A Randomized Double-Blind Controlled Study of Alanyl-Glutamine for Adhesion Reduction

Adhesion; Peritoneum Clinical Trial

Official title:

A Randomized Double-Blind Controlled Proof-of-Concept Study of Alanyl-Glutamine for Reduction of Post-Myomectomy Adhesions

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04250467
• Other study ID #: ADE002
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: February 15, 2015
• Est. completion date: October 20, 2016

Study information

• Verified date: December 2020
• Source: Temple Therapeutics BV
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 38 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 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 39
• Est. completion date: October 20, 2016
• Est. primary completion date: October 20, 2016
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Subjects are female

• Subjects are 18 years of age or older at the time of consent

• Subjects have a BMI between 17-40

• Subjects must have signed informed consent form

• Subjects have a preoperative diagnosis of uterine fibroids and plan to have a myomectomy completed surgically as part of their standard of care

• Subjects must have a physical examination and compliance assessment

Exclusion Criteria:

• Subjects whose BMI is outside the range of 17-40

• Subjects participating in another clinical trial with a drug or device

• Subjects who have participated in a clinical trial with a drug or device within 30 days prior to this study

• Subjects with suspected or diagnosed pregnancy

• Subjects with suspected intraabdominal infection

• Subjects who are immunocompromised

• Subjects diagnosed with cancer

• Subjects treated with hemostatic agents (e.g. fibrin sealant, collagen, oxidized cellulose)

• Subjects treated with adhesion prevention agents other than the Anti-Adhesion product (APP) (e.g. Intergel ® Adhesion Prevention Solution, Seprafilm ® Membrane)

• Subjects taking anti-epileptic medication

• Subjects who have been treated with Methotrexate or other chemotherapeutics agents

• Subjects with an American Fertility Society score of Stage D at the time of myomectomy as determined by the surgeon

• Positive viral serology screening results for hepatitis B surface antigen, antibodies to hepatitis C virus or human immunodeficiency

Related Conditions & MeSH terms

• Adhesion; Peritoneum
• Tissue Adhesions

Intervention

Drug:
• L-Alanyl/L-Glutamine
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.
• Physiologic saline

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Temple Therapeutics BV

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Efficacy of L-Alanyl-L-Glutamine	A statistically significant reduction in the incidence, extent and severity of adhesions observed in the L-Alanyl-L-Glutamine treated group compared to the saline control group using the American Fertility Society grading system.	6-8 weeks
Secondary	Number of participants with treatment-related adverse events as assessed by clinical blood work abnormalities and physical examination.	Adverse events, adverse drug reactions and clinical laboratory abnormalities will be analyzed be using the chi-square test or Fisher's Exact test. Any continuous measurement in physical examination and clinical laboratory will be analyzed by t-test or Wilcoxon rank test.	8 weeks