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Safety and Efficacy of Oral Cannabis in Chronic Spine Pain

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05052541
Recruitment Status : Not yet recruiting
First Posted : September 22, 2021
Last Update Posted : May 18, 2022
Sponsor:
Collaborator:
Colorado Department of Public Health and Environment
Information provided by (Responsible Party):
University of Colorado, Denver

Brief Summary:
The overall objectives of this study are to investigate the efficacy of extended cannabis treatment to reduce patient exposure to prescription opioids through its use 1) as a non-opioid analgesic treatment, and 2) as a therapy for reducing high-dose opioid use in patients with chronic spine pain.

Condition or disease Intervention/treatment Phase
Back Pain Neck Pain Drug: THC/CBD Drug: THC Drug: Placebo Phase 3

Detailed Description:
This randomized, placebo-controlled clinical trial is designed to elucidate the role of extended oral cannabis treatment in the alleviation of chronic spine pain and reduction of high-dose opioid use. This trial includes two study arms: Analgesia Arm and Reduction Arm. The Analgesia Arm uses a within-subject crossover design to determine whether daily treatment with an oral cannabis solution for 6 weeks significantly reduces spine pain compared to placebo. The Reduction Arm uses a parallel design to determine whether daily treatment with an oral cannabis solution for 13 weeks results in a greater reduction of pain and opioid intake than placebo treatment. It will also assess the impact of extended cannabis treatment on opioid craving and symptoms of opioid withdrawal in participants tapering their high-dose opioids.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 157 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description: One Main Arm is Crossover (Analgesia Arm) One Main Arm is Parallel (Reduction Arm)
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Safety and Efficacy of Oral Cannabis in Chronic Spine Pain
Estimated Study Start Date : July 2022
Estimated Primary Completion Date : June 2024
Estimated Study Completion Date : June 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Marijuana

Arm Intervention/treatment
Experimental: Analgesia Arm: THC (tetrahydrocannabinol), then THC/CBD (cannabidiol), then Placebo
Subjects in this crossover arm will be assigned to 6 weeks on THC oral solution, then 6 weeks on THC/CBD oral solution, then 6 weeks on Placebo oral solution. Frequency of drug administration is 3-4 times a day.
Drug: THC/CBD
Oral solution containing 5mg THC and 50 mg CBD per 1 ml

Drug: THC
Oral solution containing 5mg THC per 1 ml

Drug: Placebo
Oral solution containing no active drug

Experimental: Analgesia Arm: THC, then Placebo, then THC/CBD
Subjects in this crossover arm will be assigned to 6 weeks on THC oral solution, then 6 weeks on Placebo oral solution, then 6 weeks on THC/CBD oral solution. Frequency of drug administration is 3-4 times a day.
Drug: THC/CBD
Oral solution containing 5mg THC and 50 mg CBD per 1 ml

Drug: THC
Oral solution containing 5mg THC per 1 ml

Drug: Placebo
Oral solution containing no active drug

Experimental: Analgesia Arm: THC/CBD, then THC, then Placebo
Subjects in this crossover arm will be assigned to 6 weeks on THC/CBD oral solution, then 6 weeks on THC oral solution, then 6 weeks on Placebo oral solution. Frequency of drug administration is 3-4 times a day.
Drug: THC/CBD
Oral solution containing 5mg THC and 50 mg CBD per 1 ml

Drug: THC
Oral solution containing 5mg THC per 1 ml

Drug: Placebo
Oral solution containing no active drug

Experimental: Analgesia Arm: THC/CBD, then Placebo, then THC
Subjects in this crossover arm will be assigned to 6 weeks on THC/CBD oral solution, then 6 weeks on Placebo oral solution, then 6 weeks on THC oral solution. Frequency of drug administration is 3-4 times a day.
Drug: THC/CBD
Oral solution containing 5mg THC and 50 mg CBD per 1 ml

Drug: THC
Oral solution containing 5mg THC per 1 ml

Drug: Placebo
Oral solution containing no active drug

Experimental: Analgesia Arm: Placebo, then THC, then THC/CBD
Subjects in this crossover arm will be assigned to 6 weeks on Placebo oral solution, then 6 weeks on THC oral solution, then 6 weeks on THC/CBD oral solution. Frequency of drug administration is 3-4 times a day.
Drug: THC/CBD
Oral solution containing 5mg THC and 50 mg CBD per 1 ml

Drug: THC
Oral solution containing 5mg THC per 1 ml

Drug: Placebo
Oral solution containing no active drug

Experimental: Analgesia Arm: Placebo, then THC/CBD, then THC
Subjects in this crossover arm will be assigned to 6 weeks on Placebo oral solution, then 6 weeks on THC/CBD oral solution, then 6 weeks on THC oral solution. Frequency of drug administration is 3-4 times a day.
Drug: THC/CBD
Oral solution containing 5mg THC and 50 mg CBD per 1 ml

Drug: THC
Oral solution containing 5mg THC per 1 ml

Drug: Placebo
Oral solution containing no active drug

Experimental: Reduction Arm: THC/CBD
Subjects in this parallel arm will be assigned to 13 weeks on THC/CBD oral solution. Frequency of drug administration is 3-4 times a day.
Drug: THC/CBD
Oral solution containing 5mg THC and 50 mg CBD per 1 ml

Placebo Comparator: Reduction Arm: Placebo
Subjects in this parallel arm will be assigned to 13 weeks on Placebo oral solution. Frequency of drug administration is 3-4 times a day.
Drug: Placebo
Oral solution containing no active drug




Primary Outcome Measures :
  1. Change in chronic pain as measured by the Visual Analog Scale (VAS) for pain [ Time Frame: Weekly, up to week 22 ]
    The Visual Analog Scale (VAS) for pain is a 0-100mm visual scale anchored by "no pain" and "worst possible pain".

  2. Change in opioid dose as measured in morphine milligram equivalents (MME) [ Time Frame: Weekly, up to week 22 ]

Secondary Outcome Measures :
  1. Study Drug Tolerability as measured by study drug use [ Time Frame: Daily, up to week 22 ]
    study drug dose, frequency

  2. Study Drug Tolerability as measured by side effects [ Time Frame: Daily, up to week 22 ]
  3. Change in spine-related disability and quality of life as measured on the NIH Patient Reported Outcomes Measurement System (PROMIS)-29 [ Time Frame: Weekly, up to week 22 ]
    The NIH Patient Reported Outcomes Measurement System (PROMIS)-29 is a collection of 4-item short forms assessing anxiety, depression, fatigue, pain interference, physical function, sleep disturbance, and ability to participate in social roles and activities as well as a single pain intensity item.

  4. Change in spine-related disability and quality of life as measured on the NIH Task Force on Research Standards for Chronic Low-Back/Neck Pain Minimal Dataset [ Time Frame: Weekly, up to week 22 ]
    The NIH Task Force on Research Standards for Chronic Low-Back Pain Minimal Dataset (and the modified Dataset for neck pain) assesses the influence of back/neck pain on physical function, emotional health, sleep, everyday activities.

  5. Change in use of opioid and non-opioid analgesic medications [ Time Frame: Daily, up to week 22 ]
  6. Change in abuse liability of cannabis as measured on the Drug Effects Questionnaire (DEQ) for study drug (cannabis) [ Time Frame: Weekly, up to week 22 ]
    The Drug Effects Questionnaire (DEQ) for study drug (cannabis) assesses the subjective effects after taking a drugs, including feeling a drug effect, liking/disliking the drug effect, feeling high, and wanting more drug.

  7. Change in abuse liability of cannabis as measured on a VAS for study drug (cannabis) craving [ Time Frame: Weekly, up to week 22 ]
    The VAS for study drug (cannabis) craving is a 100 mm visual scale anchored by "not at all" and "extremely" when asked about drug craving in the past week

  8. Change in opioid craving and withdrawal as measured on a VAS for opioid craving [ Time Frame: Weekly, up to week 22 ]
    The VAS for opioid craving is a 100 mm visual scale anchored by "not at all" and "extremely" when asked about opioid craving in the past week.

  9. Change in opioid craving and withdrawal as measured on the Subjective Opiate Withdrawal Scale (SOWS) [ Time Frame: Weekly, up to week 22 ]
    The Subjective Opiate Withdrawal Scale (SOWS) is a self-report questionnaire containing 16 symptoms related to opioid withdrawal.

  10. Change in opioid craving and withdrawal as measured on the Drug Effect Questionnaire (DEQ) [ Time Frame: Weekly, up to week 22 ]
    The Drug Effects Questionnaire (DEQ) for opioids assesses the subjective effects after taking opioids, including feeling a drug effect, liking/disliking the drug effect, feeling high, and wanting more opioids.

  11. Change in opioid craving and withdrawal as measured on the Current Opioid Misuse Measure (COMM). [ Time Frame: Weekly, up to week 22 ]
    Current Opioid Misuse Measure (COMM) is a brief patient self-assessment to help identify participants who exhibit aberrant behaviors associated with the misuse of opioid medications.

  12. Change in pain sensitivity as measured by pain threshold (kPa) to a pressure stimulus [ Time Frame: Weekly, up to week 22 ]
    Pressure output on a computer-controlled pressure algometer will be set to 10 kPa/s and participants will be instructed to indicate when the sensation changes from one of pressure alone to one of pressure and pain (pain threshold) by pressing a button on the remote-control indicator

  13. Change in cognition as assessed by the List Sorting Working Memory Test [ Time Frame: Weeks 5, 13 and 21 (Analgesia Arm) Week 12 (Reduction Arm) ]
    The List Sorting Working Memory Test measures attention/working memory. Participants recall and sequence different visually and orally presented stimuli (e.g., participants are asked to list a set of given animals in order by size, from smallest to largest).

  14. Change in cognition as assessed by the Pattern Comparison Processing Speed Test [ Time Frame: Weeks 5, 13 and 21 (Analgesia Arm) Week 12 (Reduction Arm) ]
    The Pattern Comparison Processing Speed Test is a measure of processing speed. Participants discern whether two side-by-side pictures are the same or not, with 85 seconds to respond to as many items as possible.

  15. Change in cognition as assessed by the Oral Symbol Digit Test [ Time Frame: Weeks 5, 13 and 21 (Analgesia Arm) Week 12 (Reduction Arm) ]
    The Oral Symbol Digit Test is a measure of processing speed. Symbols on the screen are associated with a number in a key. Participants are then presented symbols without numbers. Participants say each number that goes with each presented symbol for 90 seconds.

  16. Change in cognition as assessed by the Flanker Inhibitory Control and Attention Test [ Time Frame: Weeks 5, 13 and 21 (Analgesia Arm) Week 12 (Reduction Arm) ]
    The Flanker Inhibitory Control and Attention Test measures attention and inhibitory control. Participants are required to indicate the left-right orientation of a centrally presented stimulus while inhibiting attention to the potentially incongruent stimuli that surround it (i.e., the flankers, two on either side).

  17. Change in cognition as assessed by the Picture Vocabulary Test [ Time Frame: Weeks 5, 13 and 21 (Analgesia Arm) Week 12 (Reduction Arm) ]
    The Picture Vocabulary Test measures receptive vocabulary. Respondents select pictures (from arrays) that most closely match the meanings of presented words.

  18. Change in cognition and motor skills as assessed by the Hopkins Verbal Learning Test Revised (HVLT-R) [ Time Frame: Weeks 5, 13 and 21 (Analgesia Arm) Week 12 (Reduction Arm) ]
    The HVLT-R is a measure of verbal learning and memory. Participants are asked to learn a 12-item word list over three trials (total immediate learning). A delayed free recall trial is administered after 20 minutes, followed by a yes/no recognition trial.

  19. Change in motor skills as assessed by the Grooved Pegboard Test [ Time Frame: Weeks 5, 13 and 21 (Analgesia Arm) Week 12 (Reduction Arm) ]
    The Grooved Pegboard is a test of fine motor coordination and speed. In this test, participants place 25 small metal pegs into holes on a 3"x3" metal board as quickly as possible. All pegs are alike and have a ridge on 1 side that corresponds to a randomly oriented notch in each hole on the metal board.

  20. Change in motor skills as assessed by the Standardized Field Sobriety Test [ Time Frame: Weeks 5, 13 and 21 (Analgesia Arm) Week 12 (Reduction Arm) ]
    The Standardized Field Sobriety Test is intended to detect driving impairments due to recent alcohol or drug use.

  21. Change in participant's perceived improvement in spine pain as measured on the Patient Global Impression of Change Scale (PGIC) [ Time Frame: Weeks 5, 13 and 21 (Analgesia Arm) Week 12 (Reduction Arm) ]
    The Patient Global Impression of Change Scale (PGIC) is a 7-point scale depicting a patient's rating of overall improvement.


Other Outcome Measures:
  1. Change in 2-arachidonoylglycerol levels as measured in plasma [ Time Frame: Baseline, Weeks 5, 13 and 21 (Analgesia Arm) Week 12 (Reduction Arm) ]
    2-arachidonoylglycerol will be measured in pmol/ml

  2. Change in N-arachidonoylethanolamine levels as measured in plasma [ Time Frame: Baseline, Weeks 5, 13 and 21 (Analgesia Arm) Week 12 (Reduction Arm) ]
    N-arachidonoylethanolamine will be measured in pmol/ml

  3. Change in tumor necrosis factor alpha (TNF-α) levels as measured in plasma [ Time Frame: Baseline, Weeks 5, 13 and 21 (Analgesia Arm) Week 12 (Reduction Arm) ]
    TNF-α will be measured in pg/ml

  4. Change in C-reactive protein (CRP) levels as measured in plasma [ Time Frame: Baseline, Weeks 5, 13 and 21 (Analgesia Arm) Week 12 (Reduction Arm) ]
    CRP will be measured in mg/L



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   21 Years to 84 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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:

Documented chronic (≥3 months' duration), non-radicular spine pain

Exclusion Criteria:

Unwilling/unable to refrain from cannabis use (medical or recreational) for 14 days prior to Baseline Visit and throughout the study (other than study drug). This includes whole plant inhalation, edibles, extracts, and topicals.

Co-morbid cancer-related pain condition

Neuropathic Pain

A co-morbid pain condition that is of greater severity than the patient's spine pain

Spine or other major surgery within the 3 months prior to enrollment

Planned surgery or procedural intervention during the study period

Allergy or adverse reaction to cannabis

Current or historical substance use disorder

Current or historical alcohol use disorder

Current or prior cannabis abuse/dependence

Positive result for use of amphetamine/methamphetamine, barbiturates, benzodiazepines, cocaine, phencyclidine (PCP), ecstasy (MDMA), as detected on urine screen

Current use of valproate, clobazam, clopidogrel, warfarin, barbiturates, benzodiazepines

Prior adverse reaction to cannabis exposure (paranoia, anxiety, etc.)

History or diagnosis of schizophrenia, bipolar or a psychotic disorder

History of any mental health illness that in the opinion of the Investigator would compromise the safety of the participant

Current or historical severe depression

Current suicidal ideation

Diagnosed cognitive impairment (e.g. Alzheimer's Disease, traumatic brain injury)

Uncontrolled hypertension (>139/89)

Abnormal values on CBC (complete blood count) or CMP (comprehensive metabolic panel) laboratory analysis that are deemed clinically significant by study physician

Known hepatic disease or dysfunction, or identification of such on screening laboratory studies

Known cardiovascular disease

Abnormal result on electrocardiogram (ECG) that is deemed clinically significant by study MD

Cognitive disability that interferes with ability to provide consent or understand study procedure

History of seizure disorder

Diagnosed autoimmune or rheumatological disease such as rheumatoid arthritis (RA) or multiple sclerosis (MS)

Inability to refrain from using tobacco for at least 4 hours

Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the participant or the quality of the data

Pending legal action or workers compensation

Pregnant females or females intending to become pregnant during the study period

Unwilling to use one of the accepted forms of contraception during the study period and for at least 60 days after completion of the study (females of childbearing potential and males with sexual partners of childbearing potential)

Lactating females

Analgesia Arm Exclusion Criteria:

Unwilling/unable to discontinue current opioid use for 14 days prior to Baseline study visit and throughout the study

Reduction Arm Exclusion Criteria:

Not interested in reducing or discontinuing use of prescribed opioids for chronic pain

Unwilling to allow the study team to communicate with the participant's opioid prescribing provider

*Some inclusion/exclusion criteria are purposely omitted at this time to preserve scientific integrity. They will be included after the trial is complete.


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): NCT05052541


Contacts
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Contact: Rahwa Netsanet, BS 303-724-0923 mjpainstudy@ucdenver.edu

Locations
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United States, Colorado
University of Colorado Anschutz Medical Campus
Aurora, Colorado, United States, 80045
Contact: Emily Lindley, PhD    303-724-0239    MJPainStudy@ucdenver.edu   
Principal Investigator: Rachael Rzasa Lynn, MD         
Sponsors and Collaborators
University of Colorado, Denver
Colorado Department of Public Health and Environment
Investigators
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Principal Investigator: Emily Lindley, PhD University of Colorado, Denver
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Responsible Party: University of Colorado, Denver
ClinicalTrials.gov Identifier: NCT05052541    
Other Study ID Numbers: 20-0701
First Posted: September 22, 2021    Key Record Dates
Last Update Posted: May 18, 2022
Last Verified: May 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Neck Pain
Pain
Neurologic Manifestations
Dronabinol
Hallucinogens
Physiological Effects of Drugs
Psychotropic Drugs
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Cannabinoid Receptor Agonists
Cannabinoid Receptor Modulators
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists