Evaluating Tetrahydrocannabinol as an Adjunct to Opioid Agonist Therapy (THC-MMT)

• ClinicalTrials.gov Identifier: NCT05985850
• Recruitment Status: Not yet recruiting
• First Posted: August 14, 2023
• Last Update Posted: November 8, 2023
• Sponsor: BC Centre on Substance Use
• Collaborator: Canadian Institutes of Health Research (CIHR)
• Information provided by (Responsible Party): M. Eugenia Socias, BC Centre on Substance Use

Tracking Information

• First Submitted Date: July 26, 2023
• First Posted Date: August 14, 2023
• Last Update Posted Date: November 8, 2023
• Estimated Study Start Date: January 2024
• Estimated Primary Completion Date: September 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 28, 2023)

• Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] [ Time Frame: 28 weeks ]
  The safety will be evaluated by monitoring and gathering information on physical exam, vital signs, pregnancy testing, adverse events (AE) and serious adverse events (SAE), from the screening visit up to the End of Treatment (EOT)/Early Termination visit. AEs and SAEs will be monitored and recorded throughout the study duration. The proportion of participants who experience AEs or SAEs will be assessed by study arm.
• Risk of Treatment Contamination [ Time Frame: 24 weeks ]
  The proportion of participants using non-study cannabis in the control arm, and proportion of days in Phase 1 where non-study cannabis was used. Self-report of non-study cannabis use will be collected using the Timeline Follow Back (TLFB).
• Participants' adherence to treatment [ Time Frame: 24 weeks ]
  The degree of compliance with the recommended treatment plan, including study drug dosage and administration. This measures how well participants are able to stick to the prescribed treatment regimen and whether or not they are able to complete the full course of treatment. This will be assessed through a self-reported measure, such as study drug diary or treatment logs.
• Acceptability [ Time Frame: 24 weeks ]
  Participant satisfaction with the assigned treatment will be assessed through administration of the Medical Safety Questionnaire (MSQ) every 4 weeks during treatment phase The MSQ is a participant-completed questionnaire that evaluates participant satisfaction with study treatment on a 7-point Likert scale.
• Blinding effectiveness [ Time Frame: 24 weeks ]
  The blinding success questionnaire will be used to evaluate the participants' awareness of their assigned treatment.
• Adequacy of Dose [ Time Frame: 24 weeks ]
  Patient satisfaction with dose level assessed through the adequacy of dose questionnaire and regular consultations

Original Primary Outcome Measures (submitted: August 3, 2023)

• Safety [ Time Frame: 28 weeks ]
  The safety will be evaluated by monitoring and gathering information on physical exam, vital signs, pregnancy testing, adverse events (AE) and serious adverse events (SAE), from the screening visit up to the End of Treatment (EOT)/Early Termination visit. AEs and SAEs will be monitored and recorded throughout the study duration. The proportion of participants who experience AEs or SAEs will be assessed by study arm.
• Risk of Treatment Contamination [ Time Frame: 24 weeks ]
  The proportion of participants using non-study cannabis in the control arm, and proportion of days in Phase 1 where non-study cannabis was used. Self-report of non-study cannabis use will be collected using the Timeline Follow Back (TLFB).
• Participants' adherence to treatment [ Time Frame: 24 weeks ]
  The degree of compliance with the recommended treatment plan, including study drug dosage and administration. This measures how well participants are able to stick to the prescribed treatment regimen and whether or not they are able to complete the full course of treatment. This will be assessed through a self-reported measure, such as study drug diary or treatment logs.
• Acceptability [ Time Frame: 24 weeks ]
  Participant satisfaction with the assigned treatment will be assessed through administration of the Medical Safety Questionnaire (MSQ) every 4 weeks during treatment phase The MSQ is a participant-completed questionnaire that evaluates participant satisfaction with study treatment on a 7-point Likert scale.
• Blinding effectiveness [ Time Frame: 24 weeks ]
  The blinding success questionnaire will be used to evaluate the participants' awareness of their assigned treatment.
• Adequacy of Dose [ Time Frame: 24 weeks ]
  Patient satisfaction with dose level assessed through the adequacy of dose questionnaire and regular consultations

Current Secondary Outcome Measures (submitted: August 3, 2023)

• The number of potential participants referred to the study [ Time Frame: 24 weeks ]
• The screening failure rates [ Time Frame: 24 weeks ]
• The monthly enrolment rates [ Time Frame: 24 weeks ]
• The proportion of eligible participants who are willing to be randomized, willing to initiate the intervention and willing to complete 12-week assessments by study arm [ Time Frame: 24 weeks ]
• The proportion of scheduled study visits completed by study arm [ Time Frame: 24 weeks ]

• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: August 3, 2023)

• Retention in OAT [ Time Frame: 24 weeks ]
  Retention in OAT will be measured by the proportion of participants on OAT at W12 and at W24, defined as having both a) an active OAT prescription at week 12/24, and b) a positive UDT result for the prescribed OAT at week 12/24.
• Illicit opioid use [ Time Frame: 24 weeks ]
  Suppression of illicit opioid use will be measured as the percentage of opioid-free weeks during W1-12, using a combination of Urine Drug Test (UDT) results and self-reported illicit opioid use assessed by the TLFB.
• Pain Intensity [ Time Frame: 24 weeks ]
  The severity of pain will be assessed by the validated scale within the Patient-Reported Outcomes Measurement Information System (PROMIS) 29+2 Profile v2.1 (PROPr): the PROMIS Pain Intensity item.
• Pain Interference [ Time Frame: 24 weeks ]
  The impact of pain on its impact on functioning will be assessed the validated scale within the Patient-Reported Outcomes Measurement Information System (PROMIS) 29+2 Profile v2.1 (PROPr): PROMIS SF v1.0 - Pain Interference 4a scale.
• Anxiety [ Time Frame: 24 weeks ]
  Anxiety symptoms will be assessed by the validated short scale within the PROMIS 29+2 Profile v2.1 (PROPr): the PROMIS SF v1.0 - Anxiety 4a
• Depression [ Time Frame: 24 weeks ]
  Depressive symptoms will be assessed by the validated short scale within the PROMIS 29+2 Profile v2.1 (PROPr): the PROMIS SF v1.0 - Depression 4a.
• Changes in health-related quality of life [ Time Frame: 24 weeks ]
  Changes in health-related quality of life (HRQoL) between screening and the end of treatment will be measured by the PROMIS 29+2 Profile v2.1 (PROPr).
• Changes in substance-use related problems [ Time Frame: 24 weeks ]
  The Addiction Severity Index (ASI) Self-Report form will be used to assess changes in substance-use related problems between Baseline (W0) prior to the start of treatment administration, Treatment Visit at W12 and EOT (W24)/Early Termination.
• Opioid Craving [ Time Frame: 24 weeks ]
  Opioid craving over time will be measured using a 100-mm visual analog scale (VAS), with 11 lines labeled from left to right with the numbers "0" to "10", and word anchors at each end representing the extremes, where "0=no craving" and "100 mm=most intense craving".

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• Brief Title: Evaluating Tetrahydrocannabinol as an Adjunct to Opioid Agonist Therapy
• Official Title: Evaluating Tetrahydrocannabinol as an Adjunct to Opioid Agonist Therapy for Individuals Living With Opioid Use Disorder: A Phase II, Placebo-controlled, Blinded, Pilot Study to Assess Safety and Feasibility (THC-MMT)
• Brief Summary: This pilot study will evaluate the feasibility and safety of using 1:1 tetrahydrocannabinol (THC):Cannabidiol (CBD) cannabis oil as an adjunct therapy to methadone-based Opioid Agonist Therapy (OAT) for individuals with opioid use disorder (OUD) in a community setting.

Detailed Description

This is a single-site, two-phase pilot clinical trial evaluating the safety and feasibility of administering a balanced 1:1 ratio of THC:CBD cannabis oil alongside methadone-based opioid agonist therapy (OAT) in a community setting.

Phase 1 is a 12-week, double-blind, randomized controlled study involving 24 eligible participants with opioid use disorder (OUD) who recently initiated or re-initiated methadone-based OAT. Participants will be randomly assigned to receive either balanced THC:CBD cannabis oil or placebo oil. All participants will receive OUD clinical care, including OAT management, independent of research visits.

After the 12-week blinded treatment period (Phase 1), eligible participants will be invited to Phase 2, a 12-week open-label treatment extension study with all participants receiving balanced THC:CBD cannabis oil. Follow-up research visits will occur every two weeks from the start of open-label treatment.

• Study Type: Interventional
• Study Phase: Phase 2

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Phase 1: 1:1 randomization Phase 2: Open-label

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment

Condition

• Opioid Use Disorder
• Methadone
• Cannabis
• Fentanyl

Intervention

• Drug: Aurora 1:1 Drops (Indica)
  Aurora 1:1 Drops (Indica) is created by extracting cannabinoids and terpenes and the concentrated extract is then diluted in medium-chain triglyceride (MCT) oil for optimal use.
• Drug: Placebo
  Medium-chain triglyceride (MCT) oil with the same appearance, color, and taste as the Aurora 1:1 Drops (Indica).

Study Arms

• Experimental: Aurora 1:1 Drops (Indica)

  Aurora 1:1 Drops (Indica)

  Balanced 1:1 ratio of THC and CBD packaged in a 30 mL bottle:

  THC: 16.8 mg/g (+/- 15%) CBD: 16.8 mg/g (+/- 15%)

  Induction and dosing will be ad libitum and sublingually self-administered. Initial dose will be 5 mg (equivalent to 0.25 mL)/day and participants will be able to titrate in increments of 2.5mg (0.125 mL)/day up to a maximum of 40 mg (2 mL)/day, in consultation with a study physician.

  Intervention: Drug: Aurora 1:1 Drops (Indica)
• Placebo Comparator: Placebo

  Formulated using the same medium chain triglyceride (MCT) oil as Aurora 1:1 Drops (Indica)

  Induction and dosing will be ad libitum and sublingually self-administered. Initial dose will be 5 mg (equivalent to 0.25 mL)/day and participants will be able to titrate in increments of 2.5mg (0.125 mL)/day up to a maximum of 40 mg (2 mL)/day, in consultation with a study physician.

  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Not yet recruiting
• Estimated Enrollment (submitted: August 3, 2023): 24
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: September 2025
• Estimated Primary Completion Date: September 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Individuals of at least 25 years of age or older;
2. Diagnosed with OUD as per DSM-5 criteria;
3. Initiated or re-initiated methadone-based OAT within the past 30 days prior to study entry;
4. Cannabis-use experienced, defined as having used any amount of cannabis in the six months prior to the screening visit;
5. Willing to only use study-provided cannabis as directed by study protocol, including abstention from non-study cannabis and cannabinoids;
6. Agree to keep all study medication stored in a secure location and not to share/distribute study medication to any other individual;

7. If assigned female sex at birth:

   1. Be of non-childbearing potential, defined as (i) postmenopausal (12 months of spontaneous amenorrhea and over 45 years of age); or (ii) documented surgical sterilization (i.e., tubal ligation, hysterectomy, or bilateral oophorectomy); or
   2. If of childbearing potential, be willing to use an acceptable method of contraception throughout the study and have a negative pregnancy test at screening;
8. Ability to understand and comply with study protocol procedures and to provide written informed consent.

Inclusion criteria for Phase 2

In addition to meeting all eligibility criteria outlined in Phase 1, participants will be eligible for Phase 2 provided they meet ALL the following criteria at Week 12:

1. Participants who have not experienced a study medication-related serious adverse event during Phase 1;
2. Participants who have not been lost to follow-up during Phase 1.

Exclusion Criteria:

1. Any disabling, severe, or unstable medical or psychiatric condition that, in the opinion of the study physician, precludes safe participation in the study or the ability to provide fully informed consent, as assessed by medical and psychiatric history, physical examination, vital signs, and/or laboratory tests;
2. Any severe or unstable co-morbid substance use disorder (e.g., delirium tremens, acute alcohol intoxication) that, in the opinion of the study physician, precludes safe participation in the study;
3. Currently pregnant or breastfeeding, or planning to become pregnant;
4. Known or suspected allergy or hypersensitivity to cannabinoids;
5. History of respiratory disease, severe cardiovascular, cerebrovascular, renal or liver disease;
6. Current or historic cannabis use disorder;
7. Taking warfarin, clopidogrel, clobazam, theophylline, clozapine and olanzapine medications as they may interact with cannabinoids in a clinically significant manner if they cannot be switched to a different medication;
8. Any personal or family history (first degree relative) of primary psychotic disorders (i.e., schizophrenia, schizoaffective disorder) as per DSM-5 criteria;
9. Unable to abstain from driving any vehicle or operating machinery for at least 10 hours after taking the study medication. In cases where impairment persists beyond the initial 10-hour period, participants must continue to adhere to these restrictions until the impairment resolves;
10. Actively participating in other interventional clinical trial(s);
11. Incarcerated, pending legal action or other reasons that might prevent completion of the study.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 25 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Josie Kanu, BSc; 6045001102; josie.kanu@bccsu.ubc.ca

• Listed Location Countries: Canada

Administrative Information

• NCT Number: NCT05985850
• Other Study ID Numbers: BCCSU-005
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

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

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: M. Eugenia Socias, BC Centre on Substance Use
• Original Responsible Party: Same as current
• Current Study Sponsor: BC Centre on Substance Use
• Original Study Sponsor: Same as current
• Collaborators: Canadian Institutes of Health Research (CIHR)

Investigators

• Principal Investigator: M Eugenia Socias, MD, MSc.; Assistant Professor, Department of Medicine, University of British Columbia

• PRS Account: BC Centre on Substance Use
• Verification Date: November 2023