The published studies examined gastric emptying, colonic transit, gastric contractility and postoperative gastrointestinal endpoints.
Ipamorelin and Gastrointestinal Motility Research
Researchers investigated ipamorelin in gastrointestinal motility because it acts as a ghrelin receptor agonist. The published Ipamorelin studies examined gastrointestinal motility in postoperative rat models.
Gastric emptying refers to the movement of stomach contents out of the stomach. Intestinal transit refers to the movement of material through the gastrointestinal tract.
Ipamorelin and Gastric Emptying in Experimental Models
The study used fasted adult male rats that underwent laparotomy and intestinal manipulation. Gastric emptying was then measured by the percentage of recovered radioactivity remaining in the stomach 15 minutes after the test meal. Surgery delayed gastric emptying, with 78% ± 5% of the meal remaining in vehicle-treated animals.
Ipamorelin significantly accelerated gastric emptying in the surgical model. In the Ipamorelin group, 52% ± 11% of the meal remained in the stomach, compared with 78% ± 5% in vehicle treated rats. Nonsurgical controls had 44% ± 6% remaining.
The researchers also tested isolated gastric fundus tissue in an organ bath. Surgery and intestinal manipulation reduced contractile responses to acetylcholine and electrical field stimulation. Ipamorelin and ghrelin reversed these changes in the isolated gastric tissue.
Ipamorelin and Intestinal Transit in Experimental Models
The 2009 rat study measured post-surgical colonic transit using the time to the first bowel movement. A dye marker was infused into the proximal colon after laparotomy and intestinal manipulation.
A single exposure to Ipamorelin decreased the time to the first bowel movement compared with vehicle. The study reported no change in cumulative fecal output after the single exposure.
The study also examined repeated exposure. Under this experimental condition, Ipamorelin increased cumulative fecal pellet output.
Gastrointestinal Mechanisms Investigated With Ipamorelin
The gastric tissue experiments identified ghrelin receptor-mediated activity as part of the proposed mechanism. Ipamorelin reversed the inhibition of gastric smooth-muscle responses produced by abdominal surgery and intestinal manipulation. Ghrelin produced similar effects in the tissue experiments.
The researchers concluded that the gastric response involved stimulation of gastric contractility through a ghrelin receptor-mediated mechanism involving cholinergic excitatory neurons.
Human Research on Ipamorelin in a Phase II Study
The Phase II human study was a prospective, randomized, controlled, multicenter, double-blind and placebo-controlled trial. It included adults undergoing small or large bowel resection through open or laparoscopic surgery.
The study enrolled 117 patients. The safety and modified intent-to-treat populations each included 114 patients. The key efficacy endpoint was the time from the first study-drug exposure to tolerance of a standardized solid meal.
Findings From the Human Ipamorelin Study
The median time to first tolerated meal was 25.3 hours with Ipamorelin and 32.6 hours with placebo. The difference was not statistically significant (P = 0.15).
The study reported no significant differences between Ipamorelin and placebo in the key and secondary efficacy analyses. The authors described the trial as a proof-of-concept Phase II study and noted that it was small and included patients with a broad range of underlying conditions.
Limitations of Current Ipamorelin Gastrointestinal Research
The published evidence comes from different research settings. The 2009 and 2012 studies used postoperative rat models, while the Phase II study involved patients undergoing bowel resection.
The endpoints also differed between studies. Animal experiments measured colonic transit, fecal pellet output, gastric emptying and gastric contractility. The human study used tolerance of a standardized solid meal as its key efficacy endpoint.
The human study was relatively small and included patients with a broad range of underlying conditions. Its primary efficacy endpoint did not reach statistical significance.
Research Category CTA
For additional research information, explore the Ipamorelin research peptide category at Direct SARMs.
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References
- Venkova K, Mann W, Nelson R, Greenwood-Van Meerveld B. Efficacy of ipamorelin, a novel ghrelin mimetic, in a rodent model of postoperative ileus. J Pharmacol Exp Ther. 2009 Jun;329(3):1110-6. PubMed ↗
- Greenwood-Van Meerveld B, Tyler K, Mohammadi E, Pietra C. Efficacy of ipamorelin, a ghrelin mimetic, on gastric dysmotility in a rodent model of postoperative ileus. J Exp Pharmacol. 2012 Oct 19;4:149-55. PubMed ↗
- Beck DE, Sweeney WB, McCarter MD; Ipamorelin 201 Study Group. Prospective, randomized, controlled, proof-of-concept study of the Ghrelin mimetic ipamorelin for the management of postoperative ileus in bowel resection patients. Int J Colorectal Dis. 2014 Dec;29(12):1527-34. PubMed ↗
