DYNAMO STUDY: Assessing Dynamic Stimulation Patterns on SCS Efficacy in a Double-blinded Crossover RCT

Introduction: Spinal Cord Stimulation (SCS) is an established and effective neuromodulation therapy for treating medically refractory chronic pain. Current SCS technology (e.g., conventional tonic stimulation) delivers static stimulation, or waveforms with fixed, time-invariant pulses (TIP), which may limit therapy personalization and result in habituation. To build upon existing therapy, we propose novel, dynamic stimulation (DS) patterns, in which a therapeutically relevant waveform parameter (amplitude, pulse width, or rate) is configured to vary in time at a specific modulation rate and depth during stimulation[1]. Based on preliminary electrospinogram (ESG) recordings from porcine models during SCS, we hypothesize that DS patterns engage primary neuronal targets of SCS dynamically and may thereby produce pain relief with less habituation[2]. To test this hypothesis, we are undertaking a first-in-human, randomized, controlled, double-blinded crossover clinical study.

Methods: Preclinically, we recorded ESGs from an anesthetized porcine model to characterize the degree to which DS may dynamically activate the dorsal columns. Figures are included that document (A) a block diagram of the system and (B) the fully assembled system connected to a mock-patient load board. To assess clinical outcomes, we devised a novel randomized, controlled, double-blinded, crossover trial (NCT05968664)[3] with N= 31 that involves efficacy comparisons among TIP SCS, rate-modulated DS, and intensity modulated DS. Furthermore, a Stimulation Adjustment Protocol was developed for each therapy block to evaluate the therapeutic relevance and effects of DS parameters.

Results: Consistent with our hypothesis, pre-clinical ESGs revealed that dorsal columns respond variably to intensity modulated and rate modulated DS patterns, and intensity modulation generated the most variable activation among the stimulation modalities (TIP vs. rate vs. intensity) tested. To validate clinically, the DYNAMO RCT feasibility study will evaluate the ability of DS to improve SCS efficacy and longevity among a variety of primary and secondary outcome metrics, including but not limited to NRS pain scores, Oswestry Disability Index, Patient Global Impression of Change and other exploratory outcomes. The design of the study will be presented.

Conclusion: The study will be the first in humans to observe the effect of rate-modulated, amplitude-modulated, and pulse width-modulated DS and compare their performance to standard of care static stimulation therapy. Mechanistically, the dynamic nature of the proposed waveforms results in dynamic neuronal activation as observed in pre-clinical porcine recordings. Potential downstream effects of initial dynamic activation include reducing therapy tolerance, increasing robustness and duration of pain relief.