Recovery of Oxytocin Responsiveness in Pregnant Human Myometrial Explants After Oxytocin-Induced Desensitization

May 22, 2015 updated by: Samuel Lunenfeld Research Institute, Mount Sinai Hospital

Postpartum hemorrhage (PPH) is a leading cause of maternal morbidity and mortality worldwide and is caused most commonly by poor uterine muscle tone after delivery. The first line agent used in the prevention and treatment of PPH is oxytocin, which acts by binding with oxytocin receptors (OTR) found on myometrial cells to cause uterine contraction.

Women who require augmentation of labour with oxytocin because of inadequate labour progression are at increased risk of PPH because they have received intravenous oxytocin which exposes the uterus (and OTR) to doses greater than would normally be found without medical intervention. This exposure results in OTR desensitization and decreased uterine sensitivity to oxytocin which may lead to the use of much higher doses of oxytocin (up to 9x) or other agents for preventing and treating PPH with the potential for causing serious drug-related morbidity or fatality to the mother.

Currently, in women who have failed labour augmentation and need to have a Cesarean delivery, it is not known if it would be beneficial to wait a certain period of time after discontinuing intravenous oxytocin before proceeding with the operation. The goal of the waiting time would be to allow the OTRs to recover and resensitize the uterus to the effects of oxytocin to avoid the need for high doses or additional uterus-contracting agents.

Our hypothesis is that there will be a positive correlation between the magnitude of recovery of the myometrium's response to oxytocin and the time elapsed from the desensitizing oxytocin pretreatment (simulated labour augmentation).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The investigators have previously established an in vitro model of labour augmentation and myometrial desensitization using pregnant human myometrium and an isometric tension recording device. The investigators propose to use this model in order to characterize the time course of recovery of oxytocin-desensitized myometrium to oxytocin sensitivity. These results will help in establishing whether myometrial recovery can occur within a clinically relevant time period, how much sensitivity is recovered, and the duration required.

In the clinical setting of failed labour augmentation and OTR desensitization, it is not known if it is beneficial to wait a certain period of time after discontinuing intravenous oxytocin before proceeding to Cesarean section to allow for resensitization of the myometrium to oxytocin. The results of this study will provide insight into the time course of recovery of the myometrium using an in vitro model of failed labour augmentation. Based on the oxytocin dose-response curves after variable periods of time of "rest", the investigators will be able to determine the degree of recovery of myometrial contractility over time and whether this will occur in a clinically relevant time period for implementation into clinical practice.

Study Type

Interventional

Enrollment (Actual)

22

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G1X5
        • Mount Sinai Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 55 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Patients who give written consent to participate in this study
  • Patients with gestational age 37-41 weeks
  • Non-laboring patients, not exposed to exogenous oxytocin
  • Patients requiring primary Cesarean section or first repeat Cesarean section

Exclusion Criteria:

  • Patients who refuse to give written informed consent
  • Patients who require general anesthesia
  • Patients who had previous uterine surgery or more than one previous Cesarean section
  • Patients with a multiple pregnancy (more than one fetus)
  • Patients with any condition predisposing to uterine atony and postpartum hemorrhage, such as abnormal placentation, multiple gestation, preeclampsia, macrosomia, polyhydramnios, uterine fibroids, bleeding diathesis, chorioamnionitis, or a previous history of postpartum bleeding
  • Emergency Cesarean section in labor
  • Patients with bleeding disorders

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
No Intervention: Control
A control sample from each patient (no oxytocin applied) will be measured concurrently with samples treated with oxytocin.
Experimental: Oxytocin
Samples from each patient will be exposed to oxytocin and then allowed to rest for 30, 60 or 90 minutes.
Drug: Oxytocin
Oxytocin, 10-10mol/L to 10-5mol/L
Other Names:
  • Pitocin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Amplitude of contraction
Time Frame: 2-4 hours
2-4 hours

Secondary Outcome Measures

Outcome Measure
Time Frame
frequency of contraction
Time Frame: 2-4 hours
2-4 hours
Integrated area under response curve (AUC)
Time Frame: 2-4 hours
2-4 hours
basal tone
Time Frame: 2-4 hours
2-4 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Samuel Lunenfeld Research Institute, Mount Sinai Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2013

Primary Completion (Actual)

June 1, 2014

Study Completion (Actual)

June 1, 2014

Study Registration Dates

First Submitted

January 29, 2014

First Submitted That Met QC Criteria

January 29, 2014

First Posted (Estimate)

January 31, 2014

Study Record Updates

Last Update Posted (Estimate)

May 27, 2015

Last Update Submitted That Met QC Criteria

May 22, 2015

Last Verified

May 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 14-01

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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