Clinical trial NCT05052541: Safety and Efficacy of Oral Cannabis in Chronic Spine Pain
Official title: Safety and Efficacy of Oral Cannabis in Chronic Spine Pain
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Back Pain
Neck Pain
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
Collaborators: name: Colorado Department of Public Health and Environment
First posted: 2021-09-22
Enrollment: 157
Sex: ALL
Minimum age (years): 21
Maximum age (years): 84
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: One Main Arm is Crossover (Analgesia Arm) One Main Arm is Parallel (Reduction Arm)
Primary purpose: TREATMENT

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.

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.

Eligibility 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.

Primary outcomes:
measure: Change in chronic pain as measured by the Visual Analog Scale (VAS) for pain
timeFrame: Weekly, up to week 22
measure: Change in opioid dose as measured in morphine milligram equivalents (MME)
timeFrame: Weekly, up to week 22
Secondary outcomes:
measure: Study Drug Tolerability as measured by study drug use
timeFrame: Daily, up to week 22
measure: Study Drug Tolerability as measured by side effects
timeFrame: Daily, up to week 22
measure: Change in spine-related disability and quality of life as measured on the NIH Patient Reported Outcomes Measurement System (PROMIS)-29
timeFrame: Weekly, up to week 22
measure: 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
timeFrame: Weekly, up to week 22
measure: Change in use of opioid and non-opioid analgesic medications
timeFrame: Daily, up to week 22
measure: Change in abuse liability of cannabis as measured on the Drug Effects Questionnaire (DEQ) for study drug (cannabis)
timeFrame: Weekly, up to week 22
measure: Change in abuse liability of cannabis as measured on a VAS for study drug (cannabis) craving
timeFrame: Weekly, up to week 22
measure: Change in opioid craving and withdrawal as measured on a VAS for opioid craving
timeFrame: Weekly, up to week 22
measure: Change in opioid craving and withdrawal as measured on the Subjective Opiate Withdrawal Scale (SOWS)
timeFrame: Weekly, up to week 22
measure: Change in opioid craving and withdrawal as measured on the Drug Effect Questionnaire (DEQ)
timeFrame: Weekly, up to week 22
measure: Change in opioid craving and withdrawal as measured on the Current Opioid Misuse Measure (COMM).
timeFrame: Weekly, up to week 22
measure: Change in pain sensitivity as measured by pain threshold (kPa) to a pressure stimulus
timeFrame: Weekly, up to week 22
measure: Change in cognition as assessed by the List Sorting Working Memory Test
timeFrame: Weeks 5, 13 and 21 (Analgesia Arm) Week 12 (Reduction Arm)
measure: Change in cognition as assessed by the Pattern Comparison Processing Speed Test
timeFrame: Weeks 5, 13 and 21 (Analgesia Arm) Week 12 (Reduction Arm)
measure: Change in cognition as assessed by the Oral Symbol Digit Test
timeFrame: Weeks 5, 13 and 21 (Analgesia Arm) Week 12 (Reduction Arm)
measure: Change in cognition as assessed by the Flanker Inhibitory Control and Attention Test
timeFrame: Weeks 5, 13 and 21 (Analgesia Arm) Week 12 (Reduction Arm)
measure: Change in cognition as assessed by the Picture Vocabulary Test
timeFrame: Weeks 5, 13 and 21 (Analgesia Arm) Week 12 (Reduction Arm)
measure: Change in cognition and motor skills as assessed by the Hopkins Verbal Learning Test Revised (HVLT-R)
timeFrame: Weeks 5, 13 and 21 (Analgesia Arm) Week 12 (Reduction Arm)
measure: Change in motor skills as assessed by the Grooved Pegboard Test
timeFrame: Weeks 5, 13 and 21 (Analgesia Arm) Week 12 (Reduction Arm)
measure: Change in motor skills as assessed by the Standardized Field Sobriety Test
timeFrame: Weeks 5, 13 and 21 (Analgesia Arm) Week 12 (Reduction Arm)
measure: Change in participant's perceived improvement in spine pain as measured on the Patient Global Impression of Change Scale (PGIC)
timeFrame: Weeks 5, 13 and 21 (Analgesia Arm) Week 12 (Reduction Arm)
Other outcomes:
measure: Change in 2-arachidonoylglycerol levels as measured in plasma
timeFrame: Baseline, Weeks 5, 13 and 21 (Analgesia Arm) Week 12 (Reduction Arm)
measure: Change in N-arachidonoylethanolamine levels as measured in plasma
timeFrame: Baseline, Weeks 5, 13 and 21 (Analgesia Arm) Week 12 (Reduction Arm)
measure: Change in tumor necrosis factor alpha (TNF-α) levels as measured in plasma
timeFrame: Baseline, Weeks 5, 13 and 21 (Analgesia Arm) Week 12 (Reduction Arm)
measure: Change in C-reactive protein (CRP) levels as measured in plasma
timeFrame: Baseline, Weeks 5, 13 and 21 (Analgesia Arm) Week 12 (Reduction Arm)
Locations:
city: Aurora
country: United States
facility: University of Colorado Anschutz Medical Campus
state: Colorado
Study officials:
affiliation: University of Colorado, Denver
name: Emily Lindley, PhD
role: PRINCIPAL_INVESTIGATOR
References: