Trial of Dronabinol and Vaporized Cannabis in Neuropathic Low Back Pain

Study Description

Brief Summary

Detailed Description

Condition or disease	Intervention/treatment	Phase
Cannabis Low Back Pain Neuropathic Pain	Drug: Placebos Other Names sugar pill Drug: dronabinol Other Names Marinol Drug: Vaporized Cannabis 3.7% THC/5.6% CBD Other Names marijuana	Phase 2

Tracking Information

First Submitted Date	May 29, 2015
Last Update Posted Date	September 16, 2017
Start Date	September 01, 2016
Anticipated Completion Date	May 01, 2020
Primary Completion Date	May 01, 2020
Results First Submitted Date	N/A
Received Results Disposit Date	N/A

Current Primary Outcome Measures

• Numerical Pain Intensity [Time Frame: 8 weeks]

  11-point pain intensity numerical rating scale (PI-NRS), where 0 equals no pain and 10 equals worst possible pain

Original Primary Outcome Measures

Current Secondary Outcome Measures

• Repeated Measures Recommended Minimal Dataset (NIH Task Force on chronic low back pain) [Time Frame: 8 weeks]

• Neuropathic Pain Scale [Time Frame: 8 weeks]

  11-point numerical scale consisting of 13 questions that ask ratings of various pain descriptors (e.g., pain intensity, sharpness, dullness)

• Hopkins Verbal Learning Test [Time Frame: 8 weeks]

• Grooved Pegboard Test [Time Frame: 8 weeks]

• Wechsler Adult Intelligence Scale-III Digit Symbol Test [Time Frame: 8 weeks]

• Profile of Mood States [Time Frame: 8 weeks]

  This questionnaire contains 65 words/statements that describe feelings people have. The test requires the patient to indicate for each word or statement how he or she has been feeling in the past week. There are 6 subscales: tension-anxiety (9 items, score range: 0-36), depression (15 items, range 0-60), anger-hostility (12 items, range 0-48), vigor-activity (8 items, range 0-32), fatigue (7 items, range 0-28), confusion-bewilderment (7 items, range 0-28) The total mood disturbance equals adding subscales and subtracting vigor (range 0-200)

• Beck Depression Inventory II [Time Frame: 8 weeks]

• Locally Developed Psychoactive Effect Scale [Time Frame: 8 weeks]

• Marijuana subscale (M-scale) of the Addiction Research Center Inventory [Time Frame: 8 weeks]

• Cold Pressor Test [Time Frame: 8 weeks]

• Cannabis Withdrawal Scale [Time Frame: 2 weeks]

• Driving Simulation (Lane Tracking and Car Following) [Time Frame: 8 hours]

  Lane Tracking: This task requires subjects to drive down a straight 2-lane road, maintain a constant speed of 55 mph, maintain appropriate lane position, and respond to divided attention tasks in the upper corners of the screen. The primary outcomes are standard deviation of lateral deviation (swerving). Car Following: This simulation examines the participant's ability to closely match the speed of an automobile in front of them. Participants are to follow a lead vehicle at a safe and constant distance. The primary outcomes is coherence between the participant and lead cars (a general correlation [0-1] of the participant's ability to accurately track the speed variations of the lead car.

Original Secondary Outcome Measures

Study Design

Brief Title	Trial of Dronabinol and Vaporized Cannabis in Neuropathic Low Back Pain
Official Title	A Randomized, Cross-Over Controlled Trial of Dronabinol and Vaporized Cannabis in Neuropathic Low Back Pain
Brief Summary	This study will involve treating low back pain associated with nerve injury with oral delta-9-tetrahydrocannabinol (Δ9-THC) or whole plant cannabis for eight weeks. Research subjects will consume either oral Δ9-THC (dronabinol), vaporized 3.7% Δ9-THC/5.6% CBD, or placebo. An analysis will then be determined to assess the risk--benefit ratio of dronabinol and vaporized 3.7% Δ9-THC/5.6% CBD .
Detailed Description	The present study is designed to assess whether treatment with vaporized cannabis or dronabinol (oral Δ9-THC) reduces spontaneous and evoked pain more than placebo, and whether there are any differences between the two active treatments in terms of interference with activities of daily living. This study also aims to examine the effects of vaporized whole plant cannabis and dronabinol on mood, neuropsychological function, and psychomimetic side-effects (high, stoned, etc.) compared to placebo and to each other. In addition, we plan to examine the acute effects (after receiving stable treatment for 4 weeks) of vaporized cannabis and dronabinol compared to placebo and each other on driving skills.
Study Type	Interventional
Study Phase	Phase 2
Estimated Enrollment	120
Allocation	Randomized
Interventional Model	Parallel Assignment
Masking	Triple
Primary Purpose	Treatment
Conditions	Cannabis Low Back Pain Neuropathic Pain
Target Follow-Up Duration	N/A
Biospecimen:	N/A
Sampling Method	N/A
Study Population	N/A
Intervention	Drug: Placebos Administration of vaporized cannabis plus either dronabinol or placebo pill Other Names sugar pill Drug: dronabinol Administration of vaporized cannabis plus either dronabinol or placebo pill Other Names Marinol Drug: Vaporized Cannabis 3.7% THC/5.6% CBD Administration of vaporized cannabis plus either dronabinol or placebo pill Other Names marijuana
Study Groups/Cohorts	Placebos The present study is designed to evaluate whether or not a medium dose of cannabis (3.7% delta-9-THC/5.6% CBD) can maintain an analgesic response over an eight week period compared to placebo. Dronabinol A direct comparison of cannabis and dronabinol has not been performed in a clinical population. The present study will fill this void by performing a randomized, controlled 8 week trial comparing the effectiveness of oral versus vaporized cannabis in patients with neuropathic low back pain. Vaporized Cannabis 3.7% THC/5.6% CBD The eight week outpatient study will compare the efficacy and side effect profile of cannabis (3.7%THC/5.6%CBD) and dronabinol. We will also perform a human laboratory experiment evaluating driving using the same study medications that subjects received during their 8 week outpatient treatment.
Study Arms	Active Comparator Dronabinol A direct comparison of cannabis and dronabinol has not been performed in a clinical population. The present study will fill this void by performing a randomized, controlled 8 week trial comparing the effectiveness of oral versus vaporized cannabis in patients with neuropathic low back pain. Drug : dronabinol Administration of vaporized cannabis plus either dronabinol or placebo pill Placebo Comparator Placebos The present study is designed to evaluate whether or not a medium dose of cannabis (3.7% delta-9-THC/5.6% CBD) can maintain an analgesic response over an eight week period compared to placebo. Drug : Placebos Administration of vaporized cannabis plus either dronabinol or placebo pill Experimental Vaporized Cannabis 3.7% THC/5.6% CBD The eight week outpatient study will compare the efficacy and side effect profile of cannabis (3.7%THC/5.6%CBD) and dronabinol. We will also perform a human laboratory experiment evaluating driving using the same study medications that subjects received during their 8 week outpatient treatment. Drug : Vaporized Cannabis 3.7% THC/5.6% CBD Administration of vaporized cannabis plus either dronabinol or placebo pill

Arm	Intervention/Treatment
Active Comparator Dronabinol A direct comparison of cannabis and dronabinol has not been performed in a clinical population. The present study will fill this void by performing a randomized, controlled 8 week trial comparing the effectiveness of oral versus vaporized cannabis in patients with neuropathic low back pain.	Drug : dronabinol Administration of vaporized cannabis plus either dronabinol or placebo pill
Placebo Comparator Placebos The present study is designed to evaluate whether or not a medium dose of cannabis (3.7% delta-9-THC/5.6% CBD) can maintain an analgesic response over an eight week period compared to placebo.	Drug : Placebos Administration of vaporized cannabis plus either dronabinol or placebo pill
Experimental Vaporized Cannabis 3.7% THC/5.6% CBD The eight week outpatient study will compare the efficacy and side effect profile of cannabis (3.7%THC/5.6%CBD) and dronabinol. We will also perform a human laboratory experiment evaluating driving using the same study medications that subjects received during their 8 week outpatient treatment.	Drug : Vaporized Cannabis 3.7% THC/5.6% CBD Administration of vaporized cannabis plus either dronabinol or placebo pill

Recruitment Information

Recruitment Status:	Recruiting
Enrollment	120
Completion Date	May 01, 2020
Eligibility Criteria:	Inclusion Criteria: Age greater than 18. Presence of chronic low back pain (CLBP) defined as the response to two questions 1) How long has back pain been an ongoing problem for you? 2) How often has low back pain been an ongoing problem for you over the past 6 months? A response of greater than 3 months to question 1 and a response of "at least half the days in the past 6 months" to question 2 will define CLBP according to the NIH Task Force on Research Standards for Chronic Low Back Pain. The numerical pain intensity must be greater than 3/10 each day during the one-week observation period. To avoid confounding by concurrent medications, participants will have had a stable analgesic regimen that they will continue throughout the study To obviate residual neuropsychological effects from cannabis exposure, participants will be abstinent from this herbal medicine for 7 days prior to study entry. Exclusion Criteria: Presence of another painful condition of greater severity than the neuropathic pain condition which is being studied. History of traumatic brain injury. Clinically significant or unstable medical condition. Individuals with significant cardiovascular, hepatic or renal disease, uncontrolled hypertension, and chronic pulmonary disease (eg, asthma, COPD), will be excluded. If warranted clinically, subjects will undergo laboratory evaluation (blood chemistry, electrocardiogram, urinalysis, toxicology screening for confirmation. Females of childbearing potential will undergo pregnancy testing. A positive result on toxicity screening will exclude individuals from participation. A urine drug test that screens for 5 categories of drugs: marijuana (Δ9-THC), cocaine, amphetamines/methamphetamines, opiates, benzodiazepines and phencyclidine (PCP) will be employed. A positive result for opioids and/or THC will not be exclusionary if the patient is receiving a prescription for an opioid and/or THC. Allergy to sesame oil, lactose, or gelatin Vascular disease, especially Raynauld's syndrome, systolic blood pressure > 170 mm, diastolic blood pressure > 100 mm Recent injuries to the upper extremity Cognitive impairment, such as Dementia or Alzheimer's Disease Substance Abuse History: The Substance Abuse Module of the Diagnostic Interview Schedule for DSM-IV will be administered to exclude individuals with current substance use disorders. Pregnancy as ascertained by a mandatory commercial pregnancy test Past history of suicide attempt. Cannabis can exacerbate pre-existing schizophrenia, and has been linked to an increase in the risk of suicide in such patients. In patients with bipolar disorder, cannabis use has been associated with worsening of manic and psychotic symptoms. Such findings suggest that cannabis is contraindicated in individuals with serious mental health issues, a line of reasoning that will be observed in the present study by excluding patients in the bipolar/schizoaffective/schizophrenic spectrum. Suicidality. Exposure to cannabis does not lead to depression but it may be associated with suicidal thoughts and attempts. Therefore, the BDI-II will be used to measure suicidal ideation.
Gender	All
Age	19 Years to 70 Years
Accepts Healthy Volunteers	No
Contacts	Barth L Wilsey, MD (619) 543-5000 [email protected]
Listed Location Countries	United States

Administrative Information

NCT Number:	NCT02460692
Other Study ID Numbers	1R01DA038634-01A1 R01DA038634
Has Data Monitoring Committee	Yes
U.S. FDA-regulated Product	Studies a U.S. FDA-regulated Drug Product: No Studies a U.S. FDA-regulated Device Product: No Device Product Not Approved or Cleared by U.S. FDA: No
IPD Sharing Statement	Not Available
Responsible Party	Barth Wilsey MD, University of California, San Diego
Study Sponsor	University of California, San Diego
Collaborators	National Institute on Drug Abuse (NIDA)
Investigators	Principal Investigator Barth L Wilsey, MD UC San Diego