While the pilot clinical trial had encouraging results, it did not confirm exactly how the stimulation is working. The team hypothesizes the stimulation specifically reduces signaling in what is called the spinal interceptive pathways.  

“Interoception has to do with our ability to sense the information that is coming from the body, and in this case, we are trying to evaluate whether we can modulate these specific fibers we call A Delta and C fibers,” Romo-Nava said. “We want to see how this is being achieved.” 

In the first phase of the study, the team will test their hypothesis by using an innovative method in which a brief pulse of a laser stimulus on a participant’s foot penetrates a superficial layer of skin where A Delta and C fibers are located. 

The signal produced by the laser travels from the foot to the spinal cord and eventually to the brain, where its particular signal, called a laser-evoked potential, can be captured using an electroencephalogram (EEG) cap. 

“If the stimulation is inhibiting signaling on that pathway, we would expect to see a change in the laser-evoked potential form, either by it taking longer to be generated or by a decrease in its amplitude,” Romo-Nava said. “If we’re able to see that change, then we would be successfully showing that we are indeed able to modulate these very specific fibers at this very specific anatomical location in the spinal cord because we know how this signal is generated and where in the brain it’s generated.” 

Researchers will also test different dose levels of the stimulation in this phase to see if an increased amperage will increase the effects of the stimulation and determine the optimal dose. Romo-Nava noted that even the highest dosage being tested is a very small current that is known to not be strong enough to cause tissue damage. 

A total of 67 participants will be enrolled in the first phase of the trial and receive three different dose levels of stimulation and one placebo stimulation over the course of five weeks. The trial’s primary outcome measure will be the effect of the stimulation on the laser-evoked potentials, but the team will also gather data on the stimulation’s safety and tolerability. 

If the first phase does not find the stimulation has an effect on spinal interceptive pathways using pre-established criteria, the study will end there. But if it has positive results, the team will move on to the second phase of the trial, which is a more traditional double-blinded, randomized controlled trial. 

In this phase, approximately 80 participants will be enrolled and randomized to either receive the spinal cord stimulation at the optimal dose found in the first phase or a placebo stimulation over eight weeks. Researchers will continue to gather laser-evoked potential data but will also study the effect of the stimulation on depressive symptoms. 

This two-phase innovation-funding mechanism is designed to conduct early stage testing of new interventions to treat psychiatric disorders, and Romo-Nava and the team are excited to continue this line of research.

“We believe that this allows us to generate additional evidence on whether we need to continue to pursue this pathway and how we need to develop and explore these potentially new fields in the area of mental health,” he said. “It is exciting because our team is in uncharted territories, and we need to make sure that we do it right because it is important to know if this could help patients struggling with depression and other psychiatric disorders.” 

If the stimulation is found to be safe and effective at treating depressive symptoms, Romo-Nava said it could change the way researchers and clinicians understand symptoms of psychiatric disorders in addition to potentially making a meaningful impact on individual patients. 

“It would further support looking at the brain as a very complex organ that is constantly sending information out and receiving information rather than studying it as an isolated box,” he said. “This would support the notion that in order to understand psychiatric disorders, you need to incorporate additional layers of complexity.” 

For more information on enrolling in the study, please call 513-536-0707, email georgi.georgiev@lindnercenter.org or fill out a pre-screening questionnaire.

Innovation Lives Here

The multidisciplinary study team is led by Romo-Nava and co-investigators Susan L. McElroy, MD, Jeffrey Welge, PhD, and Dave Fleck, PhD, at UC’s Department of Psychiatry and Behavioral Neuroscience; Oluwole Awosika, MD, at UC’s Department of Neurology and Rehabilitation Medicine; and Ishita Basu, PhD, at UC’s Department of Neurosurgery. Martin Paulus, MD, from the Laureate Institute for Brain Research, and Jeff Liu Chang-chia, PhD, from the University of Virginia will be consultants on the study. Key team members at the Lindner Center of HOPE Research Institute are the lead research coordinators Georgi Georgiev and Christina Charnas; research nurse Nicole Mori; biostatistician Thomas J. Blom; Anna I. Guerdjikova, PhD; Jakyb Stoddard; Aspen Madrid; Genie Groff; and Phong Phan, PhD, UC/Lindner Center of HOPE postdoctoral fellow. 

Research reported in this publication was supported by the National Institute of Mental Health of the National Institutes of Health under Award Number 1R61MH133770-01A1. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.   

Featured photo at top of  Romo-Nava preparing to apply the laser pulse to a participant. All photos/Andrew Higley/UC Marketing + Brand.