categorical) | Change from baseline in average frequency of cannabis use in the 4 weeks immediately following discharge from residential withdrawal, assessed weekly using the Timeline Follow-Back and categorized as follows: heavy use (5-7 days per week), moderate use (3-5 days) or light use (0-1 days) | Baseline and weekly in the 4 weeks immediately following discharge from residential withdrawal | 
| Cannabis exposure | The number of urine toxicology tests that are positive for cannabis exposure | Approximately weekly between Baseline (week 0) and the end of treatment visit (week C7), approximately 12 weeks from baseline | 
| Change from baseline in cannabis use disorder symptoms | Change from baseline in number of cannabis use disorder symptoms endorsed at end of treatment as indexed by the Structured Clinical Interview for DSM-5 (SCID-5) | Baseline and end of Maintenance phase (4 weeks post discharge from residential withdrawal) | 
| Cannabis withdrawal symptoms during residential withdrawal admission | Measured with the Cannabis Withdrawal Scale | Daily during residential treatment for 4 to 14 days | 
| Sleep quality (subjective) during residential withdrawal admission | Measured with the PROMIS Sleep Disturbance Scale | Daily during residential treatment for 4 to 14 days | 
| Cannabis craving during residential withdrawal admission | Measured with the Brief Substance Craving Scale - Cannabis | Daily during residential treatment for 4 to 14 days | 
| Sleep quality (objective) during residential withdrawal admission | Measured with wrist actigraphy | Daily during residential treatment for 4 to 14 days | 
| Food intake during residential withdrawal admission | Measured with a food intake dairy | Daily during residential treatment for 4 to 14 days | 
| Treatment engagement (residential) | Measured as the longest consecutive length of stay in residential withdrawal (4-14 days) | Baseline to end of treatment | 
| Treatment engagement (outpatient) | Measured as the number of outpatient alcohol and other drug counselling sessions completed | Baseline to end of treatment | 
| Change from baseline in daily functioning - social and occupational | Measured with the Social and Occupational Functioning Assessment scale (SOFAS) | Baseline and end of maintenance period assessments (4 weeks post discharge from residential withdrawal) | 
| Change from baseline in daily functioning - multidimensional | Measured with the Multidimensional Adolescent Functioning Scale (MAFS) | Baseline and end of maintenance period assessments (4 weeks post discharge from residential withdrawal) | 
| Change from baseline in daily functioning - social inclusion | Measured with the Filia Social Inclusion Measure - 16 item scale (FSIM-16). | Baseline and end of maintenance period assessments (4 weeks post discharge from residential withdrawal) |