Written by Dr. Kimberly Anderson
The Northeast Ohio Regional Spinal Cord Injury System (NORSCIS) provides a comprehensive, multidisciplinary approach to the care of individuals with spinal cord injury (SCI), is funded by the National Institute on Disability, Independent Living, Rehabilitation Research (NIDILRR), and is based at MetroHealth. Two key requirements of funding are to provide a comprehensive continuum of care for individuals with traumatic SCI and to conduct high quality research that is targeted at reducing the health burden of SCI by generating evidence-based interventions. Our major research study for this five-year cycle is to test the ‘Feasibility of Early Gabapentin as an Intervention for Neuroprotection’.
Now, many people may currently use or may have used gabapentin in the past to try to manage pain after SCI. Gabapentin is in fact one of the top recommended treatment options for neuropathic pain associated with SCI. However, it does not always work for everyone and in the people that it does work for it tends to reduce pain but does not completely eliminate pain.
Common side effects of gabapentin are dizziness and sleepiness. Often times medium to high doses are needed to impact neuropathic pain, which can lead to more bothersome side effects like swelling, weakness/fatigue, nausea, diarrhea, constipation, blurred vision, headache, or dry mouth. In some people these bothersome side effects may outweigh any benefit in their pain relief so they may work with their doctor to try other pain management options.
In this new study it is important to not think about gabapentin as how it is used for pain. Rather, can we rethink how gabapentin might be used to improve the outcome after SCI? In the last few years there has been a growing body of evidence that gabapentin might be able to promote neurologic recovery if used in the right time window and at the right dose. In laboratory animal models of SCI, we have learned that:
- A single low dose of gabapentin given 2-3 weeks after SCI can reduce spasticity behavior;
- Low doses of gabapentin started early after a cervical SCI and continued for 4 months nerve fibers in the neck and improvement in hand function; and
- Low-to-medium doses of gabapentin started early after SCI and continued for 4-5 weeks can reduce the frequency and severity of spontaneous and evoked autonomic dysreflexia, change the sprouting/growth of autonomic nerve fibers, and protect against SCI-induced suppression of the immune system.
There is also a growing body of evidence in humans that when gabapentin is given within the first-month post-injury for pain management, there is a small but persistent gain in motor function and sometimes an improvement in sensation. Those discoveries occurred accidentally when investigators reviewed a large European database of people living with SCI who were taking various medications for pain management during the first year of injury.
Overall, emerging animal and human evidence suggests that early initiation of low to medium doses of gabapentin and continued delivery for a range of 2 weeks to 4 months has a persistent, positive effect on motor and autonomic neurologic recovery. However, there has never been a clinical trial testing this observation. Therefore, the objective of our study is to conduct the first ever trial to test the feasibility of early administration of gabapentin as an intervention for neurorecovery. Why a feasibility trial? Because gabapentin is so widely used in SCI at many different doses and at many different times after injury, we have to first understand if we can control the dose, when we start it, and when we stop it without negatively impacting clinical care or pain management. Our trial is designed to answer the following questions:
- Can we enroll participants and start the study medication within 5 days of a new SCI?
- Can we randomize people to a low dose, a medium dose, or a no dose (placebo) and keep them on that dose daily for 90 days?
- Can we withhold any other use of gabapentin during that 90-day period?
- Can we manage pain appropriately using other kinds of medications?
- Using this approach, do we see any trends for improvement in movement, feeling, and other types of recovery?
The NORSCIS team has enrolled 5 participants already and will enroll a total of 42 over the next four years. We will then know how to move forward with gabapentin as a potential intervention for SCI.