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Opioid-Sparing Effect of Oral Cannabinoids

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ClinicalTrials.gov Identifier: NCT05351905
Recruitment Status : Recruiting
First Posted : April 28, 2022
Last Update Posted : November 29, 2022
Sponsor:
Information provided by (Responsible Party):
Jo Carroll, University Health Network, Toronto

Brief Summary:
The investigators are conducting a pilot (i.e. a small study) in order to find out the effectiveness and safety of medical cannabis in the management of chronic pain. At the end of this 3 month study, investigators will gather information on how easy it is for patients to enroll and complete the entire study. The results of this pilot study will then be used to determine if the weaning protocol is useful and help the study team design a larger randomized controlled trial.

Condition or disease Intervention/treatment Phase
Chronic Pain Opioid Use Cannabis Drug: CBD oil ( MPL-001) Drug: CDB+THC oil (MPL-005) Drug: Placebo oil Not Applicable

Detailed Description:

Chronic pain is defined as pain lasting longer than three months, affects ~20% of Canadian adults. In addition to having a significant negative impact at the individual patient level (i.e., decreased quality of life and functioning), chronic pain is also a main cause of disability and health care use. Opioids are frequently prescribed to manage chronic pain despite limited data on their long term usefulness and has become one of the major contributors to the current opioid crisis in Canada. Chronic pain can potentially be treated with medical cannabis as an adjunct or alternative to opioids due to their similar behavioral, anatomical and biochemical mechanisms. Cannabinoids also potentially prevent the development of tolerance to opioids when co-administered.

Cannabinoids have demonstrated opioid-sparing effects in pre-clinical and clinical studies however further research is needed to identify the optimal make-up, ratio, and dosage of cannabinoids to minimize harms and maximize benefits. Furthermore, studies conducted to date have methodological problems such as short follow-up windows (hours or days) that limit conclusions. The investigators therefore propose a randomized, placebo-controlled trial of oral cannabinoids [CBD (cannabidiol) alone or in combination with THC (delta-9-tetrahydrocannabinol)] for decreasing opioid use and pain management in chronic pain. However, there are a number of feasibility issues that should be addressed prior to launching a full-scale trial in this area. Some issues have been identified in the literature (e.g., success of blinding) while others are related to the changing socio-medico-legal landscape surrounding cannabis use in Canada.

The purpose of this pilot study is to test the study plan, patient recruitment and compliance with the study procedures. The results may be used as a guide for larger studies, and help us determine the use of medical cannabis in reducing or replacing prescription opioids in the treatment of chronic pain.

This study will aim to recruit 51 patients from the Toronto General Hospital Transitional Pain Service.

Study Procedure: After obtaining the Informed consent, patients will be randomized into one of the three study groups. Patients will either receive CBD oil, CBD+THC oil or placebo orally for 12 weeks. Starting dose will be 1 ml per day. The dose of study drug will be adjusted based on patients' reported efficacy and adverse effects. After starting the study drug, patients will have scheduled clinic visits at 4, 8, and 12 weeks plus a follow up calls or virtual clinic visit(OTN) at 2 and 6 weeks. At every study visit, patients will be asked to complete the questionnaires that will assess their pain level and how it affects their quality of life, opioid use, and side effects if they are experiencing. The investigators will also collect information on: demographic and baseline characteristics (e.g., sex, age, height, weight, and body mass index) and medical history (including prior and concomitant medications) via patient interview or from inspection of medical records. Additionally, symptoms of depression and anxiety will be measured with the validated screening tools at baseline and 12 weeks post-treatment.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 51 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Participants will be randomized to receive either a placebo, CBD oil (medical cannabis) or CBD+THC oil (medical cannabis) in a 1:1:1 ratio.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: The patients, study staff, care providers, adjudicators, data analysts and investigators will be blinded to the active ingredient(s) in the study medication and group allocation. Blinding of all research team members who interact with the patient will avoid biases in communications with, or treatment of, participants based on group allocation. Blinding of research participants will avoid any bias in reporting (e.g., of pain ratings, side effects) and actions/behaviours during the study (e.g., opioid medication dose adjustments) based on group allocation and/or expectations.
Primary Purpose: Treatment
Official Title: A Single-centre, Pilot, Randomized Controlled Trial of Oral Cannabinoids for Decreasing Opioid Use and Pain Management in Patients With Chronic Pain
Actual Study Start Date : November 22, 2022
Estimated Primary Completion Date : May 2023
Estimated Study Completion Date : December 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Chronic Pain

Arm Intervention/treatment
Experimental: CBD oil
Participants will receive CBD (cannabidiol) oil for a total duration of 12 weeks.
Drug: CBD oil ( MPL-001)
MPL-001: which is a 25:1 Cannabidiol (CBD): ∆9-tetrahydrocannabidiol (THC) oral formulation with a concentration of 50 mg/ml of CBD and 2 mg/ml of THC. The starting dose will be 1 mL per day (50 mg CBD) orally and gradually titrated to a maximum dose of 6 mL (300 mg CBD) per day in a divided dosage within 6 to 8 weeks of treatment initiation based on patient assessment. Once the optimal dose has been determined, which maximizes potential therapeutic effects while minimizing adverse effects, the dose will be maintained for the remainder of the trial.
Other Name: CBD concentrate

Experimental: CBD+THC oil
Participants will receive CBD (cannabidiol) oil in combination with THC (delta-9-tetrahydrocannabinol) for a total duration of 12 weeks.
Drug: CDB+THC oil (MPL-005)
MPL-005: which is a 5:1 Cannabidiol (CBD):∆9-tetrahydrocannabidiol (THC) oral formulation with a concentration of 25 mg/ml of CBD and 5 mg/ml of THC. The starting dose will be 1 mL per day (25 mg CBD + 5 mg THC) orally and gradually titrated to a maximum dose of 6 mL (150 mg CBD + 30 mg THC) per day in a divided dosage within 6 to 8 weeks of treatment initiation based on patient assessment. Once the optimal dose has been determined, which maximizes potential therapeutic effects while minimizing adverse effects, the dose will be maintained for the remainder of the trial.
Other Name: CBD concentrate

Placebo Comparator: Placebo oil
Participants will receive matching placebo oil for a total duration of 12 weeks.
Drug: Placebo oil
The starting dose will be 1 mL per day (contains no API) orally and gradually titrated to a maximum dose of 6 mL per day in a divided dosage within 6 to 8 weeks of treatment initiation based on patient assessment. Once the optimal dose has been determined, which maximizes potential therapeutic effects while minimizing adverse effects, the dose will be maintained for the remainder of the trial.
Other Name: Matching placebo




Primary Outcome Measures :
  1. Feasibility outcome: pertaining to the patients recruitment [ Time Frame: Through study completion, an average of 1 year ]
    The ability to recruit the necessary number of patients during the estimated 6-month period

  2. Feasibility outcome: pertaining to adherence to intervention [ Time Frame: Up to 12 weeks post-treatment ]
    Defined as ≥70% of patients taking ≥70% of the prescribed doses and assessed from the participant-kept study drug diary data at each study visit.

  3. Feasibility outcome: pertaining to withdrawal from study [ Time Frame: Up to 12 weeks post-treatment ]
    Participant withdrawal from the study <20%

  4. Feasibility outcome: pertaining to questionnaire data [ Time Frame: Up to 12 weeks post-treatment ]
    The amount of missing data from all questionnaires <20%

  5. Feasibility outcome: the rate of unintentional unblinding [ Time Frame: Up to 12 weeks post-treatment ]
    Defined as the participant correctly identifying group allocation and blinding success will be quantified using the BANG Index.


Secondary Outcome Measures :
  1. The mean Morphine Equivalent (MEQ) dose (mg/day) at 12 weeks post-treatment [ Time Frame: Baseline and at 2-,4-,6-,8- and 12-weeks post-treatment ]
    The data for opioid consumption will be extracted from the medical record or obtained via self report. MEQ will be calculated based on the 2017 Canadian Guideline for Safe and Effective Use of Opioids for Chronic Non-Cancer Pain.

  2. The mean pain interference at 12 weeks post-treatment [ Time Frame: Baseline and at 2-,4-,6-,8- and 12-weeks post-treatment ]
    Pain interference will be assessed with The Patient Reported Outcomes Measurement Information System (PROMIS) Pain Interference - Short Form 8a scale. This validated scale consists of 8 items detailing the extent to which pain interferes with the individual's abilities to perform and enjoy daily life; each item is rated on a 5-point scale (1=not at all, 2=a little bit, 3=somewhat, 4=quite a bit and 5=very much). Scores are calculated from the total of item responses, with higher scores reflecting greater pain interference.


Other Outcome Measures:
  1. The proportion of patients weaned off opioids at 12 weeks post-treatment initiation [ Time Frame: 12-weeks post-treatment ]
    Defined as no opioid use on the day prior to the final study visit

  2. Mean pain severity scores at 12-weeks post-treatment [ Time Frame: Baseline and at 2-,4-,6-,8- and 12-weeks post-treatment ]
    Pain severity will be assessed with three separate numeric rating scales (NRS): pain now, pain at its maximum in the past 24 hours, and pain at its minimum in the past 24 hours. Each NRS will range from 0 "not at all severe" to 10 "pain as bad as you can imagine. Higher scores indicate greater pain severity.

  3. Overall improvement related to the intervention [ Time Frame: Baseline and at 2-,4-,6-,8- and 12-weeks post-treatment ]
    Overall improvement related to the intervention will be assessed with the Patient Global Impression of Change Scale (PGIC). PGIC is a single item rated on a 7-point scale from "very much improved" to "very much worse".

  4. Adverse events assessment [ Time Frame: Baseline and at 2-,4-,6-,8- and 12-weeks post-treatment ]
    Adverse events will be assessed with the Toronto Side Effects Scale (TSES), a measure of the incidence, frequency and severity of 31 adverse events plus an open-ended item.

  5. Assessment of symptoms of anxiety [ Time Frame: Baseline and at 12-weeks post-treatment ]
    The symptoms of anxiety will be measured using Generalized Anxiety Disorder 7-item scale (GAD-7). This 7-item scale assesses the signs of GAD (e.g. ''Feeling afraid as if something awful might happen") with response option of : 0= Not at all, 1=Several days, 2= More than half the days and 3= Nearly everyday. Scores are calculated from the total of item responses, with higher scores reflecting greater anxiety.

  6. Assessment of symptoms of depression [ Time Frame: Baseline and at 12-weeks post-treatment ]

    The symptoms of depression will be measured by Patient Health Questionnaire 9 item scale (PHQ-9).

    The PHQ-9 assesses the signs of depression (e.g. Little interest or pleasure in doing things) with response option of :

    0= Not at all, 1= Several days, 2= More than half the days, 3= Nearly everyday. Scores are calculated from the total of item responses, with higher scores reflecting the greater severity of depression.




Information from the National Library of Medicine

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Ages Eligible for Study:   25 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age ≥ 25 years
  2. Able to understand and read English
  3. Experiencing chronic, non-palliative pain
  4. Current daily opioid consumption ≥ 50 mg MEQ

Exclusion Criteria:

  1. Using nabilone, nabiximols or cannabis weekly for ≥ 12 weeks in the past year
  2. Known allergy to cannabis or any cannabinoid
  3. Diagnosed with a serious lung, liver, kidney or heart disease
  4. Have a personal or family history of serious mental disorders such as schizophrenia, psychosis, depression, or bipolar disorder
  5. Currently pregnant or breast-feeding (a negative urine pregnancy test must be obtained for women of child bearing potential during pretreatment evaluation)
  6. Men and women planning to start a family in the next 12 weeks
  7. Has declared a current alcohol or substance use disorder (excluding opioid use disorder)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05351905


Contacts
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Contact: Jo Carroll, RN 416-340-4800 ext 3243 jo.carroll@uhn.ca
Contact: Sonal Thaker 416-340-4800 ext 4251 Sonalben.thaker@uhnresearch.ca

Locations
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Canada, Ontario
University Health Network Recruiting
Toronto, Ontario, Canada, M5G 2C4
Contact: Sonalben Thaker    4163404800 ext 4251    sonalben.thaker@uhnresearch.ca   
Contact: Jo Carroll    4163404800 ext 3243    Jo.carroll@uhn.ca   
Sponsors and Collaborators
University Health Network, Toronto
Investigators
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Principal Investigator: Hance Clarke, MD, PhD Toronto General Hospital, UHN
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Responsible Party: Jo Carroll, Research Manager, University Health Network, Toronto
ClinicalTrials.gov Identifier: NCT05351905    
Other Study ID Numbers: 19-5944
First Posted: April 28, 2022    Key Record Dates
Last Update Posted: November 29, 2022
Last Verified: November 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Chronic Pain
Pain
Neurologic Manifestations