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

NCT02274454 | Completed

• 1 other identifier: 14-02
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 1

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.

Conditions

Postpartum Hemorrhage

Keywords

Uterine contraction; Oxytocin desensitization

Outcome Measures

Primary Outcomes (1)

• 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.

  8 hours

Secondary Outcomes (3)

• Amplitude of contraction

  8 hours

• Frequency of contraction

  8 hours

• Integrated area under response curve (AUC)

  8 hours

Study Arms (6)

1.25mM Calcium-NO oxytocin pretreatment

ACTIVE COMPARATOR

Drug: Calcium

2.5mM Calcium-NO oxytocin pretreatment

ACTIVE COMPARATOR

Drug: Calcium

5.0mM Calcium-NO oxytocin pretreatment

ACTIVE COMPARATOR

Drug: Calcium

1.25mM Calcium-WITH oxytocin pretreatment

ACTIVE COMPARATOR

Drug: Oxytocin; Drug: Calcium

2.5mM Calcium-WITH oxytocin pretreatment

ACTIVE COMPARATOR

Drug: Oxytocin; Drug: Calcium

5.0mM Calcium-WITH oxytocin pretreatment

ACTIVE COMPARATOR

Drug: Oxytocin; Drug: Calcium

Interventions

Oxytocin DRUG

Experiments will be conducted with some myometrial strips pretreated with oxytocin, and others without any oxytocin pretreatment

Also known as: pitocin

1.25mM Calcium-WITH oxytocin pretreatment; 2.5mM Calcium-WITH oxytocin pretreatment; 5.0mM Calcium-WITH oxytocin pretreatment

Calcium DRUG

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.

1.25mM Calcium-NO oxytocin pretreatment; 1.25mM Calcium-WITH oxytocin pretreatment; 2.5mM Calcium-NO oxytocin pretreatment; 2.5mM Calcium-WITH oxytocin pretreatment; 5.0mM Calcium-NO oxytocin pretreatment; 5.0mM Calcium-WITH oxytocin pretreatment

Eligibility Criteria

• Age: 16 Years - 40 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Samuel Lunenfeld Research Institute, Mount Sinai Hospital: lead

Study Sites (1)

Mount Sinai Hospital

Toronto, Ontario, M5G1X5, Canada

Location

MeSH Terms

Conditions

Postpartum Hemorrhage

Interventions

Oxytocin; Calcium

Condition Hierarchy (Ancestors)

Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Puerperal Disorders; Uterine Hemorrhage; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pituitary Hormones, Posterior; Pituitary Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins; Metals, Alkaline Earth; Elements; Inorganic Chemicals; Metals; Blood Coagulation Factors; Biological Factors

Study Officials

• Mrinalini Balki, MD

  MOUNT SINAI HOSPITAL

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 9, 2014
• First Posted: October 24, 2014
• Study Start: November 1, 2014
• Primary Completion: March 1, 2015
• Study Completion: March 1, 2015
• Last Updated: May 27, 2015

Record last verified: 2015-05

Locations

CA (1)