Clinical trial NCT01954095: The Impact of Vaginal and IM Progestins on the Cervix
Official title: Determining the Pharmacodynamic Impact of Vaginal and IM Progestins on the Cervix
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Preterm Birth
Short Cervical Length
Keywords: 17-OHPC, Prometrium, Cerclage, Pre-term birth, Short cervix
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
Collaborators: name: Indiana University
name: University of Texas
name: University of Washington
name: RTI International
First posted: 2013-10-01
Enrollment: 89
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: This study consists of 4 groups of women who are between 16 0/7 - 23 6/7 weeks gestation. The allocation of a subject to a group is based on two objective assessments (history of preterm birth and cervical length) and the joint clinical decision of the woman and her physician regarding treatment options.

Study participants who have no prior preterm births and a normal cervical length will be assigned to Group 1. If the participant has no prior preterm births and a short cervical length, she will be assigned to Group 2 regardless of treatment or no treatment. Group assignment for women with a prior preterm birth and normal cervical length is based on 17-OHPC use. Participants who elect to use 17-OHPC will be assigned to Group 3 and those who choose not to receive any treatment will be assigned to Group 4.

Brief summary: The purpose of this study is to analyze how the body handles and responds to progesterone treatment in parous and nulliparous women at risk of pre-term birth.

Detailed description: 17-hydroxyprogesterone caproate (17-OHPC) has recently been shown to reduce the rate of recurrent preterm birth while intravaginal progesterone has been shown to reduce the rate of preterm birth in women with short cervix. While these interventions have reduced the rate of preterm birth, the mechanisms of action of these medications are unknown. The objective of this study is to collect and analyze blood and cervicovaginal fluids from pregnant women receiving these medications or other interventions such as cerclage, pessary, NSAIDs, and combinations thereof. The goal of the analyses is to assess the impact of these interventions on the cervical proteome, cervical cytokines and cervical structure and to identify potential biomarkers of response and non-response thus providing insights into the mechanisms of action of these drugs.

Eligibility criteria: Inclusion Criteria

All Groups

* Singleton gestation (16 0/7 - 23 6/7 weeks gestation)
* Willing to provide informed consent
* Age 18 - 50 years inclusive

Additionally,

Group 1: One or more prior term births (\>37 0/7 weeks); No prior spontaneous birth at 16 0/7 - 36 6/7 weeks; and normal cervical length (\>25 mm)

Group 2: Cervical length of 20 mm or less at 16 0/7 - 23 6/7 weeks

Groups 3 and 4: History of prior spontaneous birth at 16 0/7 - 34 0/7 weeks and normal cervical length (\> 25mm) at enrollment.

Exclusion Criteria

All Groups

* Active labor
* Active bleeding
* On progestin therapy, chronic steroid, or current NSAID therapy
* Actively receiving study treatment in another clinical trial (observational trials allowed)
* Major fetal malformation lethal anomalies, or anomalies that may lead to early delivery or increased risk of neonatal death e.g., gastroschisis, spina bifida, or serious karyotypic abnormalities
* Amniotic membranes prolapsed beyond the external os (ostium of uterus) or protruding into the vagina
* Pregnancy without a viable fetus
* Prenatal care or delivery planned elsewhere (unless the study visits can be made as scheduled and complete outcome information can be obtained)

Additionally:

Group 1: Cervical dilation greater than or equal to 3cm

Group 2: Prior preterm birth (16 0/7 - 34 0/7); active deep vein thrombosis, pulmonary embolism, or history of these conditions; known liver dysfunction or disease (active hepatitis, HIV)

Group 3: inability or unwillingness to use a 17-OHPC compounded product similar in composition to the FDA-approved product; allergy to 17-OHPC or its components

Groups 1, 3, and 4: cerclage in place or anticipated; congenital mullerian abnormality of the uterus; positive for bacterial vaginosis, chlamydia, gonorrhea, or trichomonas

Groups 3 and 4: current or history of thrombosis or thromboembolic disorders; known or suspected breast cancer, other hormone-sensitive cancer, or history of these conditions; undiagnosed abnormal vaginal bleeding unrelated to pregnancy; cholestatic jaundice of pregnancy, liver tumors, benign or malignant, or active liver disease; uncontrolled hypertension

Primary outcomes:
measure: Biomarkers
timeFrame: 2 Weeks
Secondary outcomes:
measure: Cervical sonographic changes
timeFrame: 8 Weeks
measure: Protein Expression
timeFrame: 8 Weeks
measure: Cervical cytokines
timeFrame: 8 Weeks
measure: Individual cytokines
timeFrame: 8 Weeks
measure: Cervical MMPs
timeFrame: 8 Weeks
measure: Single nucleotide polymorphisms
timeFrame: 8 Weeks
measure: Biomarkers
timeFrame: 8 Weeks
Other outcomes:
Locations:
city: Indianapolis
country: United States
facility: Indiana University School of Medicine
state: Indiana
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: Galveston
country: United States
facility: University of Texas Medical Branch
state: Texas
city: Seattle
country: United States
facility: University of Washington
state: Washington
Study officials:
affiliation: University of Washington
name: Mary F Hebert, PharmD, FCCP
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Pittsburgh
name: Steve Caritis, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Texas
name: Gary Hankins, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Indiana University School of Medicine
name: David Flockhart, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: