Guanfacine Extended-release for Adolescents With Cannabis Use (GRACE)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Cannabis Use Disorder
• Intervention / Treatment: Drug: Guanfacine Extended Release Oral Tablet; Behavioral: Residential withdrawal; Behavioral: Engagement with alcohol and other drug services; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Gillinder Bedi, DPsych; Phone Number: +61 3 9966 9100; Email: gill.bedi@orygen.org.au
• Study Contact Backup: Name: Emily A Karanges, PhD; Email: emily.karanges@orygen.org.au

Study Locations

• Australia
  • Victoria
    • Parkville, Victoria, Australia, 3052
      • Recruiting
      • Orygen
      • Contact: Gillinder Bedi, DPsych; Phone Number: +61 3 9966 9100; Email: gill.bedi@orygen.org.au
      • Contact: Holly I Bowman, BPsySc(Hons); Phone Number: +61 3 9966 9100; Email: holly.bowman@orygen.org.au

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. 12-25 years of age (inclusive) at consent;
2. Seeking treatment for cannabis use;
3. DSM-5 Cannabis Use Disorder, mild, moderate or severe;
4. 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
5. 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:

1. DSM-5 substance use disorder (moderate or severe) except cannabis or nicotine;
2. Any unstable medical, psychiatric or neurological condition or medical contraindicating study participation;
3. Diagnosis of a psychotic or bipolar illness;
4. Acute suicidality as assessed by clinician;
5. Severe depression (>15 on the Quick Inventory of Depression Symptomatology; QIDS);
6. 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;
7. A history of heart disease or cardiac risk factors (e.g. arrhythmias);
8. Abnormal liver or thyroid function as indicated by clinically-significant findings on blood tests;
9. Pregnancy, breast feeding or, if sexually active and able to become pregnant, no effective contraception.
10. Intention to enter residential rehabilitation after treatment in the YSAS residential withdrawal facility.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Orygen
• Collaborators: University of Melbourne; Youth Support and Advocacy Service

Study record dates

Study Major Dates

• Study Start (Actual): July 27, 2023
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): June 30, 2026

Study Registration Dates

• First Submitted: June 15, 2023
• First Submitted That Met QC Criteria: July 16, 2023
• First Posted (Actual): July 24, 2023

Study Record Updates

• Last Update Posted (Actual): August 23, 2023
• Last Update Submitted That Met QC Criteria: August 21, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Marijuana Abuse; 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: 22389

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No