Topical Cannabis for Chronic Musculoskeletal Pain

Not yet recruiting

• Conditions: Chronic Pain; Musculoskeletal Pain; Joint Pain

• Registration Number: NCT05908552
• Lead Sponsor: University of Colorado, Denver

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2023-01-17
• Status Verified: 2023-06
• Study First Submitted QC: 2023-06-09
• Last Update Submitted: 2023-06-09
• Study First Posted: 2023-06-18
• Last Update Posted: 2023-06-18
• Study Start: 2023-07-01
• Primary Completion: 2024-04-30
• Study Completion: 2024-08-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 77

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

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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

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Levels of plasma cannabinoid and cannabinoid metabolites	Baseline to 2 weeks	Four venous blood samples will be obtained at baseline, 4 hours, 24 hours, and 2 weeks after first use of the selected topical cannabinoid.
Change in in PROMIS Pain Interference Score from Baseline to 2 months	Assessed at baseline, 4 hours, 24 hours, 2 weeks and 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.

Secondary Outcome Measures

Name	Time	Method
Reported drug effects	Baseline, 4 hours, 24 hours, 2 weeks, 2 months	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
Change in in PROMIS Pain Intensity Score from Baseline to 2 months	Assessed at baseline, 4 hours, 24 hours, 2 weeks and 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).
Change in Patient-Reported Outcomes Measurement Information System (PROMIS)-29 Profile from Baseline to 2 months	Assessed at baseline, 4 hours, 24 hours, 2 weeks and 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.
Change in Patients' Global Impression of Change (PGIC) from Baseline to 2 Months	Assessed at baseline, 4 hours, 24 hours, 2 weeks and 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."
Opioid and non-opioid pain medications use	Daily through 2 weeks	Participant self-report of opioid and non-opioid analgesic use
Change in NIH Toolbox® List Sorting Working Memory Test from Baseline to 2 Weeks	Assessed at baseline, 4 hours, 24 hours, 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.
Change in NIH Toolbox® Oral Symbol Digit Test from Baseline to 2 Weeks	Assessed at baseline, 4 hours, 24 hours, 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.
Change in Fine Motor Function from Baseline to 2 Weeks	Assessed at baseline, 4 hours, 24 hours, 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.
Change in Gross Motor Function from Baseline to 2 Weeks	Assessed at baseline, 4 hours, 24 hours, 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.
Change Patient Specific Functional Scale from Baseline to 2 Months	Assessed at baseline, 4 hours, 24 hours, 2 weeks and 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.
Change in NIH Toolbox® Picture Vocabulary Test from Baseline to 2 Weeks	Assessed at baseline, 4 hours, 24 hours, 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.
Abuse liability	Assessed at baseline, 4 hours, 24 hours, 2 weeks and 2 months	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
Participant Treatment Expectations and Impressions	Assessed at baseline, 4 hours, 24 hours, 2 weeks and 2 months	Questionnaires will be conducted to assess participants' treatment expectations and impressions.
Participant Perceived Efficacy	Assessed at baseline, 4 hours, 24 hours, 2 weeks and 2 months	Questionnaires will be conducted to assess participants' impressions of perceived efficacy of the chosen topical cannabinoid.
Participant Preference vs Other Analgesics	Assessed at baseline, 4 hours, 24 hours, 2 weeks and 2 months	Questionnaires will be conducted to assess participants' preference for the chosen topical cannabinoid vs other analgesics.
Participant Reported Adverse Effects	Assessed at baseline, 4 hours, 24 hours, 2 weeks and 2 months	Questionnaires will be conducted to assess participants' reported Adverse Effects
Change in NIH Toolbox® Flanker Inhibitory Control and Attention Test from Baseline to 2 Weeks	Assessed at baseline, 4 hours, 24 hours, 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.
Change in NIH Toolbox® Pattern Comparison Processing Speed Test from Baseline to 2 Weeks	Assessed at baseline, 4 hours, 24 hours, 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.
Half life analysis of cannabinoid and cannabinoid metabolites	baseline through 2 weeks	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.
Clearance analysis of cannabinoid and cannabinoid metabolites	baseline through 2 weeks	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.
Volume of distribution analysis of cannabinoid and cannabinoid metabolites	baseline through 2 weeks	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.