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

NCT05639946 | Completed Phase 3 Results FDA Drug

• 1 other identifier: PMR-2022-30886
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

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.

Conditions

Spinal Cord Injuries; Neuropathic Pain

Outcome Measures

Primary Outcomes (10)

• The International Spinal Cord Injury Pain Data Set (ISCIPBDS) (Version 2.0) - Change in Average Worst Neuropathic Pain Intensity

  The International Spinal Cord Injury Pain Data Set (ISCIPBDS) (Version 2.0) - Average Worst Neuropathic Pain Intensity assesses the average worst neuropathic pain intensity in the last week using a 0-10 numerical rating scale where higher scores represent greater pain intensity. Change in pain intensity will be evaluated by comparing baseline intensity with 7-week post intervention intensity.

  7 Weeks Post Intervention

• The International Spinal Cord Injury Pain Data Set (ISCIPBDS) (Version 2.0) - Change in Composite Neuropathic Pain

  The International Spinal Cord Injury Pain Data Set (ISCIPBDS) (Version 2.0) - Change in Composite Neuropathic Pain assesses the average of the three worst neuropathic pain intensities in the last week using a 0-10 numerical rating scale where higher scores represent greater pain intensity. Change in average pain intensity will be evaluated by comparing baseline average intensity with 7-week post intervention average intensity.

  7 Weeks Post Intervention

• The International Spinal Cord Injury Pain Data Set (ISCIPBDS) (Version 2.0) - Change in Pain Intensity Averaged Over All Pain Sites

  The International Spinal Cord Injury Pain Data Set (ISCIPBDS) (Version 2.0) - Change in Pain Intensity Averaged over all Pain Sites assesses the average pain intensities over all pain sites in the last week using a 0-10 numerical rating scale where higher scores represent greater pain intensity. Change in average pain intensity for all pain sites will be evaluated by comparing baseline average intensity with 7-week post intervention average intensity over all pain sites.

  7 Weeks Post Intervention

• The International Spinal Cord Injury Pain Data Set (ISCIPBDS) (Version 2.0) - Change in Pain Day-to-Day Pain Interference

  The International Spinal Cord Injury Pain Data Set (ISCIPBDS) (Version 2.0) - Change in Pain Day-to-Day Pain Interference assesses interference of the worst neuropathic pain with daily activities in the last week using a 0-10 numerical rating scale where higher scores represent greater pain interference. Change in pain interference on daily activities will be evaluated by comparing baseline interference with 7-week post intervention interference.

  7 Weeks Post Intervention

• The International Spinal Cord Injury Pain Data Set (ISCIPBDS) (Version 2.0) - Change in Pain Interference With Mood

  The International Spinal Cord Injury Pain Data Set (ISCIPBDS) (Version 2.0) - Change in Pain Interference with Mood assesses the interference of the worst neuropathic pain on mood in the last week using a 0-10 numerical rating scale where higher scores represent greater pain interference. Change in pain interference on mood will be evaluated by comparing baseline interference with 7-week post intervention interference.

  7 Weeks Post Intervention

• The International Spinal Cord Injury Pain Data Set (ISCIPBDS) (Version 2.0) - Change in Pain Interference With Sleep

  The International Spinal Cord Injury Pain Data Set (ISCIPBDS) (Version 2.0) - Change in Pain Interference with Sleep assesses the interference of the worst neuropathic pain on sleep in the last week using a 0-10 numerical rating scale where higher scores represent greater pain interference. Change in pain interference on sleep will be evaluated by comparing baseline interference with 7-week post intervention interference.

  7 Weeks Post Intervention

• The International Spinal Cord Injury Pain Data Set (ISCIPBDS) (Version 2.0) - Change in Composite Pain Interference

  The International Spinal Cord Injury Pain Data Set (ISCIPBDS) (Version 2.0) - Change in Composite Pain Interference assesses the average overall interference of the worst neuropathic pain (average interference of daily activities, mood, and sleep) in the last week using a 0-10 numerical rating scale where higher scores represent greater pain interference. Change in overall interference will be evaluated by comparing baseline overall interference with 7-week post intervention overall interference.

  7 Weeks Post Intervention

• 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. Although MRI data were acquired, the predefined functional connectivity analysis pipeline was not completed; therefore, no operculum connectivity outcomes were generated or analyzed for this study.

  7 weeks

• 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

  7 weeks

Study Arms (2)

Experimental group

EXPERIMENTAL

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 1 week followed by 100mg BID for 28 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. Drug discontinuation at study completion will be done according to the following protocol we use clinically that will be initiated for 2 weeks: reduction to 50mg BID for 1 week followed by 50mg daily for 1 week.

Drug: brivaracetam

Control group

PLACEBO COMPARATOR

Participants with severe neuropathic pain will receive placebo drug

Drug: Placebo

Interventions

brivaracetam DRUG

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 1 week followed by 100mg BID for 28 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. Drug discontinuation at study completion will be done according to the following protocol we use clinically that will be initiated for 2 weeks: reduction to 50mg BID for 1 week followed by 50mg daily for 1 week.

Experimental group

Placebo DRUG

Participants will receive placebo drug

Control group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Minnesota: lead

Study Sites (1)

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

MeSH Terms

Conditions

Spinal Cord Injuries; Neuralgia

Interventions

brivaracetam

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Trauma, Nervous System; Wounds and Injuries; Peripheral Nervous System Diseases; Neuromuscular Diseases; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

The clinical trial allowed for in-person or fully remote participation; and when participating fully remote, in-person data collection were allowed not to be collected (e.g. MRI scan, blood banking for microRNA). Therefore, the clinical trial did not have sufficient paired data collected to analyze MRI or microRNA outcomes.

Results Point of Contact

• Title: Angela Philippus
• Organization: University of Minnesota

phili272@umn.edu

(612) 626-5399

Study Officials

• Ricardo Battaglino, PhD

  University of Minnesota

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 23, 2022
• First Posted: December 7, 2022
• Study Start: January 1, 2023
• Primary Completion: October 7, 2024
• Study Completion: October 16, 2024
• Last Updated: March 18, 2026
• Results First Posted: March 18, 2026

Record last verified: 2026-02

Locations

US (1)