U of L Clinical Center to Investigate the Pathogenesis, Etiology, and Treatment of Gastroparesis through the NIDDK Gastroparesis Consortium

Gastroparesis is a disorder of gastric function characterized by delay in gastric emptying, frequently associated
with chronic nausea and vomiting, early satiety, postprandial fullness, abdominal pain, and malnutrition that
may require nutritional support. Gastroparesis has a devastating impact on quality of life and predominantly
affects younger women. In the past 5 years, the Gastroparesis Clinical Research Consortium (GpCRC) has
made a series of important contributions (see below) to improve our understanding of this disorder and
advancing the goals of patients, physicians and the NIH for management of gastroparesis. Yet, much remains
to be learned about its etiology, natural history, treatment strategies, and clinical course, which
is the rationale behind our response to the Continuation of the Gastroparesis Consortium. The biggest barrier
to effective therapeutic approaches to gastroparesis is our lack of knowledge about either its pathogenesis or
its pathophysiology. Further, the correlation between the major symptoms such as nausea, vomiting, pain, and
current methods to measure change in gastric function (electrical, motor activity, meal emptying times) is poor
at best. Finally, we do not understand the long-term outcomes of these patients and whether outcomes differ
on the basis of etiology, symptom severity, and degree of emptying abnormalities. Consequently, our approach
to these patients is erratic and treatment has been empirical and only partially effective, if at all, in relieving the
major symptoms. The mission of the GpCRC is completely aligned with the recommendations of the National
Commission on Digestive Diseases: specifically, Research Goal 2.6 relates to gastroparesis and states:
"Understand the noxious visceral signaling causing nausea and vomiting related to gastric neuro-electrical
and/or motor dysfunction and the bi-directional brain-gut interactions. Gastroparesis provides an archetypal
disease for investigative inquiry. Chronic vomiting, a debilitating and socially isolating digestive symptom,
creates potentially life-threatening disruptions in fluid and electrolyte homeostasis and compromises nutritional
status. Chronic nausea remains a significant hidden disability. Nausea and vomiting usually occur in tandem
and overlay with other Gl symptoms as well as presenting in numerous digestive diseases. More effective
treatments for nausea and vomiting would improve quality of life and physical functioning in a vast array of
illnesses. A paucity of research exists for defining peripheral noxious signaling of nausea and vomiting related
to primary Gl motor/sensory disturbances." The Specific Aims of this proposal are to: 1. Complete the current
GpCRC registry (Registry Three); 2. Extend the GpCRC core lab, responsible for anatomic and related studies
on tissue samples of patients with Gp syndromes; 3. Perform pharmacologic studies on patients with Gp
syndromes.; 4. Perform a new device/pyloric intervention study protocol for patients with the Gp syndromes;
and 5. Utilize several novel approaches to some of the unmet needs in patients with gastroparesis symptoms,
which could be incorporated in new studies of the Consortium.

Grant Number: 5U01DK074007-19
NIH Institute/Center: NIH
Principal Investigator: Thomas Abell