Brivaracetam to Reduce Neuropathic Pain in Chronic SCI: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

Study Overview
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Brief Summary
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Spinal cord injury (SCI) is associated with severe neuropathic pain that is often refractory to pharmacological intervention. Preliminary data suggest brivaracetam is a mechanism-based pharmacological intervention for neuropathic pain in SCI. Based on this and other reports in the literature, SCI-related neuropathic pain is hypothesized to occur largely because of upregulation of synaptic vesicle protein 2A (SV2A) within the substantia gelatinosa of the injured spinal cord. Furthermore, compared to placebo, brivaracetam treatment is hypothesized to reduce severe below-level SCI neuropathic pain and increases parietal operculum (partsOP1/OP4) connectivity strength measured by resting-state functional Magnetic Resonance Imaging (rsfMRI). Circulating miRNA-485 levels may be associated with change in pain intensity due to brivaracetam treatment. The study aims to determine the efficacy of brivaracetam treatment for SCI-related neuropathic pain.

Official Title
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Brivaracetam to Reduce Neuropathic Pain in Chronic SCI: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

Conditions
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Spinal Cord Injuries, Neuropathic Pain

Intervention / Treatment
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* Drug: brivaracetam
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years of age or older Injured for &gt; 3 months Completed inpatient rehabilitation and living in the community Chronic sublesional neuropathic pain defined as persistent pain (VAS grade 3-10) for three months or more For people of child-bearing potential: currently practicing an effective form of two types of birth control (defined as those, alone or in combination, that result in a low failure rate (i.e., less than 1% per year) when used consistently and correctly). Exclusion Criteria: Progressive myelopathy secondary to posttraumatic cord tethering or syringomyelia Active use of drugs known to interact with brivaracetam: rifampin, carbamazepine, sodium oxybate, buprenorphine, propoxyphene, levetiracetam, and phenytoin. Brain injury or cognitive impairment limiting the ability to follow directions or provide informed consent Pregnancy or lactation Epilepsy or active treatment for seizure disorder Past or current suicidality Active treatment for psychiatric disease Drug addiction Moderate or heavy alcohol intake (up to four alcoholic drinks for men and three for women in any single day, and a maximum of 14 drinks for men and 7 drinks for women per week) Hepatic cirrhosis, Child-Pugh grades A, B, and C Impaired renal function (GFR&lt;60ml/minute) Contraindications to brivaracetam or pyrrolidine derivatives including allergy Active clinically significant disease (e.g., renal, hepatic, neurological, cardiovascular, pulmonary, endocrine, psychiatric, hematologic, urologic, or other acute or chronic illness) that, in the opinion of the investigator, would make the patient an unsuitable candidate for this trial. History of malabsorption or other gastrointestinal (GI) disease that may significantly alter the absorption of brivaracetam Use of any investigational drug 30 days prior to enrollment in this study Enrollment in another clinical trial.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental group<br>Participants with severe neuropathic pain will receive brivaracetam treatment | Drug: brivaracetam<br>* Drug dosage will be individually titrated for each participant with a goal of 100mg BID according to the following dose escalation protocol that we use clinically: 50mg BID for 2 weeks, followed by 50mg TID for 2 weeks, followed by 100mg BID for 48 days as tolerated. Participants will be allowed to reduce the dose of brivaracetam if they experience unacceptable side effects defined as increased somnolence according to routine clinical practice with other drugs in this class used for pain.<br>|
| Placebo Comparator: Control group<br>Participants with severe neuropathic pain will receive placebo drug | Drug: Placebo<br>* Participants will receive placebo drug<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change in pain intensity | the International Spinal Cord Injury Pain Data Set | 3 months | 
| change in operculum brain connectivity | assess changes in cortical activity of related pain perception regions and networks in the brain in response to brivaracetam treatment compared to placebo using rsfMRI and pain- related task-based fMRI. | 3 months | 
| microRNA-485 levels | use Next-Generation sequencing to assess miR-485 levels | baseline | 
| microRNA-485 levels | use Next-Generation sequencing to assess miR-485 levels | 3 months |