Intragastric Mechanical Systems for Dysmotility Diagnosis and Obesity Treatment

Abstract

Obesity represents one of the critical non-communicable global epidemics of our time affecting over 40% of the U.S. population and its impact continuously expands. The gastrointestinal (GI) tract is the main site of food digestion, nutrient absorption, and recognized to have a significant role in the signaling of satiety. This thesis aims to address two major healthcare challenges stemming from the obesity epidemic, dysmotility evaluation and intervention to simulate satiety as a mode of therapy. Specifically, dysmotility, often associated with metabolic derangements including diabetes mellitus and obesity, can be challenging to evaluate with precision. Satiety induction also remains a major challenge due to functional requirements including minimal invasiveness and long-term efficacy. This thesis presents the fundamental mechanics, materials development and electronic underpinnings of novel interventions that address both diagnostic and therapeutic unmet needs.

Clinical evaluation of GI motility is currently limited to radiographic and nuclear methods that provide information on gastric emptying rate. While high-resolution manometry is used to evaluate motility in narrow tubular organs, such as the esophagus and rectum, there is no analogous system for gastric motility evaluation. To address this, I have developed a motility mapping platform capable of 3D pressure distribution mapping within the stomach. This incorporates the development of new materials for sensors which can operate within the dynamic range of forces experienced in the GI tract, the mechanical framework to support engagement with gastric wall and the electronics to support sensing and recording of the contractile forces. The platform has also been validated in the esophagus and rectum and compared to Food and Drug Administration (FDA)-approved high-resolution manometry devices. This new motility mapping system could revolutionize the understanding, diagnosis, and treatment of poorly understood conditions such as functional dyspepsia by enabling three-dimensional in vivo characterization of motility in the stomach.

Current intragastric balloon therapy may be limited by a lack of persistent weight loss, as static balloons have been associated with plateauing of weight loss in large mammals. We hypothesized that the plateauing 3 is associated with gastric accommodation of the static balloon and loss of stimuli. To address this challenge, I developed a novel endoscopically administered gastric resident device that supports dynamic satiety induction to approximate the natural satiety induction process associated with episodic meal ingestion. The device expands before meals to occupy the gastric cavity, then shrinks to a minimal volume after the meal. I have developed two gastric residency and dynamic expansion mechanisms based on motorized and balloon approaches. I conducted preliminary evaluation of the system in vitro and in vivo using the swine model. This minimally invasive system enables dynamic satiety induction to support weight loss.