Improving Hand Recovery with Neuromodulation in Tetraplegia (IGNITE trial)

Every year, there are approximately 18,000 new cases of spinal cord injury (SCI) in the United States, and between 250,000 and 500,000 new cases worldwide. Less than 1% of SCI survivors completely recover. Therefore, it is paramount to establish effective therapeutic interventions for chronic stages of SCI. Almost two-thirds of these cases are at the cervical level. In general, the loss of upper extremity (UE) function that accompanies cervical SCI dramatically affects meaningful, independent engagement in multiple life domains. Neuroplasticity-based interventions targeting motor cortex can be beneficial in participants with incomplete SCI, because the partially preserved cord remains interconnected with the brain by spared fibers. Several lines of evidence indicate that a non-invasive form of brain stimulation called transcranial direct current stimulation (tDCS) can facilitate motor recovery after neurological disorders. Through the application of tDCS paired with motor training, we aim to facilitate corticospinal neuroplastic change that maximizes efficient use of the spared spinal cord after SCI. In our feasibility study, we show that tDCS paired with UE motor training can improve function in chronic incomplete cervical SCI. This proposal is aimed to expand on the findings of our feasibility data including additional SCI-specific functional outcomes and qualitative outcomes to better understand the impact of our intervention outside the laboratory setting as well as longer follow-up evaluations. The central hypothesis is that participants with chronic cervical incomplete SCI receiving active tDCS paired with motor training will have greater improvement in UE motor function and quality of life compared with controls receiving sham tDCS paired with identical motor training. Furthermore, we expect that the magnitude of the behaviorally-measured effect will correlate with indices of neuroplastic changes measured by transcranial magnetic stimulation (TMS). Finally, following the recent agenda developed by an international multidisciplinary community for SCI research, and to maximize the value of our data, we are proposing a mixed-methods study, collecting both quantitative and qualitative outcomes. To this end, we propose a double-blind, randomized sham controlled mixed-method study and plan to enroll 36 participants with a chronic, incomplete cervical SCI at neurological level C4-C8 classified as B, C or D by the American Spinal Injury Association Impairment Scale. There will be 24 intervention sessions with evaluations conducted at baseline, post-intervention, and after 1 month and 4 months. Our proposal stands as singularly innovative in that we will evaluate adjuvant effects between tDCS and intensive motor training in incomplete SCI inside and outside the laboratory setting. We have tailored our training to optimize functional UE recovery1-3 and have designed our methodology to unveil indices of related neuroplasticity measured by TMS. Our use of mixed methods will allow us to establish how meaningful our proposed intervention is in the lives of our participants. As a result, novel discovery will emerge regarding how to optimize interventions targeting functional outcomes.