Topical Cannabis for Chronic Musculoskeletal Pain

Study Overview
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Brief Summary
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Our proposal objective is to evaluate if state-regulated topical CBD-based products relieve chronic musculoskeletal pain and/or absorb into the bloodstream.

Detailed Description
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The goal of this study is to learn more about the analgesic efficacy of state-regulated topical cannabinoid products (creams, lotions, salves, etc) and to determine if these topical products are absorbed systemically and can be detected in blood samples. Given that state-regulated dispensary products cannot be brought onto the university campus, this observational study design utilizes a Mobile Pharmacology Laboratory that will go to study participants' homes. Blood samples and other assessments will taken in the mobile lab prior to use of a topical cannabinoid product and at several time points afterwards (4 hours, 24 hours, and 2 weeks). Participants will also collect microsamples of blood using a small device at home at three time points during the first 2-72 hours after application of the product.

Official Title
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A Novel Non-Opioid Topical Therapy for Chronic Musculoskeletal Pain

Conditions
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Chronic Pain, Musculoskeletal Pain, Joint Pain

Participation Criteria
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Eligibility Criteria
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Some inclusion/exclusion criteria are purposely omitted at this time to preserve scientific integrity. They will be included after the trial is complete. Inclusion Criteria: Chronic peripheral joint pain Desire and intent to use a topical cannabinoid product containing cannabidiol (CBD) or a combination of CBD and tetrahydrocannabinol (THC) to alleviate this pain Exclusion Criteria: Current or prior use of topical cannabis Unwilling or unable to discontinue other (non-topical) cannabis use for four weeks prior to and during study participation through week two Intent to use a THC-predominant topical product (ratio greater than 1:1 of THC to CBD) Current or history of substance use disorder History or diagnosis of schizophrenia, bipolar or a psychotic disorder Surgery on the affected musculoskeletal location within the 3 months prior to enrollment Planned surgery or procedure on the affected musculoskeletal location during participation in the study Allergy or prior severe adverse reaction to cannabis (cardiovascular event, psychosis, etc) Current or prior cannabis abuse/dependence Cognitive disability that interferes with ability to provide consent or understand study procedures History of seizure disorder Pending legal action or workers compensation Pregnant females or females intending to become pregnant during the study period Lactating females Chronic/severe medical illness (renal disease, liver disease, cancer, significant cardiovascular disease, or history of myocardial infarction) Active component military

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 85 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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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in in PROMIS Pain Interference Score from Baseline to 2 months | The PROMIS Pain Interference (Short Form 6a) includes 6 items that assess the self-reported consequences of pain on various aspects of life including social, cognitive, emotional, physical and recreational activities. Participants rate these consequences on a Likert Scale that ranges from 1 (Not at all) to 5 (Very much). The scores are then converted to T-scores, with higher values indicating greater pain interference. | Assessed at baseline, 4 hours, 24 hours, 2 weeks and 2 months | 
| Levels of plasma cannabinoid and cannabinoid metabolites | Four venous blood samples will be obtained at baseline, 4 hours, 24 hours, and 2 weeks after first use of the selected topical cannabinoid. | Baseline to 2 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Opioid and non-opioid pain medications use | Participant self-report of opioid and non-opioid analgesic use | Daily through 2 weeks | 
| Reported drug effects | Subjective ratings of psychoactive effects (high,'' ''impaired,'' ''stoned,'' ''like the drug effect,'' ''sedated,'' ''confused,'' ''nauseated,'' ''desire more of the drug,'' ''anxious,'' ''down,'' ''hungry,'') measured on a 100-mm VAS | Baseline, 4 hours, 24 hours, 2 weeks, 2 months | 
| Change in in PROMIS Pain Intensity Score from Baseline to 2 months | The PROMIS Pain Intensity (Short Form 3a) includes 3 items that assess how much a person hurts. The first two items assess pain intensity using a 7-day recall period (items include the phrase the past 7 days) while the last item asks patients to rate their pain intensity right now. Participants rate their pain on a Likert Scale that ranges from: 1 (Had no pain) to 5 (Very severe). | Assessed at baseline, 4 hours, 24 hours, 2 weeks and 2 months | 
| Change in Patient-Reported Outcomes Measurement Information System (PROMIS)-29 Profile from Baseline to 2 months | The PROMIS-29 Profile assesses physiological, social, and psychological outcomes using a comprehensive set of biopsychosocial domains. These domains include physical function, anxiety, depression, fatigue, sleep, ability to participate in social roles and/or activities, pain interference, and pain intensity. The questionnaire responses are ranked on a 5-point Likert Scale, and pain intensity is rated on an 11-point scale. Higher scores reflect a greater presence of the measured domain. For symptom-oriented domains (anxiety, depression, fatigue, pain interference, and sleep disturbance), higher scores indicate more severe symptomatology, while for function-oriented domains (physical functioning and social role), higher scores indicate better functioning. For instance, a high sleep disturbance score indicates significant levels of sleep disruption, whereas a high physical functioning score indicates better physical capabilities. | Assessed at baseline, 4 hours, 24 hours, 2 weeks and 2 months | 
| Change in Patients' Global Impression of Change (PGIC) from Baseline to 2 Months | The Patient Global Impression of Change (PGIC) is a self-report measure used in chronic pain clinical trials to assess a patient's perception of treatment efficacy. The PGIC uses a 7-point scale where patients rate their overall improvement, ranging from very much improved to very much worse. | Assessed at baseline, 4 hours, 24 hours, 2 weeks and 2 months | 
| Change Patient Specific Functional Scale from Baseline to 2 Months | The Patient Specific Functional Scale is an 11-point scale where 0 represents unable to perform activity and 10 represents Able to perform activity at the same level as before injury or problem. Participants rate their ability to perform up to five important activities that they find difficult due to their musculoskeletal pain. | Assessed at baseline, 4 hours, 24 hours, 2 weeks and 2 months | 
| Change in NIH Toolbox® List Sorting Working Memory Test from Baseline to 2 Weeks | Test of working memory - the capacity of an individual to hold information in a short-term buffer and manipulate the information. All cognitive data will be represented by raw scores and T scores. We will assess changes over time in patients comparing their 4 hour, 24 hour, 2 week time-points to baseline. | Assessed at baseline, 4 hours, 24 hours, 2 weeks | 
| Change in NIH Toolbox® Oral Symbol Digit Test from Baseline to 2 Weeks | Test of processing speed - the amount of time it takes to mentally process a set amount of information, or the amount of information that can be processed within a certain unit of time. It is a measure that reflects mental efficiency. All cognitive data will be represented by raw scores and T scores. We will assess changes over time in patients comparing their 4 hour, 24 hour, 2 week time-points to baseline. | Assessed at baseline, 4 hours, 24 hours, 2 weeks | 
| Change in NIH Toolbox® Flanker Inhibitory Control and Attention Test from Baseline to 2 Weeks | Test of executive function - the capacity to plan, organize and monitor the execution of behaviors that are strategically directed in a goal-oriented manner) and attention (allocation of one's limited capacities to deal with an abundance of environmental stimulation) test. All cognitive data will be represented by raw scores and T scores. We will assess changes over time in patients comparing their 4 hour, 24 hour, 2 week time-points to baseline. | Assessed at baseline, 4 hours, 24 hours, 2 weeks | 
| Change in NIH Toolbox® Pattern Comparison Processing Speed Test from Baseline to 2 Weeks | Test of processing speed - the amount of time it takes to mentally process a set amount of information, or the amount of information that can be processed within a certain unit of time. It is a measure that reflects mental efficiency. All cognitive data will be represented by raw scores and T scores. We will assess changes over time in patients comparing their 4 hour, 24 hour, 2 week time-points to baseline. | Assessed at baseline, 4 hours, 24 hours, 2 weeks | 
| Change in NIH Toolbox® Picture Vocabulary Test from Baseline to 2 Weeks | Test of vocabulary knowledge. All cognitive data will be represented by raw scores and T scores. We will assess changes over time in patients comparing their 4 hour, 24 hour, 2 week time-points to baseline. | Assessed at baseline, 4 hours, 24 hours, 2 weeks | 
| Change in Fine Motor Function from Baseline to 2 Weeks | The Grooved Pegboard Test will be used to test fine motor function. The manipulative dexterity test described in the protocol consists of a board with twenty-five holes containing randomly positioned slots and pegs. The pegs have a key along one side and must be rotated to match the corresponding hole before insertion. This test evaluates the speed of performance in a fine motor task and assesses both sides of the body. | Assessed at baseline, 4 hours, 24 hours, 2 weeks | 
| Change in Gross Motor Function from Baseline to 2 Weeks | Change in Gross Motor Function will be assessed by the DRiving Under the Influence of Drugs (DRUID)® tests and Components of the Field Sobriety Tests, including One-Leg Stand, Walk-and-Turn, Modified Romberg Balance. The DRUID® tests measure impairment based on performance of various tasks. Scores range from 0-100, where lower scores indicate better performance. ≥13-point change (from baseline) on DRUID global impairment score = impaired; <13-point change (from baseline) = not impaired. Two or more clues noted during the field sobriety tests indicate impairment. | Assessed at baseline, 4 hours, 24 hours, 2 weeks | 
| Abuse liability | Craving visual analog scale (VAS): Assesses craving for topical cannabinoid on a 100mm visual scale. Drug Effects Questionnaire (DEQ): Assesses the strength of the topical cannabinoid effect | Assessed at baseline, 4 hours, 24 hours, 2 weeks and 2 months | 
| Participant Treatment Expectations and Impressions | Questionnaires will be conducted to assess participants' treatment expectations and impressions. | Assessed at baseline, 4 hours, 24 hours, 2 weeks and 2 months | 
| Participant Perceived Efficacy | Questionnaires will be conducted to assess participants' impressions of perceived efficacy of the chosen topical cannabinoid. | Assessed at baseline, 4 hours, 24 hours, 2 weeks and 2 months | 
| Participant Preference vs Other Analgesics | Questionnaires will be conducted to assess participants' preference for the chosen topical cannabinoid vs other analgesics. | Assessed at baseline, 4 hours, 24 hours, 2 weeks and 2 months | 
| Participant Reported Adverse Effects | Questionnaires will be conducted to assess participants' reported Adverse Effects | Assessed at baseline, 4 hours, 24 hours, 2 weeks and 2 months | 
| Half life analysis of cannabinoid and cannabinoid metabolites | A total of six blood samples will be obtained and analyzed using population pharmacokinetic modeling with sparse sampling with cannabinoids and their kinetically distinct metabolites. | baseline through 2 weeks | 
| Clearance analysis of cannabinoid and cannabinoid metabolites | A total of six blood samples will be obtained and analyzed using population pharmacokinetic modeling with sparse sampling with cannabinoids and their kinetically distinct metabolites. | baseline through 2 weeks | 
| Volume of distribution analysis of cannabinoid and cannabinoid metabolites | A total of six blood samples will be obtained and analyzed using population pharmacokinetic modeling with sparse sampling with cannabinoids and their kinetically distinct metabolites. | baseline through 2 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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topical, cannabis