A ghrelin agonist fails to show benefit in patients with diabetic gastroparesis: Let's not throw the baby out with the bath water

Neurogastroenterology and Motility

Volumn 25, Issue 11, 2013, Pages 859-863

  Camilleri, M ^a   Acosta, A ^a  

^a Clinical Enteric Neuroscience Translational and Epidemiological Research Mayo Clinic   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALEMCINAL; GHRELIN; GHRELIN AGONIST; GHRELIN RECEPTOR; GLUCOSE; HORMONE RECEPTOR STIMULATING AGENT; INSULIN; METOCLOPRAMIDE; MOTILIN RECEPTOR AGONIST; PLACEBO; PROMETHAZINE; TZP 102; ULIMORELIN; UNCLASSIFIED DRUG;

AGONIST; BREATH ANALYSIS; DIABETES MELLITUS; DIABETIC GASTROPARESIS; DOWN REGULATION; DRUG EFFICACY; DRUG TREATMENT FAILURE; EPIGASTRIC FULLNESS; HUMAN; LOSS OF APPETITE; MEDICAL DOCUMENTATION; NOTE; PHASE 2 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL (TOPIC); REPEATED DRUG DOSE; STOMACH EMPTYING; STOMACH PARESIS; TACHYPHYLAXIS; VOMITING;

DIABETES MELLITUS, TYPE 1; DIABETES MELLITUS, TYPE 2; FEMALE; GASTRIC EMPTYING; GASTROPARESIS; HUMANS; MACROCYCLIC COMPOUNDS; MALE; RECEPTORS, GHRELIN;

EID: 84884983158     PISSN: 13501925     EISSN: 13652982     Source Type: Journal    
DOI: 10.1111/nmo.12226     Document Type: Note

References (24)

1. Talley NJ, Verlinden M, Geenen DJ et al. Effects of a motilin receptor agonist (ABT-229) on upper gastrointestinal symptoms in type 1 diabetes mellitus: a randomized, double blind, placebo controlled trial. Gut 2001; 49: 395-401.
2. 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: a randomized double-blind placebo-controlled trial. Aliment Pharmacol Ther 2000; 14: 1653-61.
3. Camilleri M. Letter to the Editor: motilin agonists and dyspepsia: throwing out the baby with the bath water. Gut 2002; 51: 612.
4. Camilleri M. The current role of erythromycin in the clinical management of gastric emptying disorders. Am J Gastroenterol 1993; 88: 169-71.
5. Sanger GJ, Westaway SM, Barnes AA et al. GSK962040: a small molecule, selective motilin receptor agonist, effective as a stimulant of human and rabbit gastrointestinal motility. Neurogastroenterol Motil 2009; 21: 657-64, e30-1.
6. Takahashi N, Koba N, Yamamoto T et al. Characterization of a novel, potent, and selective small molecule motilin receptor agonist, RQ-00201894. Gastroenterology 2010; 138: S-713.
7. McCallum RW, Lembo A, Esfandyari T et al. Phase 2b, randomized, double-blind 12-week studies of TZP-102, a ghrelin receptor agonist for diabetic gastroparesis. Neurogastroenterol Motil 2013. doi:10.1111/nmo.12184.
8. Ejskjaer N, Vestergaard ET, Hellström PM et al. Ghrelin receptor agonist (TZP-101) accelerates gastric emptying in adults with diabetes and symptomatic gastroparesis. Aliment Pharmacol Ther 2009; 29: 1179-87.
9. Ejskjaer N, Dimcevski G, Wo J et al. Safety and efficacy of ghrelin agonist TZP-101 in relieving symptoms in patients with diabetic gastroparesis: a randomized, placebo-controlled study. Neurogastroenterol Motil 2010; 22: 1069-e281.
10. Wo JM, Ejskjaer N, Hellström PM et al. Randomised clinical trial: ghrelin agonist TZP-101 relieves gastroparesis associated with severe nausea and vomiting-randomised clinical study subset data. Aliment Pharmacol Ther 2011; 33: 679-88.
11. Bochicchio G, Charlton P, Pezzullo JC, Kosutic G, Senagore A. Ghrelin agonist TZP-101/ulimorelin accelerates gastrointestinal recovery independently of opioid use and surgery type: covariate analysis of phase 2 data. World J Surg 2012; 36: 39-45.
12. Tack J, Peeters T. What comes after macrolides and other motilin stimulants? Gut 2001; 49: 317-8.
13. Szarka LA, Camilleri M, Vella A et al. A stable isotope breath test with a standard meal for abnormal gastric emptying of solids in the clinic and in research. Clin Gastroenterol Hepatol 2008; 6: 635-43.
14. Odunsi ST, Camilleri M, Szarka LA, Zinsmeister AR. Optimizing analysis of stable isotope breath tests to estimate gastric emptying of solids. Neurogastroenterol Motil 2009; 21: 706-e38.
15. Ejskjaer N, Wo JM, Esfandyari T et al. A phase 2a, randomized, double-blind 28-day study of TZP-102 a ghrelin receptor agonist for diabetic gastroparesis. Neurogastroenterol Motil 2013; 25: e140-50. Doi:10.1111/nmo.12064.
16. Camilleri M, Iturrino J, Bharucha AE et al. Performance characteristics of scintigraphic measurement of gastric emptying of solids in healthy participants. Neurogastroenterol Motil 2012; 24: 1076-e562.
17. Parkman HP, Yates K, Hasler WL, et al.; National Institute of Diabetes and Digestive and Kidney Diseases Gastroparesis Clinical Research Consortium. Similarities and differences between diabetic and idiopathic gastroparesis. Clin Gastroenterol Hepatol 2011; 9: 1056-64.
18. Revicki DA, Camilleri M, Kuo B et al. Development and content validity of a gastroparesis cardinal symptom index daily diary. Aliment Pharmacol Ther 2009; 30: 670-80.
19. Revicki DA, Camilleri M, Kuo B, Szarka LA, McCormack J, Parkman HP. Evaluating symptom outcomes in gastroparesis clinical trials: validity and responsiveness of the Gastroparesis Cardinal Symptom Index-Daily Diary (GCSI-DD). Neurogastroenterol Motil 2012; 24: 456-63.
20. Camilleri M, Papathanasopoulos A, Odunsi ST. Actions and therapeutic pathways of ghrelin for gastrointestinal disorders. Nat Rev Gastroenterol Hepatol 2009; 6: 343-52.
21. 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; pii: S1542-3565(13)00578-8. Doi: 10.1016/j.cgh.2013.04.019.
22. 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: 41-8.
23. Kiewiet RM, van Aken MO, van der Weerd K et al. Effects of acute administration of acylated and unacylated ghrelin on glucose and insulin concentrations in morbidly obese subjects without overt diabetes. Eur J Endocrinol 2009; 161: 567-73.
24. Peeters TL. New motilin agonists: a long and winding road. Neurogastroenterol Motil 2006; 18: 1-5.