A Trial of Guanfacine-er for Cannabis Use Disorder

• ClinicalTrials.gov Identifier: NCT05273567
• Recruitment Status: Recruiting
• First Posted: March 10, 2022
• Last Update Posted: June 8, 2022
• Sponsor: New York State Psychiatric Institute
• Collaborator: National Institute on Drug Abuse (NIDA)
• Information provided by (Responsible Party): Christina Ann Brezing, New York State Psychiatric Institute

Tracking Information

• First Submitted Date: March 1, 2022
• First Posted Date: March 10, 2022
• Last Update Posted Date: June 8, 2022
• Actual Study Start Date: June 1, 2022
• Estimated Primary Completion Date: March 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 1, 2022)

Change in daily cannabis use as measured by ecological momentary assessments (EMA). [ Time Frame: 12 weeks of study ]

Change in number of days of use per week as compared to baseline. Participants will complete ecological momentary assessments (EMA) daily on any internet-accessible device (smart phone, computer, tablet). The daily EMA will assess cannabis use during quartiles of the day. Participants will mark "Yes" if they used cannabis from 12AM-6AM, 6AM-12PM, 12PM-6PM, or 6PM-12AM for each 24 hour period of the study. Primary Outcome will dichotomize each day as a use day (1) or a non using day (0).

• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Trial of Guanfacine-er for Cannabis Use Disorder
• Official Title: A Randomized Controlled Trial of Guanfacine-er for Cannabis Use Disorder
• Brief Summary: The primary purpose of this study is to investigate the effect of guanfacine-ER on reductions in cannabis use and explore its effects on impulsivity and withdrawal through a hybrid in-person and virtual trial of treatment-seeking individuals with Cannabis Use Disorder (CUD), and assessing the feasibility of the virtual components of the study.
• Detailed Description: This will be a 12-week randomized, double-blind, placebo-controlled trial, of guanfacine-ER compared to placebo for CUD. Participants will start on guanfacine-ER 1mg nightly for 1-week (week 1) and slowly increase by 1mg/per week to a max dose of 4mg or maximum dose as tolerated through week 4. Patients will be maintained on the medication through week 11. During week 11, they will begin a taper to discontinuation, decreasing the dose of guanfacine by 1mg every 4 days until stopped during the last week of the study (week 12). The primary purpose of this study is therefore to investigate the effect of guanfacine-ER on reductions in cannabis use and explore its effects on impulsivity and withdrawal through a hybrid in person and virtual trial of treatment-seeking individuals with CUD. In light of COVID-19 viral transmission mitigation policies, we will make use of the technological applications of virtual visits, remote administration of urine drug testing and medication, and ecological momentary assessments (EMA) in conjunction with once monthly in person visits to the clinic during weeks 1, 4, 8, 12.
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Cannabis Use

Intervention

• Drug: guanfacine-ER
  guanfacine-er dispensed daily, starting at 1mg and increasing to 4mg/day or the maximum tolerated dose.
  Other Name: Intuniv-er
• Other: Placebo
  placebo will be dispensed similar to the active arm.

Study Arms

• Experimental: Guanfacine-ER
  Participants will start on guanfacine-ER 1mg nightly for 1-week (week 1) and slowly increase by 1mg/per week to a max dose of 4mg per day or maximum dose as tolerated. Medication taper to discontinuation will begin in week 11 and continue into week 12 until complete by end of study, decreasing the dose by 1mg every 4 days until stopped.
  Intervention: Drug: guanfacine-ER
• Placebo Comparator: Placebo
  Placebo will be taken nightly and titrated and tapered similar to the active arm.
  Intervention: Other: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: March 1, 2022): 90
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: March 2025
• Estimated Primary Completion Date: March 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Meets DSM-V criteria for a current cannabis use disorder
• Seeking treatment for cannabis use disorder with goal to reduce or stop use
• THC-positive drug screen
• Capable of giving informed consent and complying with study procedures
• Access to internet and devices capable of completing study procedures
• capability of receiving mailed packages for study supplies

Exclusion Criteria:

• Lifetime history of DSM-V diagnosis of schizophrenia or schizoaffective disorder
• Current DSM-V criteria for a psychiatric disorder supported by the MINI that in the investigator's judgment is unstable, would be disrupted by the study medication, or is likely to require new pharmacotherapy or psychotherapy during the study period. Individuals who are currently stable on psychotropic medication for at least 2 months may be included if in the investigator's opinion the psychotropic medication is compatible with the study medication (guanfacine-ER). Any medical or psychiatric conditions that in the investigator's judgment would interfere with safe participation in the study will be exclusionary.
• Individuals who meet DSM-V criteria for any moderate to severe substance use disorder other cannabis, caffeine or nicotine use disorders
• Pregnancy, lactation, or failure to use adequate contraceptive method in female patients who are currently engaging in sexual activity that can result in pregnancy
• Legally mandated to participate in a substance use disorder treatment program
• Current or recent history of significant violent or suicidal behavior, risk for suicide or homicide
• Known history of allergy, intolerance, or hypersensitivity to guanfacine
• Bradycardia (< 50 beats/minute), hypotension (sitting or standing BP < 90/50), or symptoms attributable to hypotension (i.e. lightheadedness or dizziness on standing)
• Individuals currently being treated with the antihypertensive medications, including the class of alpha 2 agonists that have a potential drug-interaction with guanfacine based on adrenergic modulation
• Individuals currently taking medications that may interact adversely with guanfacine and deemed not clinically safe by study physician at consent, such as rifampicin, ketoconazole, St. John's Wort, and amitriptyline.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Christina Brezing, MD; 646-774-6132; cb3108@columbia.edu

Contact: Daniel Brooks, LCSW; 9178611270; daniel.brooks@nyspi.columbia.edu

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05273567
• Other Study ID Numbers: 8103; 1K23DA045080-01A1 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Individual participant data that underlie the results published in this report (after de-identification) (text, tables, figures)
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Informed Consent Form (ICF)
• Time Frame: beginning twelve months and ending 5 years after article publication
• Access Criteria: to researcher who provides a methodologically sound proposal to achieve aims in approved proposal

• Current Responsible Party: Christina Ann Brezing, New York State Psychiatric Institute
• Original Responsible Party: Christina Ann Brezing, New York State Psychiatric Institute, Psychiatrist
• Current Study Sponsor: New York State Psychiatric Institute
• Original Study Sponsor: Same as current
• Collaborators: National Institute on Drug Abuse (NIDA)

Investigators

• Principal Investigator: Christina Brezing, MD; NYSPI

• PRS Account: New York State Psychiatric Institute
• Verification Date: June 2022