Dronabinol as an Adjunct for Reducing Pain — DARP  

Chronic Pain Clinical Trial

Official title: A Randomized, Double-Blind, Placebo-Controlled, Parallel Groups Study to Explore the Safety and Therapeutic Potential of Dronabinol as an Adjunct for Reducing Pain

Status Recruiting

Clinical Trial Summary

This exploratory, proof-of-concept study is a double-blind (participants and investigators will be blinded), placebo-controlled, randomized, two-arm clinical trial of Marinol [dronabinol, synthetic Δ9-tetrahydrocannabinol (THC)] for chronic low back pain (cLBP) with a 2:1 allocation ratio. Up to 75 subjects will be enrolled in this pilot study and randomized to receive doses of THC (up to 30 mg/day), orally, over 8 weeks. This study will be conducted at a single site; it does not include any stratifications, and there is no interim analysis planned. Notably, the goal is to determine whether there is enough evidence of the safety of THC to support the development of later-phase clinical trials. Thus, detailed developmental plans are contingent on the outcomes of this study.

Clinical Trial Description

Musculoskeletal pain can be due to an injury to the bones, joints, muscles, tendons, ligaments, or nerves, which can be caused by jerking movements, car accidents, falls, fractures, sprains, dislocations, and direct blows to the muscle. Musculoskeletal pain can be localized in one area, or widespread. Lower back pain is the most common type of musculoskeletal pain. Other common types include tendonitis, myalgia (muscle pain), and stress fractures. A review of opioids for non-cancer musculoskeletal diseases concluded that opioids were "only slightly more effective than their placebos, no more effective than acetaminophen, and somewhat less effective than nonsteroidal anti-inflammatory drugs. In fact, the Centers for Disease Control (CDC) recommends that opioids should not be considered an option for chronic musculoskeletal pain. The impact of cannabinoid treatments on pain in human volunteers has been evaluated for: 1) experimentally induced acute pain, 2) acute postsurgical pain, and 3) chronic pain. Collectively, these data suggest that cannabinoids may be more effective for chronic rather than acute pain conditions. However, there have been few randomized, double-blind, placebo-controlled clinical trials (RCTs, the "Gold Standard" in intervention-based studies) of cannabinoids for pain. To this end, the proposed study will contribute to the evidence base concerning the potential utility of treating chronic low back pain (cLBP) with cannabinoids.

Four RCTs in 159 patients with fibromyalgia, osteoarthritis, chronic back pain, and rheumatoid arthritis treated with oral cannabinoids (nabilone, THC/cannabidiol (CBD), and fatty acid amide hydrolase (FAAH) inhibitor, placebo, or active control (amitriptyline), were included in a systemic review. The results were inconsistent and did not reveal whether the cannabinoids were superior to the controls (placebo and amitriptyline). The authors concluded that there is insufficient evidence for the recommendation for cannabinoid use for pain management in patients with rheumatic diseases. Since then, a Phase II RCT (65 participants) found no difference between THC and placebo in reducing pain measures in patients with chronic abdominal pain due to surgery or chronic pancreatitis.

A more recent systematic review and meta-analysis aimed to "analyze the evidence surrounding the benefits and harms of medical cannabinoids in the treatment of chronic, non-cancer-related pain". Thirty-six trials (4006 participants) were included, examining smoked cannabis (4 trials), oromucosal cannabis sprays (14 trials), and oral cannabinoids (18 trials). Of the 18 trials that examined oral cannabinoids, 15 examined synthetic THC in the form of dronabinol (n=9), nabilone (n=4), or nasimol (n=2). Treatment durations ranged from 1 day to 6 months. Across the 29 trials (34 comparisons) that had reported on pain outcomes, there was a significant treatment effect favoring the use of cannabinoids over placebo (-0.63, 95% confidence interval (CI), -0.85 to -0.42, I2 = 16%, P < 0.00001). Compared with placebo, cannabinoids showed a significant reduction in pain, which was greatest with treatment duration of 2 to 8 weeks (weighted mean difference on a 0-10 pain visual analog scale -0.68, 95% CI, -0.96 to -0.40, I2 = 8%, P < 0.00001; n = 16 trials). Across all time points, oral formulations demonstrated a superior effect compared with oromucosal and inhaled routes of administration. Serious AEs were rare, and similar across the cannabinoid (74 out of 2176, 3.4%) and placebo groups (53 out of 1640, 3.2%). There was an increased risk of non-serious adverse events (AEs) with cannabinoids compared with placebo. Overall, the authors found that cannabinoids are an effective form of pain control in this patient population, with a particularly strong effect among those cannabinoids that are orally administered. However, these studies were found to be limited by overall quality, which were largely underpowered, selective, and inconsistent in their reporting. This preliminary evidence of effectiveness indicates the need for high-quality RCTs in orthopedic areas.

The FDA has not approved a cannabinoid medication to treat cLBP. Here the investigators propose to study the effects of THC for several reasons. First, although both smoked cannabis and THC decrease pain sensitivity, increase pain tolerance, and decrease subjective ratings of pain intensity, THC produces more consistent analgesia for a longer duration. Second, the therapeutic effects of cannabinoids are best established for THC. Third, defined substances, such as purified cannabinoid compounds, are preferable to plant products, which are of variable and uncertain composition. Use of defined cannabinoids permits a more precise evaluation of their effects, whether combined or alone. Finally, compared with marijuana, THC produces lower ratings of abuse-related subjective effects, which can be predictive of use and abuse patterns. Hence, the investigators have elected to study THC. The primary objective of this double-blind, randomized, placebo-controlled, 1-site study is to explore the safety and tolerability of THC, versus placebo when orally administered to patients suffering from chronic pain. ;

Related Conditions & MeSH terms

• Back Injuries
• Chronic Pain
• Low Back Pain

• NCT number: NCT06454669
• Study type: Interventional
• Source: Baylor College of Medicine
• Contact: Christopher D Verrico, PhD
• Phone: 713-791-1414
• Email: verrico@bcm.edu
• Status: Recruiting
• Phase: Phase 2
• Start date: June 15, 2024
• Completion date: December 31, 2027