The Ghrelin agonist rm-131 accelerates gastric emptying of solids and reduces symptoms in patients with type 1 diabetes mellitus

Andrea Shin, Michael Camilleri, Irene Busciglio, Duane Burton, Steven A. Smith, Adrian Vella, Michael Ryks, Deborah Rhoten, Alan R. Zinsmeister

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Abstract

Background & Aims: RM-131, a synthetic ghrelin agonist, greatly accelerates gastric emptying of solids in patients with type 2 diabetes and delayed gastric emptying (DGE). We investigated the safety and effects of a single dose of RM-131 on gastric emptying and upper gastrointestinal (GI) symptoms in patients with type 1 diabetes and previously documented DGE. Methods: In a double-blind cross-over study, 10 patients with type 1 diabetes (age, 45.7 ± 4.4 y; body mass index, 24.1 ± 1.1 kg/m2) and previously documented DGE were assigned in random order to receive a single dose of RM-131 (100 μg, subcutaneously) or placebo. Thirty minutes later, they ate a radiolabeled solid-liquid meal containing EggBeaters (ConAgra Foods, Omaha, NE), and then underwent 4 hours of gastric emptying and 6 hours of colonic filling analyses by scintigraphy. Upper GI symptoms were assessed using a daily diary, gastroparesis cardinal symptom index (total GCSI-DD) and a combination of nausea, vomiting, fullness, and pain (NVFP) scores (each rated on a 0-5 scale). Results: At screening, participants' mean level of hemoglobin A1c was 9.1% ± 0.5%; their total GCSI-DD score was 1.66 ± 0.38 (median, 1.71), and their total NVFP score was 1.73 ± 0.39 (median, 1.9). The t1/2 of solid gastric emptying was 84.9 ± 31.6 minutes when subjects were given RM-131 and 118.7 ± 26.7 when they were given a placebo. The median difference (δ)was 33.9 minutes (interquartile range [IQR] -12, -49), or -54.7% (IQR, -21%,-110%). RM-131 decreased gastric retention of solids at 1 hour (P=.005) and 2 hours (P=.019). Numeric differences in t1/2 for gastric emptying of liquids, solid gastric emptying lag time, and colonic filling at 6 hours were not significant. Total GCSI-DD scores were 0.79 on placebo (IQR, 0.75, 2.08) and 0.17 on RM-131 (IQR, 0.00, 0.67; P=.026); NVFP scores were lower on RM-131 (P=.041). There were no significant adverse effects. Conclusions: RM-131 significantly accelerates gastric emptying of solids and reduces upper GI symptoms in patients with type 1 diabetes and documented DGE.

Original languageEnglish (US)
Pages (from-to)1453-1459
Number of pages7
JournalClinical Gastroenterology and Hepatology
Volume11
Issue number11
DOIs
StatePublished - Nov 2013

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Ghrelin
Gastric Emptying
Type 1 Diabetes Mellitus
Nausea
Vomiting
Placebos
Pain
Gastroparesis
relamorelin
Radionuclide Imaging
Cross-Over Studies
Type 2 Diabetes Mellitus
Meals
Stomach
Hemoglobins
Body Mass Index

Keywords

  • Clinical Trial
  • Drug
  • Gastroparesis
  • Prokinetic

ASJC Scopus subject areas

  • Gastroenterology
  • Hepatology

Cite this

The Ghrelin agonist rm-131 accelerates gastric emptying of solids and reduces symptoms in patients with type 1 diabetes mellitus. / Shin, Andrea; Camilleri, Michael; Busciglio, Irene; Burton, Duane; Smith, Steven A.; Vella, Adrian; Ryks, Michael; Rhoten, Deborah; Zinsmeister, Alan R.

In: Clinical Gastroenterology and Hepatology, Vol. 11, No. 11, 11.2013, p. 1453-1459.

Research output: Contribution to journalArticle

Shin, Andrea ; Camilleri, Michael ; Busciglio, Irene ; Burton, Duane ; Smith, Steven A. ; Vella, Adrian ; Ryks, Michael ; Rhoten, Deborah ; Zinsmeister, Alan R. / The Ghrelin agonist rm-131 accelerates gastric emptying of solids and reduces symptoms in patients with type 1 diabetes mellitus. In: Clinical Gastroenterology and Hepatology. 2013 ; Vol. 11, No. 11. pp. 1453-1459.
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abstract = "Background & Aims: RM-131, a synthetic ghrelin agonist, greatly accelerates gastric emptying of solids in patients with type 2 diabetes and delayed gastric emptying (DGE). We investigated the safety and effects of a single dose of RM-131 on gastric emptying and upper gastrointestinal (GI) symptoms in patients with type 1 diabetes and previously documented DGE. Methods: In a double-blind cross-over study, 10 patients with type 1 diabetes (age, 45.7 ± 4.4 y; body mass index, 24.1 ± 1.1 kg/m2) and previously documented DGE were assigned in random order to receive a single dose of RM-131 (100 μg, subcutaneously) or placebo. Thirty minutes later, they ate a radiolabeled solid-liquid meal containing EggBeaters (ConAgra Foods, Omaha, NE), and then underwent 4 hours of gastric emptying and 6 hours of colonic filling analyses by scintigraphy. Upper GI symptoms were assessed using a daily diary, gastroparesis cardinal symptom index (total GCSI-DD) and a combination of nausea, vomiting, fullness, and pain (NVFP) scores (each rated on a 0-5 scale). Results: At screening, participants' mean level of hemoglobin A1c was 9.1{\%} ± 0.5{\%}; their total GCSI-DD score was 1.66 ± 0.38 (median, 1.71), and their total NVFP score was 1.73 ± 0.39 (median, 1.9). The t1/2 of solid gastric emptying was 84.9 ± 31.6 minutes when subjects were given RM-131 and 118.7 ± 26.7 when they were given a placebo. The median difference (δ)was 33.9 minutes (interquartile range [IQR] -12, -49), or -54.7{\%} (IQR, -21{\%},-110{\%}). RM-131 decreased gastric retention of solids at 1 hour (P=.005) and 2 hours (P=.019). Numeric differences in t1/2 for gastric emptying of liquids, solid gastric emptying lag time, and colonic filling at 6 hours were not significant. Total GCSI-DD scores were 0.79 on placebo (IQR, 0.75, 2.08) and 0.17 on RM-131 (IQR, 0.00, 0.67; P=.026); NVFP scores were lower on RM-131 (P=.041). There were no significant adverse effects. Conclusions: RM-131 significantly accelerates gastric emptying of solids and reduces upper GI symptoms in patients with type 1 diabetes and documented DGE.",
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T1 - The Ghrelin agonist rm-131 accelerates gastric emptying of solids and reduces symptoms in patients with type 1 diabetes mellitus

AU - Shin, Andrea

AU - Camilleri, Michael

AU - Busciglio, Irene

AU - Burton, Duane

AU - Smith, Steven A.

AU - Vella, Adrian

AU - Ryks, Michael

AU - Rhoten, Deborah

AU - Zinsmeister, Alan R.

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N2 - Background & Aims: RM-131, a synthetic ghrelin agonist, greatly accelerates gastric emptying of solids in patients with type 2 diabetes and delayed gastric emptying (DGE). We investigated the safety and effects of a single dose of RM-131 on gastric emptying and upper gastrointestinal (GI) symptoms in patients with type 1 diabetes and previously documented DGE. Methods: In a double-blind cross-over study, 10 patients with type 1 diabetes (age, 45.7 ± 4.4 y; body mass index, 24.1 ± 1.1 kg/m2) and previously documented DGE were assigned in random order to receive a single dose of RM-131 (100 μg, subcutaneously) or placebo. Thirty minutes later, they ate a radiolabeled solid-liquid meal containing EggBeaters (ConAgra Foods, Omaha, NE), and then underwent 4 hours of gastric emptying and 6 hours of colonic filling analyses by scintigraphy. Upper GI symptoms were assessed using a daily diary, gastroparesis cardinal symptom index (total GCSI-DD) and a combination of nausea, vomiting, fullness, and pain (NVFP) scores (each rated on a 0-5 scale). Results: At screening, participants' mean level of hemoglobin A1c was 9.1% ± 0.5%; their total GCSI-DD score was 1.66 ± 0.38 (median, 1.71), and their total NVFP score was 1.73 ± 0.39 (median, 1.9). The t1/2 of solid gastric emptying was 84.9 ± 31.6 minutes when subjects were given RM-131 and 118.7 ± 26.7 when they were given a placebo. The median difference (δ)was 33.9 minutes (interquartile range [IQR] -12, -49), or -54.7% (IQR, -21%,-110%). RM-131 decreased gastric retention of solids at 1 hour (P=.005) and 2 hours (P=.019). Numeric differences in t1/2 for gastric emptying of liquids, solid gastric emptying lag time, and colonic filling at 6 hours were not significant. Total GCSI-DD scores were 0.79 on placebo (IQR, 0.75, 2.08) and 0.17 on RM-131 (IQR, 0.00, 0.67; P=.026); NVFP scores were lower on RM-131 (P=.041). There were no significant adverse effects. Conclusions: RM-131 significantly accelerates gastric emptying of solids and reduces upper GI symptoms in patients with type 1 diabetes and documented DGE.

AB - Background & Aims: RM-131, a synthetic ghrelin agonist, greatly accelerates gastric emptying of solids in patients with type 2 diabetes and delayed gastric emptying (DGE). We investigated the safety and effects of a single dose of RM-131 on gastric emptying and upper gastrointestinal (GI) symptoms in patients with type 1 diabetes and previously documented DGE. Methods: In a double-blind cross-over study, 10 patients with type 1 diabetes (age, 45.7 ± 4.4 y; body mass index, 24.1 ± 1.1 kg/m2) and previously documented DGE were assigned in random order to receive a single dose of RM-131 (100 μg, subcutaneously) or placebo. Thirty minutes later, they ate a radiolabeled solid-liquid meal containing EggBeaters (ConAgra Foods, Omaha, NE), and then underwent 4 hours of gastric emptying and 6 hours of colonic filling analyses by scintigraphy. Upper GI symptoms were assessed using a daily diary, gastroparesis cardinal symptom index (total GCSI-DD) and a combination of nausea, vomiting, fullness, and pain (NVFP) scores (each rated on a 0-5 scale). Results: At screening, participants' mean level of hemoglobin A1c was 9.1% ± 0.5%; their total GCSI-DD score was 1.66 ± 0.38 (median, 1.71), and their total NVFP score was 1.73 ± 0.39 (median, 1.9). The t1/2 of solid gastric emptying was 84.9 ± 31.6 minutes when subjects were given RM-131 and 118.7 ± 26.7 when they were given a placebo. The median difference (δ)was 33.9 minutes (interquartile range [IQR] -12, -49), or -54.7% (IQR, -21%,-110%). RM-131 decreased gastric retention of solids at 1 hour (P=.005) and 2 hours (P=.019). Numeric differences in t1/2 for gastric emptying of liquids, solid gastric emptying lag time, and colonic filling at 6 hours were not significant. Total GCSI-DD scores were 0.79 on placebo (IQR, 0.75, 2.08) and 0.17 on RM-131 (IQR, 0.00, 0.67; P=.026); NVFP scores were lower on RM-131 (P=.041). There were no significant adverse effects. Conclusions: RM-131 significantly accelerates gastric emptying of solids and reduces upper GI symptoms in patients with type 1 diabetes and documented DGE.

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