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Gastroparesis: Medical and Therapeutic Advances

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Abstract

Gastroparesis is a chronic, bothersome, and often disabling neuromuscular disorder of the upper gastrointestinal tract. The most frequently reported symptoms of gastroparesis include nausea, vomiting, epigastric pain, early satiety, and unintentional weight loss. Etiologies of gastroparesis include diabetes, connective tissue disorders, prior infection, mesenteric ischemia, and post-surgical complications. The largest category of gastroparesis patients is comprised of those in whom no definitive cause can be identified (idiopathic gastroparesis). The individual and societal burden of gastroparesis is substantial. It considerably reduces patients’ quality of life accompanied by a significant negative impact to the healthcare system. The current treatments of gastroparesis are less than ideal. Dietary modification may improve symptoms in patients with mild disease. Metoclopramide is the only medication currently approved for the treatment of gastroparesis; however, it is associated with adverse effects in a sizable proportion of patients. Other medications are frequently employed to treat symptoms of nausea and vomiting, although technically all are used off-label since they are not FDA approved for the treatment of gastroparesis. These data highlight the need to identify novel, more effective treatment options for this disabling disease. This review will provide a brief synopsis on the epidemiology, etiology, and impact of gastroparesis, discussing new therapeutic advances.

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References

  1. Camilleri M, Parkman HP, Shafi MA, et al. Clinical guideline: management of gastroparesis. Am J Gastroenterol. 2013;108:18–37.

    Article  CAS  PubMed  Google Scholar 

  2. Parkman HP, Hasler WL, Fisher RS, for the American Gastroenterological Association, et al. American Gastroenterological Association medical position statement: diagnosis and treatment of gastroparesis. Gastroenterology. 2004;127:1589–1591.

    Article  PubMed  Google Scholar 

  3. Tougas G, Eaker EY, Abell TL, et al. Assessment of gastric emptying using a low fat meal: establishment of international control values. Am J Gastroenterol. 2000;95:1456–1462.

    Article  CAS  PubMed  Google Scholar 

  4. Abell TL, Camilleri M, Donohue K, et al. Consensus recommendations for gastric empting Scintigraphy: a joint report of the American Neurogastroenterology and Motility Society and the Society of Nuclear Medicine. Am J Gastroenterol. 2008;103:753–763.

    Article  PubMed  Google Scholar 

  5. Jung HK, Choung RS, Locke GR, et al. The incidence, prevalence and outcomes of patients with gastroparesis in Olmsted County, Minnesota from 1996 to 2006. Gastroenterology. 2009;136:1225–1233.

    Article  PubMed  Google Scholar 

  6. Lacy BE, Crowell MD, Mathis C, Bauer D, Heinberg LJ. Gastroparesis: quality of life and health care utilization. J Clin Gastroenterol. 2016. doi:10.1097/MCG.0000000000000728.

    PubMed  Google Scholar 

  7. Revicki DA, Rentz AM, Dubois D, et al. Gastroparesis Cardinal Symptom Index (GCSI): development and validation of a patient reported assessment of severity of gastroparesis symptoms. Quality Life Res. 2004;13:833–844.

    Article  Google Scholar 

  8. Wang YR, Fisher RS, Parkman HP. Gastroparesis-related hospitalizations in the United States: trends, characteristics, and outcomes, 1995–2004. Am J Gastroenterol. 2008;103:313–322.

    Article  PubMed  Google Scholar 

  9. Soykan I, Sivri B, Sarosiek I, et al. Demography, clinical characteristics, psychological and abuse profiles, treatment, and long-term follow-up of patients with gastroparesis. Dig Dis Sci. 1998;43:2398–2404.

    Article  CAS  PubMed  Google Scholar 

  10. Pande H, Lacy BE, Crowell MD. Inflammatory causes of gastroparesis: report of 5 cases. Dig Dis Sci. 2002;47:2664–2668.

    Article  CAS  PubMed  Google Scholar 

  11. Horowitz M, Harding PE, Maddox AF, et al. Gastric and oesophageal emptying in patients with type 2 (non-insulin dependent) diabetes mellitus. Diabetologia. 1989;32:151–159.

    Article  CAS  PubMed  Google Scholar 

  12. Enck P, Rathmann W, Spiekermann M, et al. Prevalence of gastrointestinal symptoms in diabetic patients and non-diabetic subjects. Z Gastroenterol. 1994;32:637–641.

    CAS  PubMed  Google Scholar 

  13. Maleki D, Locke GR 3rd, Camilleri M, et al. Gastrointestinal tract symptoms among persons with diabetes mellitus in the community. Arch Intern Med. 2000;160:2808–2816.

    Article  CAS  PubMed  Google Scholar 

  14. Bytzer P, Talley NJ, Leemon M, et al. Prevalence of gastrointestinal symptoms associated with diabetes mellitus: a population-based survey of 15,000 adults. Arch Intern Med. 2001;161:1989–1996.

    Article  CAS  PubMed  Google Scholar 

  15. Bharucha AE, Camilleri M, Veil E, et al. Comprehensive assessment of gastric emptying with a stable isotope breath test. Neurogastroenterol Motil. 2013; 25. doi:10.1111/nmo.12054.

  16. Kuo B, McCallum RW, Koch KL, et al. Comparison of gastric emptying of a nondigestible capsule to a radio-labeled meal in healthy and gastroparetic subjects. Aliment Pharmacol Ther. 2008;27:186–196.

    Article  CAS  PubMed  Google Scholar 

  17. Perkel MS, Moore C, Hersh T, Davidson E. Metoclopramide therapy in patient with delayed gastric emptying. Dig Dis Sci. 1979;24:9.

    Article  Google Scholar 

  18. Parkman HP, Carlson MR, Gonyer D. Metoclopramide nasal spray is effective in symptoms of gastroparesis in diabetics compared to conventional oral tablet. Neurogastroenterol Motil. 2014;26:521–528.

    Article  CAS  PubMed  Google Scholar 

  19. Parkman HP, Carlson MR, Gonyer D. Metoclopramide nasal spray reduces symptoms of gastroparesis in women, but not men, with diabetes: results of a phase 2B randomized study. Clin Gastroenterol Hepatol. 2015;13:1256–1263.

    Article  CAS  PubMed  Google Scholar 

  20. Wierup N, Bjorkqvist M, Westrom B, Pierzynowski S, Sundler F, Sjolund K. Ghrelin and motilin are cosecreted from a prominent endocrine population in the small intestine. J Clin Endocrinol Metab. 2007;92:3573–3581.

    Article  CAS  PubMed  Google Scholar 

  21. Page AJ, Slattery JA, Milte C, et al. Ghrelin selectively reduces mechanosensitivity of upper gastrointestinal vagal afferent. Am J Physiol Gastrointest Liver Physiol. 2007;292:1376–1384.

    Article  Google Scholar 

  22. Tack J, Depoortere I, Bisschops R, et al. Influence of ghrelin on interdigestive gastrointestinal motility in humans. Gut. 2006;55:327–333.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Harch IA, Koebnick C, Tasi AM, Hahn EG, Konturek PC. Ghrelin and obestatin levels in type 2 diabetic patients with and without delayed gastric emptying. Dig Dis Sci. 2009;54:2161–2166.

    Article  Google Scholar 

  24. Camilleri M, Acosta A. A ghrelin agonist fails to show benefit in patients with diabetic gastroparesis: let’s not throw the baby out with the bath water. Neurogastrienteol Motil. 2013;25:859–863.

    Article  CAS  Google Scholar 

  25. Shin A, Wo JM. Therapeutic applications of ghrelin agonists in the treatment of gastroparesis. Curr Gastroenterol Rep. 2015;17:8.

    Article  Google Scholar 

  26. Van der Ploeg L, Laken H, Sharma S, et al. Preclinical gastrointestinal prokinetic efficacy and endocrine effects of the ghrelin mimetic RM-131. Life Sci. 2014;109:20–29.

    Article  PubMed  Google Scholar 

  27. Camilleri M, Acosta A. Relamorelin: a novel gastricolokinetic synthetic ghrelin agonist. Neurogastroenterol Motil. 2015;27:324–332.

    Article  CAS  PubMed  Google Scholar 

  28. Nelson AD, Camilleri M, Acosta A, et al. Effects of gherelin receptor agonist, Relamorelin, on gastric motor functions and satiation in healthy volunteers. Neurogastroenterol Motil. 2016;28:1705–1713.

    Article  CAS  PubMed  Google Scholar 

  29. Shin A, Camilleri M, Busciglio I, et al. Randomized controlled phase IB study of ghrelin agonist, RM-131 in type 2 diabetic women with delayed gastric emptying: pharmacokinetics and pharmacodynamics. Diabetes Care. 2013;36:41–48.

    Article  CAS  PubMed  Google Scholar 

  30. Shin A, Camilleri M, Busciglio I, et al. The ghrelin agonist RM-131 accelerates gastric emptying of solids and reduces symptoms in patients with type 1 diabetes mellitus. Clin Gastroenterol Hepatol. 2013;11:1453–1459.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Lembo A, Camilleri M, McCallum R, et al. Relamorelin reduces vomiting frequency and severity and accelerates gastric emptying in adults with diabetic gastroparesis. Gastroenterology. 2016;151:87–96.

    Article  CAS  PubMed  Google Scholar 

  32. Camilleri M, McCallum R, Tack J, Spence S, Gottesdiener K, Fiedorek F. Relamorelin in patients with diabetic gastroparesis: Efficacy and safety results from a phase 2B randomized, double-blind, placebo-controlled, 12 week study. DDW. 2017; Abstract 638

  33. Hasler WL. Serotonin and the GI tract. Curr Gastroenterol Rep. 2009;11:383–391.

    Article  PubMed  Google Scholar 

  34. Ottoboni T, Gelder MS, O’Boyle E. Biochronomer technology and the development of APF530, a sustained release formulation of granisetron. J Exp Pharm. 2014;6:15–21.

    Article  CAS  Google Scholar 

  35. Boccia RV, Gordan LN, Clark G, Howell JD, Grunberg SM. Sancuso study group. Efficacy and tolerability of transdermal granisetron for the control of chemotherapy-induced nausea and vomiting associated with moderately and highly emetogenic multi-day chemotherapy. Support Care Cancer. 2011;19:1609–1617.

    Article  PubMed  Google Scholar 

  36. Kuryshev YA, Brown AM, Wang L, Benedict CR, Rampe D. Interactions of the 5-Hydroxytryptamine 3 antagonist class of antiemetic drugs with human cardiac ion channels. J Phamacol Exp Ther. 2000;295:614–620.

    CAS  Google Scholar 

  37. Manson JW, Selness DS, Moon TE, O’Mahony B, Donachie P, Howell J. Pharmacokinetics and repolarization effects of intravenous and transdermal granisetron. Clin Cancer Res. 2012;18:2913–2921.

    Article  Google Scholar 

  38. Simmons K, Parkman HP. Granisetron transdermal system improves refractory nausea and vomiting in gastroparesis. Dig Dis Sci. 2014;59:1231–1234.

    Article  PubMed  Google Scholar 

  39. Midani D, Parkman HP. Granisetron transdermal system for treatment of symptoms of gastroparesis: a prescription registry study. J Neurogastroenterol Motil. 2016;22:650–655.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Briejer MR, Akkermans LM, Schuurkes JA. Gastrointestinal prokinetic benzamides: the pharmacology underlying stimulation of motility. Pharmacol Rev. 1995;47:631–651.

    CAS  PubMed  Google Scholar 

  41. De Maeyer JH, Lefebvre RA, Schuurkes JA. 5-HT4 receptor agonists: similar but not the same. Neurogastroenterol Motil. 2008;20:99–112.

    Article  PubMed  Google Scholar 

  42. Tack J, Camilleri M, Chang L. Systematic review: cardiovascular safety profile of 5-HT4 agonists developed for gastrointestinal disorders. Aliment Pharmacol Ther. 2012;35:745–767.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Anderson JL, May HT, Blair TL, Muhlestein JB, Horne BD, Carlquist JF. Lack of association of tegaserod with adverse cardiovascular outcomes in a matched case-control study. J Cardiovasc Pharmacol Ther. 2009;14:170–175.

    Article  CAS  PubMed  Google Scholar 

  44. Tack J, Rotondo A, Meulemans A, Thielemans L, Cools M. Randomized clinical trial: a controlled pilot trial of the 5-HT4 receptor agonist Revexepride in patients with symptoms suggestive of gastroparesis. Neurogastroenterol Motil. 2016;28:487–497.

    Article  CAS  PubMed  Google Scholar 

  45. Patterson D, Abell T, Rothstein R, Koch K, Barnett J. A double-blind multicenter comparison of Domperidone and metoclopramide in the treatment of diabetic patients with symptoms of gastroparesis. Am J Gastroenterol. 1999;94:1230–1234.

    CAS  PubMed  Google Scholar 

  46. Dumitrascu DL, Weinbeck M. Domperidone versus metoclopramide in the treatment of diabetic gastroparesis. Am J Gastroenterol. 2000;95:316–317.

    Article  CAS  PubMed  Google Scholar 

  47. Reddymasu SC, Soykan I, McCallum RW. Doperidone: review of pharmacology and clinical applications in gastroenterology. Am J Gastrienterol. 2007;102:2016–2045.

    Article  Google Scholar 

  48. Sugumar A, Singh A, Pasricha PK. A systematic review of the efficacy of Domperidone for the treatment of diabetic gastroparesis. Clin Gastroenterol Hepatol. 2008;6:726–733.

    Article  PubMed  Google Scholar 

  49. Diemunsch P, Grelot L. Potential of substance P antagonists as antiemetics. Drugs. 2000;60:533–546.

    Article  CAS  PubMed  Google Scholar 

  50. Hesketh PJ, Grunberg SM, Gralla RJ, et al. The oral neurokinin-1 antagonist aprepitant for the prevention of chemotherapy-induced nausea and vomiting. J Clin Oncol. 2003;21:4112–4119.

    Article  CAS  PubMed  Google Scholar 

  51. Hesketh PJ, Schnadig ID, Schwartzberg LS, et al. Efficacy of the neurokinin-1 receptor antagonist rolapitant in preventing nausea and vomiting in patients receiving carboplatin-based chemotherapy. Cancer. 2016;122:2418–2425.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Yahata H, Kobayashi H, Sonoda K, et al. Efficacy of aprepitant for the prevention of chemotherapy-induced nausea and vomiting with a moderately emetogenic chemotherapy regimen. Int J Clin Oncol. 2016;21:491–497.

    Article  CAS  PubMed  Google Scholar 

  53. Fahler J, Wall GC, Leman BI. Gastroparesis-associated refractory nausea treated with aprepitant. Ann Pharmacother. 2012;46:e38.

    Article  PubMed  Google Scholar 

  54. Wellington J, Scott B, Kundu S, Stuart P, Koch KL. Effect of endoscopic pyloric therapies for patients with nausea and vomiting and functional obstructive gastroparesis. Auton Neurosci. 2017;202:56–61.

    Article  PubMed  Google Scholar 

  55. Clarke JO, Sharaiha RZ, Kord VA, Lee LA, Kalloo AN, Khashab MA. Through-the-scope transpyloric stent placement improves symptoms and gastric emptying in patients with gastroparesis. Endoscopy. 2013;45(suppl):2.

    Google Scholar 

  56. Khashab MA, Besharati S, Ngamruengphong S, et al. Refractory gastroparesis can be successfully managed with endoscopic transpyloric stent placement and fixation. Gastrointest Endosc. 2015;82:1106–1109.

    Article  PubMed  Google Scholar 

  57. Hibbard ML, Dunst CM, Swanstrom LL. Laparoscopic and endoscopic pyloroplasty for gastroparesis results in sustained symptom improvement. J Gastrointest Surg. 2011;15:1513–1519.

    Article  PubMed  Google Scholar 

  58. Al Shada, Dunst CM, Pescarus R, et al. Laparoscopic pyloroplasty is a safe and effective first-line surgical therapy for refractory gastroparesis. Surg Endosc. 2016;30:1326–1332.

    Article  Google Scholar 

  59. Heckert J, Sankineni A, Hughes WB, Harbison S, Parkman H. Gastric electric stimulation for refractory gastroparesis: a prospective analysis. Dig Dis Sci. 2016;61:169–175.

    Article  Google Scholar 

  60. Sarosiek L, Davis B, Eichler E, McCallum RW. Surgical approaches to treatment of gastroparesis: gastric electrical stimulation, pyloroplasty, total gastrectomy and enteral feeding tubes. Gastroenterol Clin N Am. 2015;44:151–167.

    Article  Google Scholar 

  61. Abel TL, Johnson WD, Kedar A, et al. A double-masked, randomized, placebo-controlled trial of temporary endoscopic mucosal gastric electrical stimulation for gastroparesis. Gastrointest Endosc. 2011;74:496–503.

    Article  Google Scholar 

  62. Deb S, Tang SJ, Abell TL, et al. Development of innovative techniques for the endoscopic implantation and securing of a novel, wireless, miniature gastrostimulator. Gastrointest Endosc. 2012;76:179–184.

    Article  PubMed  PubMed Central  Google Scholar 

  63. Zehetner J, Ravari F, Ayazi S, et al. Minimally invasive surgical approach for the treatment of gastroparesis. Surg Endosc. 2013;27:61–66.

    Article  PubMed  Google Scholar 

  64. Bhayani NH, Sharata AM, Dunst CM, Kurian AA, Reavis KM, Swanstrom LL. End of the road for a dysfunctional end organ: laparoscopic gastrectomy for refractory gastroparesis. J Gastrointest Surg. 2015;19:411–417.

    Article  PubMed  Google Scholar 

  65. Bagloo M, Besseler M, Ude A. Sleeve gastrectomy for the treatment of diabetic gastroparesis. In Proceedings 12th World Congress of Endoscopic Surgery, April 14–17, 2010 Landover, p. 521.

  66. Meyer A, Pallati P, Shaligram A, et al. Partial longitudinal gastrectomy: a novel curative approach for gastroparesis. In Proceedings of the 2012 Annual Meeting of the Society of American Gastrointestinal Endoscopic Surgeons, San Diego, p. 249.

  67. Khashab MA, Stein E, Clarke JO, et al. Gastric peroral endoscopic myotomy for refractory gastroparesis: first human endoscopic pyloromyotomy. Gastrointest Endosc. 2013;78:764–768.

    Article  PubMed  Google Scholar 

  68. Dacha S, Mekaroonkamol P, Li L, et al. Outcomes and quality-of-life assessment after gastric per-oral endoscopic pyloromyotomy. Gastrointest Endosc. 2017. doi:10.1016/j.gie.2017.01.031.

    PubMed  Google Scholar 

  69. Gonazlez JM, Lestelle V, Benezech A, et al. Gastric per-oral endoscopic myotomy with antropyloromyotomy in the treatment of refractory gastroparesis. Gastrointest Endosc. 2017;85:132–139.

    Article  Google Scholar 

  70. Khashab MA, Ngamruengphong S, Carr-Locke D, et al. Gastric per-oral endoscopic myotomy for refractory gastroparesis: results from the first multicenter study on endoscopic pyloromyotomy. Gastrointest Endosc. 2017;85:123–128.

    Article  PubMed  Google Scholar 

  71. Sarna SK. Cyclic motor activity; migrating motor complex. Gastroenterology. 1985;89:894–913.

    Article  CAS  PubMed  Google Scholar 

  72. Broad J, Mukherjee S, Samadi M, Martin J, Dukes G, Sanger G. Regional- and agonist-dependent facilitation of human neurogastrointestinal functions by motilin receptor agonists. Br J Pharmacol. 2012;167:763–774.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Sanger GJ, Furness JB. Ghrelin and motilin receptors as drug targets for gastrointestinal disorders. Nat Rev Gastroenterol Hepatol.. 2016;13:38–48.

    Article  CAS  PubMed  Google Scholar 

  74. Thielemans L, Depoortere I, Perret J, et al. Desensitization of the human motilin receptor by motilides. J Pharmacol Exp Ther. 2005;313:1397–1405.

    Article  CAS  PubMed  Google Scholar 

  75. Verhagen MA, Samsom M, Maes B, Geypens BJ, Ghoos YF, Smout AJ. Effects of a new motilide, ABT-229, on gastric emptying and postprandial antroduodenal motility in healthy volunteers. Aliment Pharmacol Ther. 1997;11:1077–1086.

    Article  CAS  PubMed  Google Scholar 

  76. Talley NJ, Verlinden M, Snape W, et al. Failure of a motilin receptor agonist (ABT-229) to relieve the symptoms of functional dyspepsia in patients with and without delayed gastric emptying. Aliment Pharmacol Ther. 2000;14:1653–1661.

    Article  CAS  PubMed  Google Scholar 

  77. Talley NJ, Verlinden M, Geenen DJ, et al. Effects of a motilin receptor agonist (ABT-229) on upper gastrointestinal symptoms in type 1 diabetes mellitius. Gut. 2001;49:395–401.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. McCallum RW, Cynshi O. Clinical trial: effect of mitemcinal (a motilin agonist) on gastric emptying in patients with gastroparesis. Aliment Pharmacol Ther. 2007;26:1121–1130.

    Article  CAS  PubMed  Google Scholar 

  79. Li JJ, Chao HG, Wang H, et al. Discovery of a potent and novel motilin agonist. J Med Chem. 2004;47:1704–1708.

    Article  CAS  PubMed  Google Scholar 

  80. Hellstrom PM, Tack J, Johnson LV, et al. The pharmacodynamics, safety and pharmacokinetics of single doses of the motilin agonist, camicinal in type 1 diabetes mellitus with slow gastric emptying. Br J Pharmacol. 2016;173:1768–1777.

    Article  PubMed  PubMed Central  Google Scholar 

  81. Barton ME, Otiker T, Johnson LV, et al. A randomized, double-blind, placebo-controlled phase II study (MOT114479) to evaluate the safety and efficacy and dose response of 28 days of orally administered camicinal in diabetics with gastroparesis. Gastroenterology. 2014;146:S-20.

    Article  Google Scholar 

  82. Beattie DT, Higgins DL, Ero MP, et al. An in vitro investigation of the cardiovascular effects of the 5-HT4 receptor selective agonists, Velusetrag and TD-8954. Vascul Pharmacol. 2013;58:150–156.

    Article  CAS  PubMed  Google Scholar 

  83. Manini ML, Camilleri M, Goldberg M, et al. Effects of Velusetrag (TD-5108) on gastrointestinal transit and bowel function in health and pharmacokinetics in heath and constipation. Neurogastroenterol Motil. 2010;22:42-e8.

    Google Scholar 

  84. Yamamoto T, Tajimi M, Takahashi N, Nii T, Zai H. First-in-human study of the novel 5-HT4 agonist, RQ-00000010, demonstrated acceleration of gastric emptying following single and multiple oral administration to healthy human subjects. Gastroenterology. 2013;144:S-736.

    Article  Google Scholar 

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Correspondence to Christopher M. Navas.

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Dr. Lacy is the PI for a gastroparesis research study funded by Vanda; no other conflicts are reported.

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Navas, C.M., Patel, N.K. & Lacy, B.E. Gastroparesis: Medical and Therapeutic Advances. Dig Dis Sci 62, 2231–2240 (2017). https://doi.org/10.1007/s10620-017-4679-7

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