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

University of Minnesota (UMN)

Status and phase: Completed; Phase 3

Conditions: Spinal Cord Injuries; Neuropathic Pain

Treatments: Drug: Placebo; Drug: brivaracetam

Study type: Interventional

Funder types: Other

Identifiers

NCT05639946

PMR-2022-30886

Details and patient eligibility

About

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.

Enrollment: 44 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 18 years of age or older
• Injured for > 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<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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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44 participants in 2 patient groups, including a placebo group

Experimental group

Experimental group

Description:

Participants with severe neuropathic pain will receive brivaracetam treatment

Treatment:

Drug: brivaracetam

Control group

Placebo Comparator group

Description:

Participants with severe neuropathic pain will receive placebo drug

Treatment:

Drug: Placebo