Project Details
Description
TRANSLUMBOSACRAL NEUROMODULATION THERAPY FOR FECAL INCONTINENCE:
RANDOMIZED TRIAL
PROJECT SUMMARY/ABSTRACT:
Fecal Incontinence (FI) affects 40 million Americans, predominantly women and elderly. It is a major
health care burden, significantly impairs quality of life and psychosocial function. FI is characterized
by multifactorial dysfunction that includes lumbosacral neuropathy, anorectal sensori-motor
dysfunction, and maladaptive pelvic floor-brain innervation. A critical barrier to progress in the
treatment of FI is the lack of randomized controlled trials, absence of mechanistically based non-
invasive therapies that modify disease, and a lack of understanding on how treatments affect
pathophysiology of FI, as highlighted by experts at a recent NIDDK workshop. Consequently, most
current remedies remain ineffective. Our long-term goal is to address the problem of lack of
effective treatments for FI by investigating treatments that modulate peripheral and central neuronal
perturbations and thereby improve sensory and visceromotor control, and to understand the
neurobiologic basis of these treatments. Our central hypothesis is that a novel, non-invasive
treatment consisting of Translumbosacral Neuromodulation Therapy (TNT), using repetitive
magnetic stimulation, will significantly improve FI in the short-term and long-term, by enhancing
neural excitability and inducing neuroplasticity, and thereby provide a multidimensional therapeutic
benefit. Our approach is based on compelling preliminary study which showed that TNT at 1 Hz
frequency, significantly improved FI, by enhancing bidirectional gut and brain signaling, anal sphincter
strength and rectal sensation compared to 5 or 15 Hz. Our objectives are to 1) investigate the
efficacy, safety and optimal dose of a new treatment, TNT, in a sham controlled, randomized dose-
dependent study in 132 FI patients; 2) determine the mechanistic basis for TNT by assessing the
efferent spino-anorectal and afferent pelvic floor-brain signaling, and anorectal sensori-motor
function; 3) identify the durability of treatment response and neuromodulatory effects of TNT, and
whether reinforcement TNT provides augmented improvement through enhanced adaptive
neuroplasticity, by performing a long-term, sham controlled randomized trial. Our expected
outcomes include the demonstration of TNT as a durable, efficacious, safe, mechanistically based,
non-invasive, and low risk treatment for FI. The impact of our project includes a novel, disease
modifying, non-invasive treatment for FI, a scientific basis for the development of this treatment, and
improved understanding of the pathophysiology of FI and the neurobiologic mechanism(s) of how
TNT modifies bidirectional gut and brain axes and anorectal function. Ultimately, the knowledge
generated by this project will provide new avenues for the development of innovative, evidence-based
therapies for FI.
Status | Not started |
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