Uterine Electrical Activity Before and After Progesterone Treatment for Preterm Labor

Uterine Abdominal Electromyography Measurements Before and After Progesterone Treatments for Preterm Labor

This study will examine the effects of various formulations of progesterone on uterine electromyographic (EMG) activity in pregnant patients in premature labor to determine if progesterone will suppress uterine electrical activity and which formulation may be best for inhibition of uterine activity. Patients will be monitored prior to treatment and following treatment (every 2 to 4 hours) with one of three different formulations of progesterone for up to two days. Patients will continue to be observed until they deliver. Comparisons will be for uterine EMG activity from before treatment to that following treatments at 2, 4, 8, 12 24 and 48 hours and times of delivery after treatments (hours or days following treatments). Comparisons between mean values for EMG activity between the various treatments at the various times will also be made.

Study Overview

• Status: Withdrawn
• Conditions: Preterm Labor
• Intervention / Treatment: Drug: Experimental: Vaginal progesterone; Drug: Experimental: Topical progesterone; Drug: Experimental: Intramuscular progesterone

Detailed Description

In this study the investigators will compare the effects of vaginal progesterone, intramuscular applied progesterone and topical progesterone on uterine electromyographic activity (EMG)in patients in preterm labor. Electrodes will be placed on the abdominal surface of pregnant patients in preterm labor and the EMG activity recorded for 30 minutes before and following treatments for up to 48 hours. In addition data on delivery times will be recorded when patients delivery vaginally or by Cesarian section. Eligibility criteria: Healthy patients without infection or rupture of membranes with gestational ages between 24 to 34 weeks. Outcome measures: Comparisons of uterine EMG activity (EMG amplitude, frequency, and specific information on EMG bursts) from measurements before treatment to following treatments with progesterone preparations at various times (at 2,4,8, 12,24 and to 48 hours following treatment) and delivery times of patients on various treatments (hours or days following treatments, average delivery times in patients treated by various formulations). Comparisons of mean values in uterine EMG activity (EMG amplitude, burst frequency and frequency of signals in a burst, power spectrum analysis of the bursts and peak power density spectrum of bursts) from before treatment to following treatments at 2 to 24 hours will be compared. Also the time of delivery following treatments will be obtained and the average time of delivery following the various treatments compared.

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85013
      • St. Joseph's Hospital and Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 17 years to 40 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Healthy patients in preterm labor between 24 to 34 weeks of gestation presenting to St. Joseph's Hospital and Medical Center.
• Preterm labor is defined as at least 6 contractions in 60 minutes with a cervix either dilated to 2 centimeters or effaced to 80% and a cervical length measured by ultrasound of less than 3 centimeters, and a positive fetal fibronectin.
• Maternal ages will be within 17 to 40 year-old range.

Exclusion Criteria:

• Patients with preterm premature rupture of membranes (PPROM) will be excluded from the study, due to possibility of ascending infection, as will those patients with suspected chorioamnionitis.
• Patients with medical conditions that contraindicate tocolysis, such as non-reassuring fetal heart tracings, will also be excluded.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Vaginal progesterone; vaginal 150 mg micronized progesterone cream delivered via a vaginal applicator; dosed daily (Prochieve, Columbia Laboratories)	Drug: Experimental: Vaginal progesterone; Vaginal progesterone formulation (150 mg micronized progesterone daily); Other Names: Prochieve, Columbia Laboratories
Experimental: Topical progesterone; topical 150 mg micronized progesterone gel applied to abdomen via a novel applicator; dosed daily	Drug: Experimental: Topical progesterone; Progesterone will be applied daily (150 mg micronized progesterone)by topical application; Other Names: No other name available
Experimental: Intramuscular progesterone; injected IM (upper arm or thigh via syringe) 50mg/day micronized progesterone (Watson Pharmaceuticals)	Drug: Experimental: Intramuscular progesterone; Preterm labor patients will be injected IM with micronized progesterone (50 mg/day).; Other Names: Watson Laboratories

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Inhibition of uterine electromyographic (EMG) activity by various formulations of progesterone.	Uterine electrical activity will be recorded (for 30 minutes at each time point) from the abdominal surface of pregnant patients before (30 minutes before treatment) and following treatment (at 2, 4, 8, 12, 24 and up to 48 hours) with either vehicles or progesterone treatments to evaluate if the treatments reduce EMG activity and therefore may be potential candidates for possible interventions for treating a preterm labor.	EMG will be measured at various times including 0 time pretreatment and up to 48 hours after treatments

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effects of progesterone on uterine EMG activity and preterm birth	Secondary measures: Patients will be followed (up to 16 weeks) until delivery by vaginal or Cesarian section to see if any intervention (progesterone treatment) affects timing of birth.	Various times after treatments up to 16 weeks to determine when the patients deliver

Collaborators and Investigators

• Sponsor: St. Joseph's Hospital and Medical Center, Phoenix
• Investigators: Principal Investigator: James Balducci, MD, St. Joseph's Hospital and Medical Center, Phoenix; Principal Investigator: Robert Garfield, PhD, St. Joseph's Hospital and Medical Center, Phoenix

Publications and helpful links

General Publications

• Hassan SS, Romero R, Vidyadhari D, Fusey S, Baxter JK, Khandelwal M, Vijayaraghavan J, Trivedi Y, Soma-Pillay P, Sambarey P, Dayal A, Potapov V, O'Brien J, Astakhov V, Yuzko O, Kinzler W, Dattel B, Sehdev H, Mazheika L, Manchulenko D, Gervasi MT, Sullivan L, Conde-Agudelo A, Phillips JA, Creasy GW; PREGNANT Trial. Vaginal progesterone reduces the rate of preterm birth in women with a sonographic short cervix: a multicenter, randomized, double-blind, placebo-controlled trial. Ultrasound Obstet Gynecol. 2011 Jul;38(1):18-31. doi: 10.1002/uog.9017. Epub 2011 Jun 15.
• Kuon RJ, Shi SQ, Maul H, Sohn C, Balducci J, Maner WL, Garfield RE. Pharmacologic actions of progestins to inhibit cervical ripening and prevent delivery depend on their properties, the route of administration, and the vehicle. Am J Obstet Gynecol. 2010 May;202(5):455.e1-9. doi: 10.1016/j.ajog.2010.03.025.
• Lucovnik M, Kuon RJ, Chambliss LR, Maner WL, Shi SQ, Shi L, Balducci J, Garfield RE. Use of uterine electromyography to diagnose term and preterm labor. Acta Obstet Gynecol Scand. 2011 Feb;90(2):150-7. doi: 10.1111/j.1600-0412.2010.01031.x. Epub 2010 Dec 7.
• Kuon RJ, Shi SQ, Maul H, Sohn C, Balducci J, Shi L, Garfield RE. A novel optical method to assess cervical changes during pregnancy and use to evaluate the effects of progestins on term and preterm labor. Am J Obstet Gynecol. 2011 Jul;205(1):82.e15-20. doi: 10.1016/j.ajog.2011.02.048. Epub 2011 Feb 23.
• Ruddock NK, Shi SQ, Jain S, Moore G, Hankins GD, Romero R, Garfield RE. Progesterone, but not 17-alpha-hydroxyprogesterone caproate, inhibits human myometrial contractions. Am J Obstet Gynecol. 2008 Oct;199(4):391.e1-7. doi: 10.1016/j.ajog.2008.06.085.

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2011
• Primary Completion (Actual): October 1, 2013
• Study Completion (Actual): October 1, 2013

Study Registration Dates

• First Submitted: March 31, 2011
• First Submitted That Met QC Criteria: July 28, 2011
• First Posted (Estimate): August 1, 2011

Study Record Updates

• Last Update Posted (Actual): October 26, 2022
• Last Update Submitted That Met QC Criteria: October 24, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: Premature birth; Progesterone; Preterm labor; Progestins; Uterine contractility; Uterine electromyography
• Additional Relevant MeSH Terms: Pregnancy Complications; Obstetric Labor Complications; Premature Birth; Obstetric Labor, Premature; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Progestins; Progesterone
• Other Study ID Numbers: IRB#10OB059