Summary

Eligibility
for people ages 21 years and up (full criteria)
Location
at San Diego, California and other locations
Dates
study started
estimated completion

Description

Summary

Veterans with diabetes are more likely than diabetic civilians to develop disabling chronic diabetic neuropathic pain (CDNP). Research on frontline treatments for CDNP (enhanced glycemic control, exercise, pharmacological agents), 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 CDNP. 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 CDNP is vital. The present phase II study will offer the first evidence describing the potential benefits and adverse effects of cannabinoids for CDNP in Veterans using a four-arm, double-blind, multisite randomized trial comparing THC, CBD, THC+CBD and placebo on neuropathic pain outcomes.

Official Title

Proof of Concept Trial of Cannabis Derivatives in Neuropathic Pain.

Details

Chronic pain is a significant burden to United States Veterans and is a particular concern for Veterans with diabetes. Diabetic Veterans have a higher risk of chronic diabetic neuropathic pain (CDNP) than civilians with diabetes, and CDNP is more disabling for Veterans than it is for civilians. Frontline treatment for CDNP, including enhanced glycemic control, exercise, and pharmacotherapies, show inconsistent outcomes for individuals with CDNP due to poor adherence and 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 CDNP. The study is to recruit a sample of 320 adult Veterans who meet diagnostic criteria for high-impact CDNP, are on stable treatment(s) for CDNP, are not current cannabis users and who do not meet diagnostic criteria for Cannabis Use Disorder. After a 2-week single-blind placebo lead-in (SBPLI) to wash out part of the placebo response, eligible Veterans will be randomly assigned to one of four study arms: 1) 10 mg THC P.O ; 2) 800 mg CBD P.O ; 3) 10.8 mg THC + 10 mg CBD P.O ; or 4) placebo P.O , with an 8-week treatment including a 2-week titration phase (to minimize side effects and improve tolerability), then 4 weeks on the target treatment dose and a subsequent 2-week down titration (to minimize cannabis withdrawal symptoms). 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 CDNP. This trial will offer the first evidence describing the potential benefits and adverse effects of cannabinoids for CDNP in Veterans.

Keywords

Diabetic Neuropathic Pain Neuralgia Dronabinol Nabiximols THC (Dronabinol) CBD (Epidolex) THC + CBD (Nabiximols)

Eligibility

You can join if…

Open to people ages 21 years and up

  • Able to provide written consent
  • Veterans 21 years and older at the date of screening
  • Meet NEURODIAB criteria for painful diabetic peripheral neuropathy
  • Meet criteria for persistent, high-impact pain criteria.
  • Presence of allodynia confirmed by one of the screening dynamic brush tests

You CAN'T join if...

  • Primary source of pain not related to diabetic neuropathy
  • Hypersensitivity to THC, CBD, or THC/CBD
  • Positive urine toxicology for THC-COOH on 2 consecutive visits before and including baseline assessment
  • 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
  • Need for immediate psychiatric hospitalization
  • Enrolled in a medical marijuana program
  • Federal employee

Locations

  • VA San Diego Healthcare System, San Diego, CA
    San Diego California 92161 United States
  • VA Puget Sound Health Care System Seattle Division, Seattle, WA
    Seattle Washington 98108 United States

Details

Status
not yet accepting patients
Start Date
Completion Date
(estimated)
Sponsor
VA Office of Research and Development
ID
NCT05351801
Phase
Phase 2 research study
Study Type
Interventional
Participants
Expecting 320 study participants
Last Updated