Effect of Magnesium Sulphate Pre-exposure on Oxytocin-induced Contractility in Desensitized Human Myometrium - an in Vitro Study

July 12, 2017 updated by: Samuel Lunenfeld Research Institute, Mount Sinai Hospital

Postpartum hemorrhage (PPH) is the loss of more than 500ml of blood within 24 hours after delivery. It is a major cause of maternal morbidity and mortality across the globe.

Oxytocin is a naturally-occurring hormone that causes the uterus to contract, thereby causing labor. A synthetic form of oxytocin is used in obstetric medicine in the same way. It causes the uterus to contract by acting at the oxytocin receptor (OTR). It is used for both the prevention and the treatment of PPH. By causing the uterus to contract, it constricts the blood vessels within it, thus reducing bleeding.

Oxytocin is also used to augment labor in women with slow labor progression. Desensitization of the OTR after prolonged exposure to oxytocin occurs, leading to reduced contractions of the uterus with the same doses of oxytocin. This has been demonstrated in previous studies done by the investigators. The resultant need for a higher oxytocin dose to cause adequate uterine contraction has also been demonstrated in laboring women having received oxytocin for labor augmentation.

Magnesium sulphate (MgSO4) is widely used within obstetric medicine. It is used for seizure prevention and treatment in preeclampsia and eclampsia, and is used for fetal neuroprotection in preterm labor, to reduce the risk of cerebral palsy. It is well-known to have a relaxant effect on uterine muscle, and as such, has been used as a tocolytic agent in preterm labour to prevent premature contractions and premature delivery. The effect of MgSO4 on contractions in oxytocin pre-treated myometrium has not been fully elucidated with human lab studies. There are suggestions it may lead to increased oxytocin requirements or increased postpartum hemorrhage (PPH) in preeclamptic patients. This bears significance in the preeclamptic and eclamptic populations who are likely to be receiving MgSO4 in combination with oxytocin.

The investigators hypothesize that MgSO4 will reduce uterine contractions in oxytocin pre-treated myometrium, as well as untreated myometrium, and higher oxytocin doses will be needed to produce equivalent contractions. This will help us to better understand the implications of the use of these drugs together in the clinical setting.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

MgSO4 is known to cause relaxation of uterine muscle in the doses used for preeclampsia and eclampsia and fetal neuroprotection. In these clinical settings, after delivery, oxytocin is often given to prevent or treat PPH. There is evidence that patients with preeclampsia already have a higher risk of PPH than non-preeclamptic patients. In the presence of the effects of MgSO4 treatment on the uterus, PPH could be worse in theory. If patients have had oxytocin-augmented labor, then the desensitization effect on the uterus also comes into play. Performing this study in vitro will allow us to assess the effects on the uterine muscle of MgSO4 in oxytocin-desensitized tissue samples.

Scientific evidence on pregnancy outcomes in these patients is timely and important. A study of myometrial contractility under controlled conditions is likely to provide us with information on the interactions between oxytocin and MgSO4 that occurs in many clinical scenarios, eliminating any confounders that could be encountered in clinical settings. The investigators hope to determine the myometrial contraction patterns induced by oxytocin in the presence of MgSO4, including in myometrial specimens pre-treated with oxytocin plus MgSO4, to mimic the clinical scenarios in preeclampsia and fetal neuroprotection. This will expand the depth of our understanding of the desensitization phenomenon, and could provide valuable insight into the mechanism responsible for PPH in these patient populations. This study will form a basis for future modifications in oxytocin augmentation regimens and pharmacotherapy for control of uterine atony and PPH in these patient populations being simultaneously treated with MgSO4.

Study Type

Interventional

Enrollment (Actual)

26

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

14 years to 38 years (Child, Adult)

Accepts Healthy Volunteers

No

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 delivery or first repeat Cesarean delivery under spinal anesthesia

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 delivery
  • 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 medical/pregnancy related conditions, such as diabetes, preeclampsia and essential hypertension

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 (no oxytocin) pretreatment
The myometrial samples are bathed in physiological saline solution (PSS).
Active Comparator: Magnesium Sulphate
The myometrial samples are bathed in a 3.5mM magnesium sulphate solution.
Drug: Magnesium Sulphate
Magnesium sulphate, 3.5mM solution
Active Comparator: Magnesium Sulphate + oxytocin
The myometrial samples are bathed in a 3.5mM magnesium sulphate plus 10-5M oxytocin solution.
Drug: Magnesium Sulphate
Magnesium sulphate, 3.5mM solution
Drug: Oxytocin
Oxytocin, 10-5M solution
Other Names:
  • pitocin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Motility Index
Time Frame: 2 hours

Motility index (MI) takes into account both the amplitude and frequency of the myometrial contraction. It is a calculated outcome, based on the formula: frequency/(10 x amplitude).

The analysis is undertaken by attaching myometrial strips between an isometric force transducer and the base of an organ bath chamber.
2 hours

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Amplitude of contraction
Time Frame: 2 hours
The maximum extent of uterine muscle contraction, measured in grams (g). The analysis is undertaken by attaching myometrial strips between an isometric force transducer and the base of an organ bath chamber.
2 hours
Frequency of contraction
Time Frame: 2 hours

The number of contractions in uterine muscle (myometrium) over 10 minutes, spontaneously and in response to an agonist.

The analysis is undertaken by attaching myometrial strips between an isometric force transducer and the base of an organ bath chamber.
2 hours
Integrated area under response curve (AUC)
Time Frame: 2 hours
2 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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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

January 1, 2016

Primary Completion (Actual)

April 1, 2017

Study Completion (Actual)

April 1, 2017

Study Registration Dates

First Submitted

January 4, 2016

First Submitted That Met QC Criteria

January 4, 2016

First Posted (Estimate)

January 6, 2016

Study Record Updates

Last Update Posted (Actual)

July 17, 2017

Last Update Submitted That Met QC Criteria

July 12, 2017

Last Verified

July 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 16-01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

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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