Trial Outcomes & Findings for Trial of Dronabinol and Vaporized Cannabis in Chronic Low Back Pain (NCT NCT02460692)

Trial of Dronabinol and Vaporized Cannabis in Chronic Low Back Pain

The primary outcome is self-reported daily average numerical pain intensity during the past 24 hours. The numerical pain intensity is an 11-point pain intensity numerical rating scale (PI-NRS), where 0 equals no pain and 10 equals worst possible pain. The time frame includes baseline and weeks 1, 3, 5, 7, 8. Baseline is the pain tensity reported at the first day in the daily diary, before the first dose. The follow-up pain intensities (weeks 1, 3, 5, 7, 8) are the daily diary average pain intensities since the previously reported timepoint.

A Task Force was convened by the NIH Pain Consortium, with the goal of developing research standards for chronic low back pain. The results included recommendations for a repeated measures dataset in order to establish greater consistency in reporting in order to facilitate comparisons among studies. The repeated measure minimal dataset is based upon scores based upon the Patient-Reported Outcomes Measurement Information System ® (PROMIS). These items yield a classification of impacts on the lives of patients that range from 1 (least impact) to 42 (greatest impact).

The Neuropathic Pain Scale (NPS) is an 11-point numerical scale consisting of 13 questions that ask ratings of various pain descriptors (including pain intensity, sharpness, burning, aching, cold, sensitivity, itching,unpleasantness, deep, and surface pain). The NPS is scored as the sum of these pain descriptors. Range of scores is from 0 to100. A higher score is a worse score.

The Hopkins Verbal Learning Test provides information on the ability to learn and immediately recall verbal information across trials, as well at the ability to retain, reproduce, and recognize this information after a delay. A list of 12 words is presented to the subject over three trials. After each trial, the subject is to recall as many items as possible from the list in any desired order. A 20-minute delay follows the administration of the three trials, after which the subject is asked to recall the list. The ability to learn is represented by the number of correct words, with a score range of 0-36. A higher score indicates better performance.

The Grooved Pegboard Test is a test of fine motor coordination and speed. Subjects are required to place 25 small metal pegs into holes on a 3" x 3" metal board. All pegs are alike and have a ridge on one side, which corresponds to a notch in each hole on the board. First the dominant hand is tested, and subjects are asked to place the pegs in the holes as fast as they can. This is then repeated with the non-dominant hand, and the total time for each hand is recorded. A higher score indicates worse performance.

The Digit Symbol test measures concentration, psychomotor speed, and graphomotor abilities. This pen and paper test involves having subjects substitute a series of symbols with numbers as quickly and accurately as possible during a 120 second period. The results are expressed as the number of correct substitutions with a score range of 0-133. A higher number indicates better performance.

This questionnaire contains 65 words/statements that describe feelings people have. The questionnaire 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 (TMD) is calculated by adding the scores for tension-anxiety, depression, anger-hostility, fatigue and confusion-bewilderment and then subtracting the score for vigor-activity. The TMD is reported and has a score range of -32 to 200. A higher score indicates worse symptoms.

The Beck Depression Inventory is composed of items relating to symptoms of depression such as hopelessness and irritability, cognitions such as guilt or feelings of being punished, as well as physical symptoms such as fatigue, weight loss, and lack of interest in sex. Range of scores is from 0 to 63. A higher score is a worse score.

Visual Analogue Scale (VAS) ratings will be presented as a 100-mm horizontal line, anchored on the left with 'not at all' and on the right with 'extremely'. Participants will pencil in a vertical line along the horizontal line that represents their current feeling (questions usually phrased, 'During the past week, did you feel \_\_\_after consuming the vaporized cannabis?'). Ratings will be: any drug effect, a good drug effect, a bad drug effect, high, drunk, impaired, stoned, as if you liked the drug effect, sedated, confused, nauseous, like you desired more of the drug, anxious, down, and very hungry. This is a substudy. A good drug effect is presented. Range of scores is from 0 to 100. A higher score is a worse score.

The Marijuana subscale (M-scale) of the Addiction Research Center Inventory consists of 12 true or false questions corresponding to symptoms of cannabis intoxication; the minimum and maximum scores are 0 and 12 respectively. A higher score indicates a worse score. The questions were rephrased to evaluate the experience from the past week rather than an acute response to cannabis.

Each Cold Pressure Test will begin with an immersion of the left hand into a warm water bath for 3 min. During this time, blood pressure and heart rate will be measured. After removal of the hand from the warm water, skin temperature of the thumbpad will be recorded and participants will listen to a standardized script describing the procedures. Participants will then immerse the left hand into the cold water bath, and will be instructed to report the first painful sensation after immersion. They will then be asked to tolerate the stimulus as long as possible, but will be permitted to withdraw their hand from the cold water at any point. Maximum immersion time will be 2 min. Latency to first feel pain (pain sensitivity) and latency to withdraw the hand from the water (pain tolerance) will be recorded. Blood pressure and heart rate will be measured before and after each immersion using the arm that was not immersed in the water bath.

The Cannabis Withdrawal Scale is an assessment tool used to quantify the presence and intensity of various withdrawal symptoms (e.g., strange dreams, mood swings, depression, lack of appetite, and an inability to get to sleep). Range of scores for withdrawal intensity is from 0 to 190. A higher score is a worse score.

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 outcome is standard deviation of lateral deviation (swerving) with a score range of 0.51 - 3.24. A higher score indicates worse performance. The driving simulation assessments are conducted in a substudy, which only includes completers with a valid driver's license and who agreed to participate in the substudy.

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 outcome 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. A higher score indicates worse performance. The driving simulation assessments are conducted in a substudy, which only includes completers with a valid driver's license and who agreed to participate in the substudy.

A total of 15 separate VAS ratings will be presented as a 100-mm horizontal line, anchored on the left with 'not at all' and on the right with 'extremely'. Participants will pencil in a vertical line along the horizontal line that represents their current feeling (questions usually phrased, 'During the past week, did you feel \_\_\_after consuming the vaporized cannabis?'). Ratings will be: any drug effect, a good drug effect, a bad drug effect, high, drunk, impaired, stoned, as if you liked the drug effect, sedated, confused, nauseous, like you desired more of the drug, anxious, down, and very hungry. This is a substudy. Drug "high" will be presented. Range of scores is from 0 to 100. A higher score is a worse score.

The Cannabis Withdrawal Scale is an assessment tool used to quantify the presence and intensity of various withdrawal symptoms (e.g., strange dreams, mood swings, depression, lack of appetite, and an inability to get to sleep). The outcome is measured during the tapering period (weeks 8 and 10), at which patients slowly withdrew from medication over two weeks. Range of scores for the negative impact of withdrawal is from 0 to 190. A higher score is a worse score.

Each Cold Pressure Test will begin with an immersion of the left hand into a warm water bath for 3 min. During this time, blood pressure and heart rate will be measured. After removal of the hand from the warm water, skin temperature of the thumbpad will be recorded and participants will listen to a standardized script describing the procedures. Participants will then immerse the left hand into the cold water bath, and will be instructed to report the first painful sensation after immersion. They will then be asked to tolerate the stimulus as long as possible, but will be permitted to withdraw their hand from the cold water at any point. Maximum immersion time will be 2 min. Latency to first feel pain (pain sensitivity) and latency to withdraw the hand from the water (pain tolerance) will be recorded. Blood pressure and heart rate will be measured before and after each immersion using the arm that was not immersed in the water bath.