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

Phase 3

Completed

• Conditions: Spinal Cord Injuries; Neuropathic Pain
• Interventions: Drug: Placebo; Drug: brivaracetam

• Registration Number: NCT05639946
• Lead Sponsor: University of Minnesota

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-11-23
• Study First Submitted QC: 2022-12-05
• Study First Posted: 2022-12-07
• Study Start: 2023-01-01
• Primary Completion: 2024-08-12
• Study Completion: 2024-10-16
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-27
• Last Update Posted: 2025-02-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 44

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Control group	Placebo	Participants with severe neuropathic pain will receive placebo drug
Experimental group	brivaracetam	Participants with severe neuropathic pain will receive brivaracetam treatment

Primary Outcome Measures

Name	Time	Method
change in pain intensity	3 months	the International Spinal Cord Injury Pain Data Set
change in operculum brain connectivity	3 months	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.
microRNA-485 levels	3 months	use Next-Generation sequencing to assess miR-485 levels

Trial Locations

Locations (1)

University of Minnesota; 🇺🇸 Minneapolis, Minnesota, United States