OT2OD028203 (Project)

Description:The objective of the present proposal is to use the Fecobionics device developed within the SPARC OT2 program to obtain better understanding of the neurophysiological mechanism involved in sacral neuromodulation for treatment of severe fecal incontinence. The mechanism related to efficacy of sacral nerve stimulation (SNS) is not well understood. An integrated anorectal study evaluating pressure waveforms (rectal force, anal sphincter relaxation), orientation (anorectal angle and puborectalis relaxation) and bag geometry (rectal sensation, anal dimensions, and expulsion velocity) during evacuation of the novel Fecobionics device would provide tremendous insight into the mechanism of SNS. A clinical study is needed at this stage, due to the new possibilities with Fecobionics, to understand and advance neuromodulatory technologies in the field. Accordingly, the Specific aims are 1) To determine the evacuatory efficacy of nerve stimulation in a group of patients with FI with successful treatment with the Medtronic Interstim SNS. Milestone: To evaluate the immediate neuromodulatory effect of on/off stimulation on components (anal sphincter, rectal sensitivity, puborectalis) in the defecatory system; 2) To elucidate the effect of altered stimulation parameters to obtain knowledge of influence on various components in the defecatory system in a group of patients with implanted Interstim stimulator. Milestone: To compare stimulation parameters on the neuromodulatory effect on abovementioned components in the defecatory system; and 3) To apply a mathematical modeling tool to the data obtained in Aims 1-2 to provide deeper understanding of mechanical stresses in the defecatory system. Milestone: To use mathematical simulation of anorectal behavior to predict patterns and neuromodulatory mechanisms of sensory-motor action in SNS responders. Our proposal seeks to shift current research in sacral neuromodulation by using an advanced electronic simulated stool for examining the physiologic changes, multidimensionally (e.g., pressure, deformability, biomechanics, vectoral and topographic changes). The impact of our project is to test Fecobionics capabilities to provide new understanding of SNS mechanisms of action and thereby facilitate improvements in SNS therapies. This can improve predictive and therapeutic modalities and reduce healthcare costs associated with treatment of anorectal disorders that are growing epidemic with the aging population. We expect to gain new knowledge and data on the efficacy of SNS neuromodulation. The proposed studies will provide the basis for designing a prospective multi-center follow-up study where a larger patient group will be studied before and after SNS implantation for further characterizing and prediction of non-responders. Our industrial partner Medtronic has expressed great interest in the proposed studies and for supporting follow-up studies falling within the SPARC concept. The impact of the study is a better understanding of dose-response relationships between neural input and anorectal function and insight in therapeutic mechanisms. This may help optimization of existing approaches and lead to new treatment modalities.

Abbreviation:SPARC_OT2OD028203