Proof of Concept Trial of Cannabis Derivatives in Neuropathic Pain

VA Office of Research and Development

Status and phase: Enrolling; Phase 2

Conditions: Peripheral Neuropathic Pain; Diabetic Neuropathic Pain

Treatments: Drug: CBD (Epidolex); Drug: THC + CBD (Nabiximols); Drug: THC (Syndros); Drug: Placebo

Study type: Interventional

Funder types: Other U.S. Federal agency

Identifiers

NCT05351801

NURP-002-20F

Details and patient eligibility

About

Chronic neuropathic pain (CNP) is disabling. Research on frontline treatments for CNP, shows inconsistent outcomes and dissatisfaction among Veterans. Veterans and clinicians have shown significant interest in cannabis derivatives (THC, CBD) for neuropathic pain control, but there are no well-controlled trials guiding expectations for benefit and adverse outcomes associated with cannabis for CNP. Because Veterans are likely to present with pain and pain-related polymorbidity significantly differing from that of civilians, a well-structured clinical trial of cannabinoids for Veterans with CNP is vital.

Full description

Chronic pain is a significant burden to United States Veterans and is a particular concern for Veterans. One of the causes of pain is chronic neuropathic pain (CNP). Frontline treatment for CNP, show inconsistent outcomes and have significant side effects. The ongoing opioid crisis has led to significant interest in safe and effective alternatives for pain control, and there is a significant need for research on desirable options for pain control that are likely to improve treatment adherence and outcomes. Veterans groups and Veterans Affairs clinicians have expressed significant interest in cannabis and its principal constituents (delta-9-tetrahydrocannabinol, THC; cannabidiol, CBD) for pain management, but the extant research describing the potential risks and benefits of cannabis for pain is weak. This randomized trial was developed as a proof of concept study to determine if cannabis constituents (THC, CBD, and THC+CBD) are superior to placebo in reducing pain in Veterans with CNP. The study is to recruit a sample of 320 adult Veterans who meet diagnostic criteria for high-impact CNP, are on stable treatment(s) for CNP, are not current cannabis users and who do not meet diagnostic criteria for Cannabis Use Disorder. This randomized phase II, 4-arm clinical trial aims to determine if cannabis constituents (THC, CBD) or their combination (THC+CBD) are superior to placebo in reducing pain in Veterans with CNP. This trial will offer the first evidence describing the potential benefits and adverse effects of cannabinoids for CNP in Veterans.

Enrollment: 320 estimated patients

Sex: All

Ages: 21+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Able to provide written consent
• Veterans 21 years and older at the date of screening
• Meet diagnostic criteria for neuropathic pain as defined by the Neuropathic Pain Special Interest Group of the International Association for the Study of Pain (NeuPSIG)
• Meet criteria for persistent, high-impact pain criteria.
• Presence of allodynia confirmed by one of the screening dynamic brush tests

Exclusion criteria

• Peripheral neuropathy is not a primary source of neuropathic pain
• Hypersensitivity to THC, CBD, or THC/CBD
• Self-report of cannabis use during screening phase confirmed by positive urine toxicology for THC-COOH as measured and resulted at visit 5 before randomization
• Unwilling to refrain from using cannabis or cannabis-based products through the entire duration of the study
• Diagnosis of DSM-5 Cannabis Use Disorder in the past 6 months
• Current DSM-5 diagnosis of cannabis use disorder, substance use disorder or serious psychiatric disorders
• Actual change or intent to change is greater than a 20% change (increase or decrease) in any other medication for pain or non-pharmacological treatment from 4 weeks before the screening appointment until completion of study (i.e., visit 13)
• Opioid doses > 400 mg MME (morphine milligram equivalent)
• Women who are pregnant or breastfeeding, or who intend to become pregnant in the 12 weeks from enrollment
• Any current unstable or concerning medical condition that would place the patient at increased risk, including hepatic, respiratory, immunological, cardiovascular, endocrine, or renal disease, or in the opinion of the investigator, prevents adherence with the protocol
• Need for immediate psychiatric hospitalization
• Enrolled in a medical marijuana program
• Federal employee

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

320 participants in 4 patient groups, including a placebo group

THC (Syndros)

Active Comparator group

Description:

Target dose of 10mg per day.

Treatment:

Drug: Placebo

Drug: THC (Syndros)

CBD (Epidolex)

Active Comparator group

Description:

Target dose of 800 mg per day.

Treatment:

Drug: Placebo

Drug: CBD (Epidolex)

THC + CBD (Nabiximols)

Active Comparator group

Description:

Target dose of 10.8 mg / 10 mg per day.

Treatment:

Drug: Placebo

Drug: THC + CBD (Nabiximols)

Placebo

Placebo Comparator group

Description:

Identical in appearance to the three active comparators.

Treatment:

Drug: Placebo