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 RFA-DK-10-502. 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;5 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; 2. To continue the GpCRC core lab, responsible for anatomic and related studies on tissue sample of patients with Gp syndromes; 3. Continue pharmacologic studies on patients with Gp syndromes; 4. Continue device studies for patients with the Gp syndromes; and 5. A new multicenter study, based on several GpCRC ancillary studies and other pilot data.

Public Health Relevance

This proposal aims to gather a better understanding of gastroparesis which is a devastating disorder in predominantaly younger women. This is a continuation of the Gastroparesis Clinical Research Consortium (GpCRC). The GpCRC has made a series of important contributions to improve our understanding of this disorder and advancing the goals of patients, physicians and the NIH for management of gastroparesis. This proposal continues the mission of the GpCRC to better understand and treat this disorder.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01DK074007-12
Application #
9357568
Study Section
Special Emphasis Panel (ZDK1)
Program Officer
Hamilton, Frank A
Project Start
2006-04-15
Project End
2021-08-31
Budget Start
2017-09-01
Budget End
2018-08-31
Support Year
12
Fiscal Year
2017
Total Cost
Indirect Cost
Name
University of Louisville
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
057588857
City
Louisville
State
KY
Country
United States
Zip Code
40208
Parkman, H P; Hallinan, E K; Hasler, W L et al. (2017) Early satiety and postprandial fullness in gastroparesis correlate with gastroparesis severity, gastric emptying, and water load testing. Neurogastroenterol Motil 29:
Grover, M; Bernard, C E; Pasricha, P J et al. (2017) Diabetic and idiopathic gastroparesis is associated with loss of CD206-positive macrophages in the gastric antrum. Neurogastroenterol Motil 29:
Koch, K L; Hasler, W L; Yates, K P et al. (2016) Baseline features and differences in 48 week clinical outcomes in patients with gastroparesis and type 1 vs type 2 diabetes. Neurogastroenterol Motil 28:1001-15
Agrawal, Anubhav; Francis, Sean Lamar; Deveneau, Nicolette Elizabeth et al. (2016) Gastric Electrical Stimulation and Sacral Electrical Stimulation: A Long-Term Follow-Up Study of Dual-Device Treatment. Dig Dis Sci 61:176-80
Parkman, H P; Hallinan, E K; Hasler, W L et al. (2016) Nausea and vomiting in gastroparesis: similarities and differences in idiopathic and diabetic gastroparesis. Neurogastroenterol Motil 28:1902-1914
Smith, Alison; Cacchione, Robert; Miller, Ed et al. (2016) Mini-laparotomy with Adjunctive Care versus Laparoscopy for Placement of Gastric Electrical Stimulation. Am Surg 82:337-42
Hughes, Joy D; Nayak, Neeta G; Aslam, Naeem et al. (2015) Autonomic and Enteric Nervous System Dysfunction May Play a Role in Hyperemesis Gravidarum. Gastroenterology Res 8:153-156
Aslam, Naeem; Kedar, Archana; Nagarajarao, Harsha S et al. (2015) Serum catecholamines and dysautonomia in diabetic gastroparesis and liver cirrhosis. Am J Med Sci 350:81-6
Angeli, Timothy R; Cheng, Leo K; Du, Peng et al. (2015) Loss of Interstitial Cells of Cajal and Patterns of Gastric Dysrhythmia in Patients With Chronic Unexplained Nausea and Vomiting. Gastroenterology 149:56-66.e5
Pasricha, Pankaj J; Yates, Katherine P; Nguyen, Linda et al. (2015) Outcomes and Factors Associated With Reduced Symptoms in Patients With Gastroparesis. Gastroenterology 149:1762-1774.e4

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