Gastroparesis is characterized by delayed gastric emptying in association with nausea, vomiting, fullness, early satiety, and pain that has devastating impacts on quality of life. Over 5 years, the Gastroparesis Clinical Research Consortium (GpCRC) has improved understanding of this disorder and advanced goals of patients, physicians, and the NIH for its care. Much still needs to be learned about its etiology, course, and therapy that serve as rationales to continue the consortium. This application has 3 specific aims.
The first aim i s to complete approved studies of the GpCRC including NORIG, a trial of nortriptyline vs. placebo for idiopathic gastroparesis (48 of 140 patients recruited to date), GLUMIT-DG, a study of the safety, feasibility, and potential efficacy of continuous glucose monitoring and insulin pump therapy in diabetic gastroparesis (2 of 40 recruited to date with 2 screened at Univ. of Michigan, APRON, a trial of aprepitant vs. placebo for nausea of presumed gastric origin (initiating 9/2010), and PBG, the pathological basis of gastroparesis (125 biopsies of 200 planned).
The second aim i s to maintain, expand, and refine the Gastroparesis Registry that enrolled 587 patients from 2/2007-3/2010. We will follow all patients for 4 years and some for 9 years. Informed by insight from the Registry, we propose recruiting more patients to answer new questions relating to pathogenesis, severity, complications, therapies, and outcomes of gastroparesis.
The third aim will employ a novel wireless motility capsule (WMC) to characterize the role of generalized dysmotility in producing symptoms in patients with presumed gastroparesis. This study will define abnormal gastric, small intestinal and colonic transit and contractility and relate different motor defects to distinct symptom profiles of gastroparesis to give pathogenic insight relating to factors other than gastric emptying that cause different disease manifestations. The second part of the third aim will include a placebo-controlled trial of an osmotic laxative in patients with delayed gastric emptying and colon transit to test if treating distant dysmotilities improve a range of symptoms of gastroparesis. The studies of this application will significantly advance the knowledge base of the pathogenesis, clinical features, and management of this challenging disorder.

Public Health Relevance

Gastroparesis has significant impact on affected patients. Understanding of its pathogenesis and course is incomplete and current therapies are unsatisfactory for severe symptoms. This renewal offers a detailed approach to enhancing our knowledge of features, history, and causes of symptoms, and will expand treatments of this condition in novel directions beyond usual therapies to stimulate gastric emptying.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01DK073985-07
Application #
8327160
Study Section
Special Emphasis Panel (ZDK1-GRB-8 (J2))
Program Officer
Hamilton, Frank A
Project Start
2006-04-15
Project End
2016-08-31
Budget Start
2012-09-01
Budget End
2013-08-31
Support Year
7
Fiscal Year
2012
Total Cost
$155,500
Indirect Cost
$137,982
Name
University of Michigan Ann Arbor
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
073133571
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
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Parkman, Henry P; Yates, Katherine; Hasler, William L et al. (2013) Cholecystectomy and clinical presentations of gastroparesis. Dig Dis Sci 58:1062-73
Hasler, W L; Wilson, L A; Parkman, H P et al. (2013) Factors related to abdominal pain in gastroparesis: contrast to patients with predominant nausea and vomiting. Neurogastroenterol Motil 25:427-38, e300-1
Parkman, Henry P; Van Natta, Mark L; Abell, Thomas L et al. (2013) Effect of nortriptyline on symptoms of idiopathic gastroparesis: the NORIG randomized clinical trial. JAMA 310:2640-9
Iorio, Raffaele; Lucchinetti, Claudia F; Lennon, Vanda A et al. (2013) Intractable nausea and vomiting from autoantibodies against a brain water channel. Clin Gastroenterol Hepatol 11:240-5
Grover, M; Bernard, C E; Pasricha, P J et al. (2012) Clinical-histological associations in gastroparesis: results from the Gastroparesis Clinical Research Consortium. Neurogastroenterol Motil 24:531-9, e249
Pasricha, Pankaj J; Colvin, Ryan; Yates, Katherine et al. (2011) Characteristics of patients with chronic unexplained nausea and vomiting and normal gastric emptying. Clin Gastroenterol Hepatol 9:567-76.e1-4
Parkman, Henry P; Yates, Katherine P; Hasler, William L et al. (2011) Dietary intake and nutritional deficiencies in patients with diabetic or idiopathic gastroparesis. Gastroenterology 141:486-98, 498.e1-7
Hasler, William L (2011) Gastroparesis: pathogenesis, diagnosis and management. Nat Rev Gastroenterol Hepatol 8:438-53
Parkman, Henry P; Yates, Katherine; Hasler, William L et al. (2011) Clinical features of idiopathic gastroparesis vary with sex, body mass, symptom onset, delay in gastric emptying, and gastroparesis severity. Gastroenterology 140:101-15

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