Gastroparesis is a disorder commonly seen in diabetes and functional dyspepsia, defined as delayed gastric emptying of solid. Major pathophysiological factors include impaired gastric accommodation, delayed gastric emptying and visceral hypersensitivity. Currently very limited treatment options are available for gastroparesis. In this project, a novel method of spinal cord stimulation (SCS) is proposed for treating gastroparesis by modulating autonomic functions. Based on physiology of gastric motility and pathophysiologies of gastroparesis, a smart SCS treatment regimens is proposed: upon initiation of food intake, SCS is programmed to relax gastric fundus (improving accommodation); at the completion of food intake, SCS is designed to improve gastric empty; when the stomach is emptying, SCS is set to treat abdominal pain or discomfort, if any. The first series of experiments are designed to optimize SCS by maximizing its effects on gastric motility in an animal model of gastroparesis; different stimulation parameters, durations and locations will be tested and compared systematically. The second and third sets of experiments are to be performed to optimize stimulation parameters to improve gastric accommodation and visceral pain, respectively. Once three best parameters sets are derived for treating three major pathophysiologies of gastroparesis, the proposed smart SCS treatment regimens will be tested and validated in canine with gastroparesis. Finally, a chronic study will be performed using an FDA approved implantable SCS system to investigate the long-term safety and efficacy of the proposed SCS method in a canine model of gastroparesis. A comprehensive and competitive team has been assembled with expertise in neuromodulation, gastroparesis and gastrointestinal motility. One of major medical device companies has been approached for collaborations; they have expressed great interests and provided enthusiastic support. The completion of this project will lead to a novel therapy for gastroparesis and the application may be extended to other functional gastrointestinal diseases such as functional dyspepsia and irritable bowel syndrome that affects more than 20% of general population.

Public Health Relevance

Gastroparesis is commonly seen in patients with diabetes and functional dyspepsia and there is lack of effective therapies. In this project we propose to treat gastroparesis using spinal cord stimulation (weak electrical current is delivered directly to the spinal cord), a minimally invasive procedure that is commonly used in treating pain.

National Institute of Health (NIH)
National Center for Advancing Translational Sciences (NCATS)
Research Demonstration--Cooperative Agreements (U18)
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Special Emphasis Panel (ZRG1)
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Tagle, Danilo A
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Johns Hopkins University
Internal Medicine/Medicine
Schools of Medicine
United States
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