Clinical trial NCT01701193
Conditions: Pelvic Adhesions
Sponsor: Temple Therapeutics BV
Start date: 2015-02-15; Completion date: 2016-10-20
Enrollment: 47 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This study evaluates whether L-Alanyl-L-Glutamine can reduce the incidence, extent and severity of adhesions after myomectomy. Half of the participants will receive L-Alanyl-L-Glutamine and the other half of participants will receive a saline placebo at the time of myomectomy.

Detailed description:
The myriad medical and financial burdens of post-operative adhesions are well documented; however, treatment options are limited and controversial. Implantable physical barriers to prevent adhesions are commercially available, but most trials have failed to demonstrate compelling evidence to support widespread use. In recent years, advances have been made in our understanding of the cellular mechanisms underlying adhesiogenesis, raising the prospect of targeting these pathways to prevent post-surgical adhesions. However, to date, no drug has received regulatory approval for this purpose in any jurisdiction. Our study was designed to evaluate the efficacy and safety of a single intraoperative intraperitoneal dose of L-Alanyl-L-Glutamine (AG), an agent which has been shown to act upon key mediators in the adhesion formation pathway.

Methods: This was a randomized, double-blind, placebo-controlled study (DBRCT) of 47 women who underwent myomectomies by laparoscopy (N=37; AG-18 vs Placebo-19) or laparotomy (N=10; AG-5 vs Placebo-5) with a scheduled clinically necessary second-look laparoscopy (SLL) 6 - 8 weeks later. Digital recordings were obtained for all procedures. The primary endpoint was reduction in the incidence, severity and extent of post-operative adhesions, as analyzed by intention-to-treat (ITT) approach.

Three independent, blinded reviewers evaluated the operative video recordings to assess for presence of adhesions. Secondary endpoints assessed the safety and tolerability of AG. Post-hoc analysis assessed presence or absence of adhesions in the peritoneal cavity. Patients included those with previous history of surgery, endometriosis, and adhesiolysis was permitted at myomectomy.

Arms: arm 1: Participants receiving intraperitoneal administration of physiological saline at the time of laparoscopic myomectomy. arm 2: Participants receiving intraperitoneal administration of L-Alanyl-L-Glutamine at the time of laparoscopic myomectomy. arm 3: Participants receiving intraperitoneal administration of physiological saline at the time of myomectomy (laparotomy). arm 4: Participants receiving intraperitoneal administration of L-Alanyl-L-Glutamine at the time of myomectomy (laparotomy).
Interventions: intervention 1: L-Alanyl/L-Glutamine intervention 2: Physiologic saline
Intervention descriptions: intervention 1: Sterile solution of L-Alanyl-L-Glutamine, 400mg/mL in water for injection. It is dosed at 1g/kg of body weight and is instilled into the peritoneum at the time of surgery. The active ingredient, glutamine, is a conditionally essential amino acid component of nutritional supplements. intervention 2: Placebo

Protocol documents: