Pelvic AdhesionsPhase 1/2NCT01701193
A Clinical Study of Alanyl-Glutamine for Reduction of Post-Myomectomy Adhesions
A Phase 1/2 study testing L-Alanyl/L-Glutamine and Physiologic saline in people with Pelvic Adhesions, run by Temple Therapeutics BV at 1 site in Ukraine.
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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Pelvic Adhesions
- What is being tested?
- L-Alanyl/L-Glutamine and Physiologic saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 47 participants
- Where
- 1 siteUkraine
- Study dates
- 15 Feb 2015to 20 Oct 2016
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 13Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
Ukraine1 site
8Surgery and Endoscopy Department of Kharkiv Medical Academy of Postgraduate Education Kharkiv City Clinical Multi-field Hospital
Kharkiv
About this study
Official title: A Randomized Double-Blind Controlled Proof-of-Concept Study of Alanyl-Glutamine for Reduction of Post-Myomectomy Adhesions
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.
Read the 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.
- Conditions
- Pelvic Adhesions
- Being tested
- L-Alanyl/L-Glutamine, Physiologic saline
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
L-Alanyl/L-GlutamineDrug
Also called Evitar
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 salineDrug
Placebo
| Study group | Role | What they receive |
|---|---|---|
| Physiological saline- Laparoscopic | Placebo comparator | Participants receiving intraperitoneal administration of physiological saline at the time of laparoscopic myomectomy. Receives: Drug: Physiologic saline |
| L-Alanyl/L-Glutamine- Laparoscopic | Experimental | Participants receiving intraperitoneal administration of L-Alanyl-L-Glutamine at the time of laparoscopic myomectomy. Receives: Drug: L-Alanyl/L-Glutamine |
| Physiological saline- Laparotomy | Placebo comparator | Participants receiving intraperitoneal administration of physiological saline at the time of myomectomy (laparotomy). Receives: Drug: Physiologic saline |
| L-Alanyl/L-Glutamine- Laparotomy | Experimental | Participants receiving intraperitoneal administration of L-Alanyl-L-Glutamine at the time of myomectomy (laparotomy). Receives: Drug: L-Alanyl/L-Glutamine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants in Which Adhesions Were Prevented.
The American Fertility Society (AFS) grading system for adhesions was used to assess incidence of adhesions. Adhesion prevention was determined through grading of adhesions at the time of myomectomy (initial surgery) and at the time of second look surgery and compared.
Measured: 6-8 weeks
Secondary outcomes (1)
Adverse Events, Adverse Drug Reactions and Clinical Laboratory Abnormalities.
Participants With Treatment-related Adverse Events as Assessed by Clinical Blood Work Abnormalities and Physical Examination.
Measured: 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Oct 2012 (estimated)
- Study start15 Feb 2015
- Primary completion20 Oct 2016
- Study completion20 Oct 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Pelvic AdhesionsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 47 participants (actual)
Sponsor and investigators
- Lead sponsor
- Temple Therapeutics BV
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Donna Chizen, MD, FRCSC, Principal investigator, University of Saskatchewan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01701193
- Sponsor's protocol ID
- Ade002
- Status last verified
- Mar 2021
- First submitted
- 3 Oct 2012
- Last updated
- 7 May 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Double-Blind Controlled Proof-of-Concept Study of Alanyl-Glutamine for Reduction of Post-Myomectomy Adhesions
- ClinicalTrials.gov ID
- NCT01701193
- Acronym / sponsor ID
- Ade002
- Conditions
- Pelvic Adhesions
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 47 participants (actual)
- Lead sponsor
- Temple Therapeutics BVIndustry (pharma, biotech, devices)
- Study start
- 15 Feb 2015 (actual)
- Primary completion
- 20 Oct 2016 (actual)
- Study completion
- 20 Oct 2016 (actual)
- First posted
- 5 Oct 2012 (estimated)
- Results
- Posted 7 May 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Physiological saline- Laparoscopic | Placebo comparator | Drug: Physiologic salineParticipants receiving intraperitoneal administration of physiological saline at the time of laparoscopic myomectomy. |
| L-Alanyl/L-Glutamine- Laparoscopic | Experimental | Drug: L-Alanyl/L-GlutamineParticipants receiving intraperitoneal administration of L-Alanyl-L-Glutamine at the time of laparoscopic myomectomy. |
| Physiological saline- Laparotomy | Placebo comparator | Drug: Physiologic salineParticipants receiving intraperitoneal administration of physiological saline at the time of myomectomy (laparotomy). |
| L-Alanyl/L-Glutamine- Laparotomy | Experimental | Drug: L-Alanyl/L-GlutamineParticipants receiving intraperitoneal administration of L-Alanyl-L-Glutamine at the time of myomectomy (laparotomy). |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| L-Alanyl/L-GlutamineAlso: EvitarSterile 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. | Drug | L-Alanyl/L-Glutamine- Laparoscopic, L-Alanyl/L-Glutamine- Laparotomy |
| Physiologic salinePlacebo | Drug | Physiological saline- Laparoscopic, Physiological saline- Laparotomy |
Primary outcome
Number of Participants in Which Adhesions Were Prevented.
Time frame: 6-8 weeks
The American Fertility Society (AFS) grading system for adhesions was used to assess incidence of adhesions. Adhesion prevention was determined through grading of adhesions at the time of myomectomy (initial surgery) and at the time of second look surgery and compared.
1 secondary outcome
Adverse Events, Adverse Drug Reactions and Clinical Laboratory Abnormalities.
Time frame: 8 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 May 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Donna Chizen, MD, FRCSC principal investigator
University of Saskatchewan
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing L-Alanyl/L-Glutamine and Physiologic saline in people with Pelvic Adhesions, run by Temple Therapeutics BV at 1 site in Ukraine.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 May 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Ukraine. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 7 May 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants in Which Adhesions Were Prevented. (time frame: 6-8 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 May 2021.