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

Primary Purpose

Spinal Cord Injuries, Neuropathic Pain

Status
Recruiting
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
brivaracetam
Placebo
Sponsored by
University of Minnesota
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Spinal Cord Injuries

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

  • University of MinnesotaRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Experimental group

Control group

Arm Description

Participants with severe neuropathic pain will receive brivaracetam treatment

Participants with severe neuropathic pain will receive placebo drug

Outcomes

Primary Outcome Measures

change in pain intensity
the International Spinal Cord Injury Pain Data Set
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.
microRNA-485 levels
use Next-Generation sequencing to assess miR-485 levels
microRNA-485 levels
use Next-Generation sequencing to assess miR-485 levels

Secondary Outcome Measures

Full Information

First Posted
November 23, 2022
Last Updated
February 10, 2023
Sponsor
University of Minnesota
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1. Study Identification

Unique Protocol Identification Number
NCT05639946
Brief Title
Brivaracetam to Reduce Neuropathic Pain in Chronic SCI: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial
Official Title
Brivaracetam to Reduce Neuropathic Pain in Chronic SCI: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
January 1, 2023 (Actual)
Primary Completion Date
January 1, 2028 (Anticipated)
Study Completion Date
January 1, 2028 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Minnesota

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Spinal Cord Injuries, Neuropathic Pain

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Experimental group
Arm Type
Experimental
Arm Description
Participants with severe neuropathic pain will receive brivaracetam treatment
Arm Title
Control group
Arm Type
Placebo Comparator
Arm Description
Participants with severe neuropathic pain will receive placebo drug
Intervention Type
Drug
Intervention Name(s)
brivaracetam
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Participants will receive placebo drug
Primary Outcome Measure Information:
Title
change in pain intensity
Description
the International Spinal Cord Injury Pain Data Set
Time Frame
3 months
Title
change in operculum brain connectivity
Description
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.
Time Frame
3 months
Title
microRNA-485 levels
Description
use Next-Generation sequencing to assess miR-485 levels
Time Frame
baseline
Title
microRNA-485 levels
Description
use Next-Generation sequencing to assess miR-485 levels
Time Frame
3 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Angela Philippus
Phone
612-625-2661
Email
phili272@umn.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ricardo Battaglino, PhD
Organizational Affiliation
University of Minnesota
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ricardo Battaglino,, PhD
Phone
612-625-2661
Email
rbattagl@umn.edu

12. IPD Sharing Statement

Learn more about this trial

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

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