Safety and Efficacy of Oral Cannabis in Chronic Spine Pain
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 157
- 试验地点
- 1
- 主要终点
- Change in chronic pain as measured by the Visual Analog Scale (VAS) for pain
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 21 Years 至 84 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Some inclusion/
排除标准
- •are purposely omitted at this time to preserve scientific integrity. They will be included after the trial is complete.
- •Inclusion Criteria:
- •Self-reported 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
- •Any medical condition for which immunosuppressive therapy is required.
- •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.
研究组 & 干预措施
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.
干预措施: THC/CBD (Drug)
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.
干预措施: THC (Drug)
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.
干预措施: Placebo (Drug)
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.
干预措施: THC/CBD (Drug)
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.
干预措施: THC (Drug)
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.
干预措施: Placebo (Drug)
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.
干预措施: THC/CBD (Drug)
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.
干预措施: THC (Drug)
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.
干预措施: Placebo (Drug)
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.
干预措施: THC/CBD (Drug)
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.
干预措施: THC (Drug)
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.
干预措施: Placebo (Drug)
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.
干预措施: THC/CBD (Drug)
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.
干预措施: THC (Drug)
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.
干预措施: Placebo (Drug)
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.
干预措施: THC/CBD (Drug)
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.
干预措施: THC (Drug)
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.
干预措施: Placebo (Drug)
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.
干预措施: THC/CBD (Drug)
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.
干预措施: Placebo (Drug)
结局指标
主要结局
Change in chronic pain as measured by the Visual Analog Scale (VAS) for pain
时间窗: 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".
Change in opioid dose as measured in morphine milligram equivalents (MME)
时间窗: Weekly, up to week 22
次要结局
- Change in cognition as assessed by the Pattern Comparison Processing Speed Test(Weeks 5, 13 and 21 (Analgesia Arm) Week 12 (Reduction Arm))
- Study Drug Tolerability as measured by study drug use(Daily, up to week 22)
- Study Drug Tolerability as measured by side effects(Daily, up to week 22)
- Change in abuse liability of cannabis as measured on a VAS for study drug (cannabis) craving(Weekly, up to week 22)
- Change in pain sensitivity as measured by pain threshold (kPa) to a pressure stimulus(Weekly, up to week 22)
- Change in cognition as assessed by the List Sorting Working Memory Test(Weeks 5, 13 and 21 (Analgesia Arm) Week 12 (Reduction Arm))
- Change in spine-related disability and quality of life as measured on the NIH Patient Reported Outcomes Measurement System (PROMIS)-29(Weekly, up to week 22)
- Change in use of opioid and non-opioid analgesic medications(Daily, up to week 22)
- 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(Weekly, up to week 22)
- Change in abuse liability of cannabis as measured on the Drug Effects Questionnaire (DEQ) for study drug (cannabis)(Weekly, up to week 22)
- Change in opioid craving and withdrawal as measured on the Subjective Opiate Withdrawal Scale (SOWS)(Weekly, up to week 22)
- Change in opioid craving and withdrawal as measured on a VAS for opioid craving(Weekly, up to week 22)
- Change in opioid craving and withdrawal as measured on the Drug Effect Questionnaire (DEQ)(Weekly, up to week 22)
- Change in opioid craving and withdrawal as measured on the Current Opioid Misuse Measure (COMM).(Weekly, up to week 22)
- Change in cognition and motor skills as assessed by the Hopkins Verbal Learning Test Revised (HVLT-R)(Weeks 5, 13 and 21 (Analgesia Arm) Week 12 (Reduction Arm))
- Change in cognition as assessed by the Oral Symbol Digit Test(Weeks 5, 13 and 21 (Analgesia Arm) Week 12 (Reduction Arm))
- Change in cognition as assessed by the Flanker Inhibitory Control and Attention Test(Weeks 5, 13 and 21 (Analgesia Arm) Week 12 (Reduction Arm))
- Change in cognition as assessed by the Picture Vocabulary Test(Weeks 5, 13 and 21 (Analgesia Arm) Week 12 (Reduction Arm))
- Change in motor skills as assessed by the Grooved Pegboard Test(Weeks 5, 13 and 21 (Analgesia Arm) Week 12 (Reduction Arm))
- Change in motor skills as assessed by the Standardized Field Sobriety Test(Weeks 5, 13 and 21 (Analgesia Arm) Week 12 (Reduction Arm))
- Change in participant's perceived improvement in spine pain as measured on the Patient Global Impression of Change Scale (PGIC)(Weeks 5, 13 and 21 (Analgesia Arm) Week 12 (Reduction Arm))