Proof of Concept Trial of Cannabis Derivatives in Neuropathic Pain

NCT05351801 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: NURP-002-20F
• Study Type: interventional
• Target: 320
• Locations: 1 country
• Sites: 6

Brief Summary

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.

Conditions

Neuropathic Pain; Peripheral Neuropathic Pain

Outcome Measures

Primary Outcomes (1)

• To compare the short-term efficacy of THC, CBD, or THC+CBD vs Placebo on Neuropathic Pain as measured by the Numeric Rating Scale of Pain

  The mean change in the weekly average of daily Numeric Rating Scale (NRS) pain score (0-10 scale; 0=no pain, 10=worst possible pain) from baseline to week 6.

  Baseline, Week 6

Secondary Outcomes (11)

• To assess the efficacy of THC, CBD, or THC+CBD vs Placebo in pain quality (allodynia) as measured by the Quantitative Sensory Testing.

  Baseline, Week 2, Week 4, Week 6, Week 8

• To assess the efficacy of THC, CBD, or THC+CBD vs Placebo in disability and function as measured by the Neuropathic Pain Scale.

  Baseline, Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7, Week 8

• To assess the efficacy of THC, CBD, or THC+CBD vs Placebo in disability and function as measured by the Gait Speed Test

  Baseline, Week 4, Week 8

• To assess the efficacy of THC, CBD, or THC+CBD vs Placebo in mean changes in perceived improvement as measured by the Patient Global Impression of Change

  Baseline, Week 2, Week 4, Week 6, Week 8

• To assess the efficacy of THC, CBD, or THC+CBD vs Placebo in mean changes in perceived improvement as measured by the patient satisfaction visual analog scale.

  Baseline, Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7, Week 8

Study Arms (4)

THC (Syndros)

ACTIVE COMPARATOR

Target dose of 10mg per day.

Drug: THC (Syndros); Drug: Placebo

CBD (Epidolex)

ACTIVE COMPARATOR

Target dose of 800 mg per day.

Drug: CBD (Epidolex); Drug: Placebo

THC + CBD (Nabiximols)

ACTIVE COMPARATOR

Target dose of 10.8 mg / 10 mg per day.

Drug: THC + CBD (Nabiximols); Drug: Placebo

Placebo

PLACEBO COMPARATOR

Identical in appearance to the three active comparators.

Drug: Placebo

Interventions

THC (Syndros) DRUG

Participants will receive a target dose of 10mg per day of THC (Syndros).

THC (Syndros)

CBD (Epidolex) DRUG

Participants will receive a target dose of 800 mg per day of CBD (Epidolex).

CBD (Epidolex)

THC + CBD (Nabiximols) DRUG

Participants will receive a target dose of 10.8 mg / 10 mg per day of THC + CBD (Nabiximols).

THC + CBD (Nabiximols)

Placebo DRUG

Placebo

CBD (Epidolex); Placebo; THC (Syndros); THC + CBD (Nabiximols)

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• women of childbearing potential who agree to abide by contraceptive requirements

You may not qualify if:

• Actively engaged in or planning to enter a program of non-pharmacological invasive intervention for pain at the time of enrollment
• 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

Sponsors & Collaborators

• VA Office of Research and Development: lead

Study Sites (6)

VA San Diego Healthcare System, San Diego, CA

San Diego, California, 92161-0002, United States

RECRUITING

VA Greater Los Angeles Healthcare System, West Los Angeles, CA

West Los Angeles, California, 90073-1003, United States

ACTIVE NOT RECRUITING

VA Connecticut Healthcare System West Haven Campus, West Haven, CT

West Haven, Connecticut, 06516-2770, United States

RECRUITING

Providence VA Medical Center, Providence, RI

Providence, Rhode Island, 02908-4734, United States

RECRUITING

South Texas Health Care System, San Antonio, TX

San Antonio, Texas, 78229-4404, United States

RECRUITING

VA Puget Sound Health Care System Seattle Division, Seattle, WA

Seattle, Washington, 98108-1532, United States

TERMINATED

MeSH Terms

Conditions

Neuralgia

Interventions

Dronabinol; nabiximols

Condition Hierarchy (Ancestors)

Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cannabinoids; Terpenes; Hydrocarbons; Organic Chemicals

Study Officials

• Deepak D'Souza, MD MBBS

  VA Connecticut Healthcare System West Haven Campus, West Haven, CT

  PRINCIPAL INVESTIGATOR

• Donald McGeary, PhD

  South Texas Health Care System, San Antonio, TX

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Courtney C DiCocco

CONTACT

(203) 932-5711; Courtney.DiCocco@va.gov

Mohini Ranganathan, MD

CONTACT

(203) 932-5711; Mohini.Ranganathan@va.gov

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Model Details: Double-blind, randomized, placebo-controlled, parallel group Phase II study with randomization to one of the four treatment arms: 1) 10 mg mg THC , 2) 800 mg CBD , 3) 10.8 mg THC + 10 mg CBD , and 4) placebo. The 8-week treatment phase comprises a 2-week up-titration, 4 weeks maintenance on the target dose followed by 2 weeks down-titration, to minimize cannabis withdrawal syndrome. The two-weeks up titration phase is to minimize side effects and improve tolerability. Efficacy will be assessed by responses during the 4-week target dose phase.

Study Record Dates

• First Submitted: April 8, 2022
• First Posted: April 28, 2022
• Study Start: June 21, 2023
• Primary Completion (Estimated): September 29, 2028
• Study Completion (Estimated): May 31, 2029
• Last Updated: February 27, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)