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Investigating the Effect of Extracellular Calcium on Oxytocin-induced Human Myometrial Contractility In-vitro

Primary Purpose

Postpartum Hemorrhage

Status
Completed
Phase
Not Applicable
Locations
Canada
Study Type
Interventional
Intervention
Oxytocin
Calcium
Sponsored by
Samuel Lunenfeld Research Institute, Mount Sinai Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Postpartum Hemorrhage focused on measuring Uterine contraction, Oxytocin desensitization

Eligibility Criteria

16 Years - 40 Years (Child, Adult)FemaleAccepts Healthy Volunteers

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 CD or first repeat CD

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 CD
  • 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 CD in labor
  • Patients on medications that could affect myometrial contractility, such as nifedipine, labetolol or magnesium sulphate.

Sites / Locations

  • Mount Sinai Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Active Comparator

Active Comparator

Active Comparator

Active Comparator

Active Comparator

Active Comparator

Arm Label

1.25mM Calcium-NO oxytocin pretreatment

2.5mM Calcium-NO oxytocin pretreatment

5.0mM Calcium-NO oxytocin pretreatment

1.25mM Calcium-WITH oxytocin pretreatment

2.5mM Calcium-WITH oxytocin pretreatment

5.0mM Calcium-WITH oxytocin pretreatment

Arm Description

Outcomes

Primary Outcome Measures

Motility Index
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.

Secondary Outcome Measures

Amplitude of contraction
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.
Frequency of contraction
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.
Integrated area under response curve (AUC)

Full Information

First Posted
October 9, 2014
Last Updated
May 22, 2015
Sponsor
Samuel Lunenfeld Research Institute, Mount Sinai Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT02274454
Brief Title
Investigating the Effect of Extracellular Calcium on Oxytocin-induced Human Myometrial Contractility In-vitro
Official Title
Investigating the Effect of Extracellular Calcium on Oxytocin-induced Human Myometrial Contractility In-vitro
Study Type
Interventional

2. Study Status

Record Verification Date
May 2015
Overall Recruitment Status
Completed
Study Start Date
November 2014 (undefined)
Primary Completion Date
March 2015 (Actual)
Study Completion Date
March 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Samuel Lunenfeld Research Institute, Mount Sinai Hospital

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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 the oxytocin receptor (OTR) found on myometrial cells to cause uterine contraction. It does this by increasing levels of calcium within the myometrial cell, which promotes contraction. Women who require augmentation of labor with intravenous oxytocin because of inadequate labor progression have been shown to be at increased risk of PPH. In-vitro human myometrial models have shown that following prolonged exposure to oxytocin there is desensitization of the myometrium resulting in a significant reduction in contractility upon delivery of further oxytocin. Optimal levels of calcium are very important for contraction of the uterine muscle. Too little calcium results in a reduced contraction. Too much calcium may result in either stronger contractions, or even possibly relaxation of the muscle and therefore a reduced contraction. The investigators currently do not know the effects of calcium on the desensitized uterine muscle. The investigators hypothesize that myometrial contractility following desensitization of the myometrium would be reduced in myometrial samples exposed to low calcium, when compared to normal calcium or high calcium exposure. These results will help in establishing whether myometrial contraction can be augmented by increasing calcium levels within the body, or by optimizing normal physiological calcium levels, in the setting of a augmented prolonged labor, which is at higher risk of poor uterine contraction and PPH.
Detailed Description
The increased incidence of uterine atony and PPH following exogenous oxytocin administration during labor augmentation is related to myometrial OTR desensitization to oxytocin. Calcium is an important messenger required within the uterine muscle cell to result in muscle contraction following administration of oxytocin. A physiological level of calcium is known to provide optimal contractility to normal myometrium. Characterization of the importance of low, normal or high calcium levels in a setting of prolonged exogenous oxytocin administration may provide guidance for the use of exogenous calcium as a uterotonic adjunct; or for the optimization of serum calcium levels during augmented labor. In the clinical setting of failed labor augmentation and OTR desensitization, the role of serum calcium levels is not currently known. The investigators' previously validated in-vitro model provides a solid foundation for the study of myometrial contractility under controlled conditions, without any confounders that could be encountered in clinical settings. The results of this study will provide insight into the effect of low, normal or high calcium levels on the oxytocin pretreated (desensitized) and non-pretreated myometrium. Based on oxytocin dose-response curves after pretreatment to oxytocin and then subsequent exposure to either low, normal or high levels of calcium, the investigators will be able to determine the role of calcium on desensitized myometrium.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Postpartum Hemorrhage
Keywords
Uterine contraction, Oxytocin desensitization

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
41 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1.25mM Calcium-NO oxytocin pretreatment
Arm Type
Active Comparator
Arm Title
2.5mM Calcium-NO oxytocin pretreatment
Arm Type
Active Comparator
Arm Title
5.0mM Calcium-NO oxytocin pretreatment
Arm Type
Active Comparator
Arm Title
1.25mM Calcium-WITH oxytocin pretreatment
Arm Type
Active Comparator
Arm Title
2.5mM Calcium-WITH oxytocin pretreatment
Arm Type
Active Comparator
Arm Title
5.0mM Calcium-WITH oxytocin pretreatment
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
Oxytocin
Other Intervention Name(s)
pitocin
Intervention Description
Experiments will be conducted with some myometrial strips pretreated with oxytocin, and others without any oxytocin pretreatment
Intervention Type
Drug
Intervention Name(s)
Calcium
Intervention Description
Calcium will be applied to the myometrial strips in 3 concentrations; 1.25mM (low), 2.5mM (normal) and 5.0mM (high). Myometrial strips will be either oxytocin pretreated, or non-oxytocin pretreated.
Primary Outcome Measure Information:
Title
Motility Index
Description
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.
Time Frame
8 hours
Secondary Outcome Measure Information:
Title
Amplitude of contraction
Description
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.
Time Frame
8 hours
Title
Frequency of contraction
Description
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.
Time Frame
8 hours
Title
Integrated area under response curve (AUC)
Time Frame
8 hours

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
16 Years
Maximum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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 CD or first repeat CD 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 CD 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 CD in labor Patients on medications that could affect myometrial contractility, such as nifedipine, labetolol or magnesium sulphate.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mrinalini Balki, MD
Organizational Affiliation
MOUNT SINAI HOSPITAL
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mount Sinai Hospital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G1X5
Country
Canada

12. IPD Sharing Statement

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Investigating the Effect of Extracellular Calcium on Oxytocin-induced Human Myometrial Contractility In-vitro

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