Cannabinoids and an Anti-inflammatory Diet for the Treatment of Neuropathic Pain After Spinal Cord Injury

NCT04057456 | Completed Phase 3

• 1 other identifier: 6465
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

Neuropathic pain is a common complication following spinal cord injury (SCI) that significantly decreases quality of life. Treatment options are limited, and current treatments can have significant side effects. Those with SCI have identified a need for additional treatment options, particularly those that are not medications. Nabilone and an anti-inflammatory diet are two treatments that may provide pain relief while being better tolerated. This study will evaluate the benefits of these treatments for neuropathic pain after SCI. Study participants will receive either an anti-inflammatory diet or a placebo diet, and nabilone or a placebo for 4 weeks. It is expected that an anti-inflammatory diet and nabilone will significantly decrease pain intensity and improve function. The combination of both treatments together is expected to have a greater effect than each alone.

Conditions

Spinal Cord Injuries; Neuropathic Pain

Keywords

Nabilone; Spinal Cord Injury; Neuropathic pain; Pain; Anti Inflammatory Diet

Outcome Measures

Primary Outcomes (3)

• Average pain intensity

  Change from baseline to end of study in average pain intensity evaluated using the Numeric Rating Scale, which measures pain using a scale of 1-10 (1 being mild, and 10 being severe)

  Baseline and 9 weeks

• Sensory changes

  Changes from baseline to end of study in the items on the Neuropathic Pain Questionnaire

  Baseline and 9 weeks

• Pain relief

  Proportion of participants achieving at least 30% and 50% pain relief between treatments.

  Baseline and 9 weeks

Secondary Outcomes (8)

• Patient global impression of change

  Baseline and 9 weeks

• Financial feasibility of following anti-inflammatory diet

  9 weeks

• Mood Centre for Epidemiologic Studies-Depression scale

  Baseline and 9 weeks

• Sleep

  Baseline and 9 weeks

• Spasticity

  Baseline and 9 weeks

Study Arms (4)

Placebo diet and placebo capsules

PLACEBO COMPARATOR

Participants taking the placebo diet and capsules

Other: Placebo diet; Other: Placebo capsules

Placebo diet and Nabilone capsules

ACTIVE COMPARATOR

Capsules will be 0.5mg nabilone. Participants will take up to 8 capsules per day for a maximum dose of 4mg of nabilone per day.

Other: Placebo diet; Drug: Nabilone Capsules

Anti-inflammatory diet and placebo capsules

ACTIVE COMPARATOR

This meal plan will eliminate foods that have been established as pro-inflammatory (e.g. processed foods, refined sugars, refined wheat products, etc.) as well as foods that are commonly associated with even mild intolerances (e.g. cow's milk) and those that negatively impact cardiovascular health (e.g. hydrogenated oils, alcohol, coffee, refined sugars and wheat, trans fats, processed foods). In their place, the meal plan will consist of foods with established anti-inflammatory properties (e.g. (Oily fish, lean poultry, dark leafy greens, cruciferous vegetables, nuts, whole grains, most kinds of berries, etc).

Other: Anti-inflammatory diet; Other: Placebo capsules

Anti-inflammatory diet and Nabilone capsules

ACTIVE COMPARATOR

Capsules will be 0.5mg nabilone. Participants will take up to 8 capsules per day for a maximum dose of 4mg of nabilone per day. This meal plan will eliminate foods that have been established as pro-inflammatory (e.g. processed foods, refined sugars, refined wheat products, etc.) as well as foods that are commonly associated with even mild intolerances (e.g. cow's milk) and those that negatively impact cardiovascular health (e.g. hydrogenated oils, alcohol, coffee, refined sugars and wheat, trans fats, processed foods). In their place, the meal plan will consist of foods with established anti-inflammatory properties (e.g. (Oily fish, lean poultry, dark leafy greens, cruciferous vegetables, nuts, whole grains, most kinds of berries, etc).

Other: Anti-inflammatory diet; Drug: Nabilone Capsules

Interventions

Placebo diet OTHER

The dietitian will assist in developing a diet that is isocaloric to the anti-inflammatory diet and healthy (for the sake of the participants' well-being, and to blind participants), while allowing many foods that are (counterintuitively) pro-inflammatory (e.g. whole wheat bread, white beans, oats, soy, eggplant, raspberries, pumpkin seeds, popcorn, etc). Occasional "cheat" foods are built into the placebo diet but with more pro-inflammatory options (e.g. two glasses of wine per week).

Placebo diet and Nabilone capsules; Placebo diet and placebo capsules

Anti-inflammatory diet OTHER

Participants will also be given a list of foods that they are allowed on the anti-inflammatory diet, and a list of foods to avoid so that they can make informed substitutions to the meals and ingredients that they are given. The study participants will be given a one-week meal plan with accompanying recipes. Occasional "cheat" foods are built into the anti-inflammatory diet (e.g. two bottles of beer per week)

Anti-inflammatory diet and Nabilone capsules; Anti-inflammatory diet and placebo capsules

Nabilone Capsules DRUG

Capsules will be 0.5mg nabilone. Participants will undergo a 5-week titration period by taking 1 (0.5mg) nabilone capsule per day for a three-day period. The dose will be increased on a fixed schedule by 1 (0.5mg) capsule every three days to a maximum of 8 capsules/day (4mg). Dosage will be maintained if higher doses are not tolerated or if sufficient relief is obtained (at least a 2-point change on the NRS). Once the appropriate nabilone (or placebo) dosage for each participant is determined, participants will begin their respective interventions over the course of the 4-week treatment period.

Anti-inflammatory diet and Nabilone capsules; Placebo diet and Nabilone capsules

Placebo capsules OTHER

Placebo capsules contain no active ingredient. Participants on placebo capsules will undergo the same 5-week titration period and intervention period as those on active treatment.

Anti-inflammatory diet and placebo capsules; Placebo diet and placebo capsules

Eligibility Criteria

• Age: 25 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 25 and over, based on year of birth
• Signed informed consent obtained prior to any study-related activities
• BMI 18-40
• A spinal cord injury at least 12 months duration, nonprogressive for at least 6 months
• At- and/or below-level neuropathic pain \>3/10 in severity on the numeric rating scale (NRS) (below-level neuropathic pain will be defined as pain \>1 dermatomal level below the neurologic level of injury). Participants will need an average \>3/10 pain over the past 7 days on screening, and to complete a daily diary for the week prior to randomization in the morning with an average pain severity of \>3/10 on at least 4 diary entries.
• Ongoing constant pain for at least 3 months, or relapsing/remitting pain for at least 6 months.
• Dosing of other pain medications (NSAIDs, opioids, non-opioid analgesics, anti-epileptic drugs, antidepressants) should be stable for at least 1 month prior to study entry.
• Females of childbearing potential must agree to use a medically approved method of birth control (e.g. hormonal contraceptives, intrauterine devices, vasectomy/tubal ligation, barrier methods and double-barrier method) and must have a negative pregnancy test results at screening and baseline.

You may not qualify if:

• History of psychotic disorder
• History of convulsive disorders
• History of substance abuse
• experienced myocardial infarction or clinically significant cardiac dysfunction within the last 12 months
• Significantly impaired hepatic function at Visit A1 or B1 (Alanine aminotransferase \[ALT\] \>5 upper limit of normal \[ULN\] or total bilirubin \[TBL\] \>2 ULN) OR the ALT or Aspartate aminotransferase (AST) \>3 ULN and TBL \>2 ULN (or international normalized ratio \[INR\] \>1.5)
• Female patients of child bearing potential and male patients whose partner is of child bearing potential, unless willing to ensure that they or their partner use effective contraception, during the study and for three months thereafter
• Female patient who is pregnant, lactating or planning pregnancy during the course of the study and for three months thereafter
• Current suicidal ideation
• Current use of cannabinoids or cannabinoid medication
• Intolerance to cannabinoids
• Traumatic SCI superimposed on prior congenital stenosis
• Preexisting myelopathy of other causes (e.g. transverse myelitis, epidural abscess, congenital spondylotic myelopathy)
• Presence of other neurologic conditions, medical conditions or pain that could confound the assessment of neuropathic pain after SCI
• Currently enrolled in another clinical trial
• Any other significant disease or disorder which, in the opinion of the investigator, may either put the patient at risk because of participation in the study, may influence the result of the study, or affect the patient's ability to participate in the study

Sponsors & Collaborators

• Eldon Loh, MD: lead
• Ontario Neurotrauma Foundation: collaborator

Study Sites (1)

St. Joseph's Health Care London - Parkwood Institute

London, Ontario, N6C 0A7, Canada

Location

Related Publications (15)

• Loh E, Guy SD, Mehta S, Moulin DE, Bryce TN, Middleton JW, Siddall PJ, Hitzig SL, Widerstrom-Noga E, Finnerup NB, Kras-Dupuis A, Casalino A, Craven BC, Lau B, Cote I, Harvey D, O'Connell C, Orenczuk S, Parrent AG, Potter P, Short C, Teasell R, Townson A, Truchon C, Bradbury CL, Wolfe D. The CanPain SCI Clinical Practice Guidelines for Rehabilitation Management of Neuropathic Pain after Spinal Cord: introduction, methodology and recommendation overview. Spinal Cord. 2016 Aug;54 Suppl 1:S1-6. doi: 10.1038/sc.2016.88.

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MeSH Terms

Conditions

Spinal Cord Injuries; Neuralgia; Pain

Interventions

nabilone

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Trauma, Nervous System; Wounds and Injuries; Peripheral Nervous System Diseases; Neuromuscular Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Eldon Loh, MD

  London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's

  PRINCIPAL INVESTIGATOR

• David Ditor, MD

  Brock University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: No other parties will be masked for the study.
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Physician

Model Details: Eligible participants who consent to study participation will be randomized to one of four groups: 1) Nabilone and Placebo Diet, 2) Placebo Capsule and Anti-inflammatory Diet, 3) Nabilone and Anti-inflammatory Diet, and 4) Placebo Capsule and Placebo Diet. Following randomization, participants will begin a study agent titration period (nabilone or placebo) in order to determine a safe and effective nabilone dose for each participant. Once the appropriate nabilone (or placebo) dosage for each participant is determined, participants will begin their respective interventions over the course of the 4-week treatment period. All outcome measures will be at assessed baseline, after the study agent titration period, and post-testing (following the 4-week treatment period).

Study Record Dates

• First Submitted: August 1, 2019
• First Posted: August 15, 2019
• Study Start: March 1, 2023
• Primary Completion: May 1, 2024
• Study Completion: December 1, 2024
• Last Updated: July 22, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)