Understanding subtypes of gastroparesis and the pathophysiology of symptoms associated with gastroparesis are required before improved treatments can be designed.
Our aims are to 1) define major subtypes of gastroparesis using physiological testing for gastric myoelectrical activity (GMA), accommodation, and autonomic nervous system function and 2) explore pathophysiological mechanisms of meal-induced symptoms in patients with gastroparesis and gastroparesis-like syndromes. Variable depletion of interstitial cells of Cajal (ICCs) creates a continuum of dysfunction of electrical and contractile activities of the stomach. Physiological tests to measure gastric emptying, gastric myoelectrical activity (GMA), and gastric accommodation reflect this continuum of ICC depletion from gastric dysrhythmias and normal gastric emptying to delays in gastric emptying. Our recent observations revealed two important subtypes of gastroparesis: 1) obstructive gastroparesis and 2) gastroparesis with postural orthostatic tachycardia syndrome (POTS). Preliminary studies show positive responses to pyloric therapies and to fludrocortisone and vitamin D in these subtypes, respectively. The important physiological differences in these subgroups of gastroparesis provide the rationale for more precise, individual treatments. Physiological testing during provocative test meals in symptomatic patients with normal gastric emptying (e.g. chronic unexplained nausea and vomiting, dysmotility-like dyspepsia, or postprandial distress syndrome) unmasks subtypes with: 1) gastric dysrhythmias or normal 3 cpm GMA and 2) normal or abnormal gastric accommodation. Our studies will utilize the database of Registry 2 of the Gastroparesis Clinical Research Consortium which contains extensive physiologic data in patients with idiopathic and diabetic gastroparesis and in patients with normal gastric emptying and new data from patients enrolled in the continuation of the Registry. This project will characterize clinically important subgroups of symptomatic patients with or without gastroparesis, increase our understanding of the underlying pathophysiology of gastroparesis-associated symptoms, and lead to more rational therapies based on physiological test results.

Public Health Relevance

The aim of the study is to define major subtypes of gastroparesis using tests of gastric myoelectrical activity, accommodation, and autonomic nervous system function. Understanding subtypes of gastroparesis and the pathophysiology of the symptoms associated with gastroparesis are required before improved treatments can be designed.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project--Cooperative Agreements (U01)
Project #
2U01DK073974-11
Application #
9235477
Study Section
Special Emphasis Panel (ZDK1-GRB-8 (O2)S)
Program Officer
Hamilton, Frank A
Project Start
2006-04-15
Project End
2021-08-31
Budget Start
2016-09-25
Budget End
2017-08-31
Support Year
11
Fiscal Year
2016
Total Cost
$387,500
Indirect Cost
$137,500
Name
Wake Forest University Health Sciences
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
937727907
City
Winston-Salem
State
NC
Country
United States
Zip Code
27157
Orthey, Perry; Yu, Daohai; Van Natta, Mark L et al. (2018) Intragastric Meal Distribution During Gastric Emptying Scintigraphy for Assessment of Fundic Accommodation: Correlation with Symptoms of Gastroparesis. J Nucl Med 59:691-697
Hasler, W L; May, K P; Wilson, L A et al. (2018) Relating gastric scintigraphy and symptoms to motility capsule transit and pressure findings in suspected gastroparesis. Neurogastroenterol Motil 30:
Pasricha, Pankaj J; Yates, Katherine P; Sarosiek, Irene et al. (2018) Aprepitant Has Mixed Effects on Nausea and Reduces Other Symptoms in Patients With Gastroparesis and Related Disorders. Gastroenterology 154:65-76.e11
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:
Gibbons, Simon J; Grover, Madhusudan; Choi, Kyoung Moo et al. (2017) Repeat polymorphisms in the Homo sapiens heme oxygenase-1 gene in diabetic and idiopathic gastroparesis. PLoS One 12:e0187772
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
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
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
Koch, Kenneth L (2014) Gastric dysrhythmias: a potential objective measure of nausea. Exp Brain Res 232:2553-61

Showing the most recent 10 out of 26 publications