Clinical trial NCT04057456: Cannabinoids and an Anti-inflammatory Diet for the Treatment of Neuropathic Pain After Spinal Cord Injury
Official title: Cannabinoids and an Anti-inflammatory Diet for the Treatment of Neuropathic Pain After Spinal Cord Injury
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Spinal Cord Injuries
Neuropathic Pain
Keywords: Nabilone
Spinal Cord Injury
Neuropathic pain
Pain
Anti Inflammatory Diet
Lead sponsor: London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
Sponsor class: OTHER
Collaborators: name: Ontario Neurotrauma Foundation
First posted: 2019-08-15
Enrollment: 140
Sex: ALL
Minimum age (years): 25
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Intervention model description: 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).
Primary purpose: TREATMENT

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.

Detailed description: Nabilone and an anti-inflammatory diet are two novel treatments that may be beneficial for managing Neuropathic Pain (NP) after Spinal Cord Injury (SCI).

Neuropathic pain is a common complication following 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. Cannabinoids and an anti-inflammatory diet may provide pain relief while being better tolerated.

The Co- Sponsor Investigators will test the potential benefits of these treatments for neuropathic pain after SCI.

Clinically, cannabinoids have been shown to be effective in the management of central NP after multiple sclerosis (MS), and although they have been trialed for a variety of complications after SCI, direct evidence for their ability to manage NP in this population is limited. Further, no studies have evaluated the efficacy of synthetic cannabinoids (nabilone) for the treatment of NP after SCI. Accordingly, the CanPainSCI Clinical Practice Guidelines concluded that the evidence is insufficient to develop a specific recommendation regarding cannabinoids in the treatment of NP after SCI. In addition, relevant side effects for those with SCI have not been well documented. Despite this, cannabinoids have been increasingly used as a treatment option for NP after SCI, particularly given increased access to, and greater societal acceptance of, cannabinoids in general. Studies that evaluate the effectiveness and side effects of cannabinoids and synthetic cannabinoids in the SCI population are therefore urgently needed.

An anti-inflammatory diet has recently shown promise in the management of NP after SCI. An RCT comparing an anti-inflammatory diet to placebo identified a reduction in sensory NP symptoms following SCI. This RCT was done in a general population of SCI patients and did not necessarily select those who were experiencing significant neuropathic pain. Therefore, additional evidence to demonstrate treatment effect will be important to justify widespread adoption of this diet for NP after SCI.

The study will collect data on a sample of up to 140 patients with SCI and at- and/or below-level neuropathic pain \>3/10 in severity on the numeric rating scale.

The Principal Investigators will assess the treatment's effects on quality of life and pain management. If the study is successful, the results (and an evaluation of the process) will be used to inform an affordable and sustainable anti-inflammatory nutrition program to be implemented at Power Cord. This nutrition program will also be widely disseminated and potentially act as a template for similar programs In SCI care centres across Canada.

This study will assess blood samples at three time points for analysis of pro and anti-inflammatory markers. The research coordinator (blinded to the randomization) will assess patients using various quality of life and pain assessment questionnaires during clinic visits, at home or by telephone interview.

The type, level, and completeness of injury will be documented, and, if necessary, updated at each in-person visit. Each participant will be provided with instructions and study schedule. Protocol compliance will be tested through product count and interviews at each follow-up visit. Side effects will be assessed using standardized case report forms at each visit. Study visits may be in person or over the phone. Participants will be encouraged to report any events they may experience directly to the coordinator.

Participants who withdraw consent to continue treatments, will be encouraged to undergo the planned assessments. Withdrawal at the request of investigators or medical personnel may include, but are not limited to:

1. Symptoms are deemed to be potentially related to the study product
2. New diagnosis of exclusion criteria;
3. Unacceptable side effects;
4. Death

Estimated time to complete recruitment: Averaging 36 months, approximately 3 years.

Eligibility criteria: Inclusion:

1. Age 25 and over, based on year of birth
2. Signed informed consent obtained prior to any study-related activities
3. BMI 18-40
4. A spinal cord injury at least 12 months duration, nonprogressive for at least 6 months
5. 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.
6. Ongoing constant pain for at least 3 months, or relapsing/remitting pain for at least 6 months.
7. 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.
8. Any cannabinoids, or cannabinoid medications (e.g. nabilone) will need to be stopped at least 1 month prior to screening for and inclusion in the study.
9. 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.

Exclusion:

1. History of psychotic disorder
2. History of convulsive disorders
3. History of substance abuse
4. experienced myocardial infarction or clinically significant cardiac dysfunction within the last 12 months
5. 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)
6. 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
7. Female patient who is pregnant, lactating or planning pregnancy during the course of the study and for three months thereafter
8. Current suicidal ideation
9. Current use of cannabinoids or cannabinoid medication
10. Intolerance to cannabinoids
11. Traumatic SCI superimposed on prior congenital stenosis
12. Preexisting myelopathy of other causes (e.g. transverse myelitis, epidural abscess, congenital spondylotic myelopathy)
13. Presence of other neurologic conditions, medical conditions or pain that could confound the assessment of neuropathic pain after SCI
14. Currently enrolled in another clinical trial
15. 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
16. Following a physical examination, the patient has any abnormalities that, in the opinion of the investigator would prevent the patient from safe participation in the study

Primary outcomes:
measure: Average pain intensity
timeFrame: Baseline and 9 weeks
measure: Sensory changes
timeFrame: Baseline and 9 weeks
measure: Pain relief
timeFrame: Baseline and 9 weeks
Secondary outcomes:
measure: Patient global impression of change
timeFrame: Baseline and 9 weeks
measure: Financial feasibility of following anti-inflammatory diet
timeFrame: 9 weeks
measure: Mood Centre for Epidemiologic Studies-Depression scale
timeFrame: Baseline and 9 weeks
measure: Sleep
timeFrame: Baseline and 9 weeks
measure: Spasticity
timeFrame: Baseline and 9 weeks
measure: Pro-Inflammatory biomarkers
timeFrame: Baseline and 9 weeks
measure: Profile of Mood States
timeFrame: Baseline and 9 weeks
measure: Anti-Inflammatory Biomarkers
timeFrame: Baseline and 9 weeks
Other outcomes:
Locations:
city: London
country: Canada
facility: St. Joseph's Health Care London - Parkwood Institute
state: Ontario
Study officials:
affiliation: London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
name: Eldon Loh, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Brock University
name: David Ditor, MD
role: PRINCIPAL_INVESTIGATOR
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