Our targeted medical condition is detrusor underactivity, a bladder problem in which individuals are unable to effectively empty their bladder. This is a widespread clinical problem that receives far less attention than overactive bladder and incontinence conditions. We propose to use neuromodulation of the pudendal nerve, with the Medtronic Interstim implantable neurostimulator, to evaluate stimulation-driven voiding in patients that are receiving the stimulator as a treatment for bladder problems. We expect that this study represents a low level of risk. Although we are studying an implant, the Interstim device is approved by the FDA for the conditions under study and we are already implanting the device at this location, in an off-label use. We will use imaging and electrophysiology to map the pudendal nerve in ten patients receiving the implant. Next, we will create patient-specific computational models of the implant and nerve, allowing us to simulate optimal stimulation paradigms for recruiting bladder excitation pathways in the pudendal nerve. These optimal paradigms will be evaluated in a follow-up test session with patients in which we will seek to drive bladder voiding responses. The final two participants in this study will have detrusor underactivity, allowing us to evaluate whether our approach works in the target patient group. Our study outcomes will include demonstrating successfully-driven bladder contractions and voiding, creating validated patient-specific computational models of pudendal nerve stimulation, and mapping pudendal nerve anatomy. Figure 1 shows our overall study design, with example figures of our anticipated study progression as implemented for another neuromodulation approach by our team [1]. A primary objective of the SPARC program is to enhance knowledge of anatomical and functional neural innervation of autonomic organs towards improved neuromodulation therapies. We believe our project aligns perfectly with this objective, as we will use imaging and electrophysiology techniques to map a key nerve innervating pelvic organs in a relevant clinical population. A principal outcome of the entire SPARC program will be a model for simulating a user-selected neuromodulation therapy on an end organ. Our plan to perform patient-specific modeling of pudendal nerve neuromodulation directly aligns with this program outcome, and may integrate directly within that simulator.
