A randomized double-blind controlled proof-of-concept study of alanyl-glutamine for reduction of post-myomectomy adhesions

Study Objective: To test the hypothesis that intraperitoneal instillation of a single bolus dose of L-alanyl-L-gluta-mine (AG) will reduce the incidence, extent and/or severity of adhesions following myomectomy and establish preliminary safety and tolerability of AG in humans.Design: Phase 1,2 Randomized, double-blind, placebo-controlled study (DBRCT).Setting: Tertiary care gynecology surgical centre.Patients: Thirty-eight women who underwent myomectomies by laparoscopy (N = 38; AG-19 vs Placebo-19) or laparotomy (N = 10; AG-5 vs Placebo-5) with a scheduled second-look laparoscopy (SLL) 6-8 weeks later. Thirty-two patients in the laparoscopy arm completed SLL.Interventions: Bolus dose of AG or normal saline solution control (0.9% NaCl) administered intraperitoneally immediately prior to suture closure of the laparoscopic ports. The average dose was 170 mL of AG or control based on a dosing scheme of 1 g/kg bodyweight.Measurements: Digital recordings obtained for all procedures. The primary endpoint was reduction in the inci-dence, severity and extent of post-operative adhesions analyzed by intention-to-treat (ITT) approach. Three independent, blinded reviewers evaluated all operative video recordings to assess presence of adhesions. Post -hoc analysis assessed presence or absence of adhesions in the peritoneal cavity. Secondary endpoints assessed safety and tolerability of AG.Main results: Administration of AG reduced the incidence, severity and/or extent of post-operative adhesions (p = 0.046). The presence of adhesions in the AG group was lower than in the Control group (p = 0.041). Adhesion improvement was achieved in 15 of 15 (100%) in the AG group versus 5 of 17 (29.6%) in the placebo group. No serious adverse events were reported. No differences in safety parameters were observed.Conclusions: Intraperitoneal L-alanyl-L-glutamine reduced adhesion formation in all patients following laparo-scopic myomectomy. Complete absence of adhesions was achieved at all abdominal sites in 93% of patients. Results confirm AG's known effects on cellular mechanisms of adhesiogenesis and lay the foundation for new adhesion prophylaxis research and treatment.

Automated summary

The study aimed to test the hypothesis that intraperitoneal instillation of L-alanyl-L-glutamine (AG) could reduce the incidence, extent, and severity of adhesions following myomectomy, and to establish the safety and tolerability of AG in humans. The results showed that AG can reduce the incidence, extent, and severity of post-operative adhesions. No serious adverse events were reported in the AG group. These findings confirm the effects of AG on the cellular mechanisms of adhesiogenesis and lay the foundation for further research and treatment in adhesion prophylaxis.