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

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.

Inclusion Criteria:18 years of age or olderInjured for > 3 monthsCompleted inpatient rehabilitation and living in the communityChronic sublesional neuropathic pain defined as persistent pain (VAS grade 3-10) for three months or moreFor 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 syringomyeliaActive 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 consentPregnancy or lactationEpilepsy or active treatment for seizure disorderPast or current suicidalityActive treatment for psychiatric diseaseDrug addictionModerate 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 CImpaired renal function (GFR<60ml/minute)Contraindications to brivaracetam or pyrrolidine derivatives including allergyActive 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 brivaracetamUse of any investigational drug 30 days prior to enrollment in this studyEnrollment in another clinical trial.