The Impact of Vaginal and IM Progestins on the Cervix

Preterm Birth Clinical Trial

Official title:

Determining the Pharmacodynamic Impact of Vaginal and IM Progestins on the Cervix

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01954095
• Other study ID #: OPRU Progestin
• Status: Completed
• Phase: N/A
• First received: September 26, 2013
• Last updated: December 1, 2015
• Start date: August 2013
• Est. completion date: March 2015

Study information

• Verified date: December 2015
• Source: University of Pittsburgh
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review BoardUnited States: Federal Government
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 89
• Est. completion date: March 2015
• Est. primary completion date: January 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 50 Years

Eligibility

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

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Premature Birth
• Preterm Birth
• Short Cervical Length

Locations

Country	Name	City	State
United States	University of Texas Medical Branch	Galveston	Texas
United States	Indiana University School of Medicine	Indianapolis	Indiana
United States	University of Pittsburgh	Pittsburgh	Pennsylvania
United States	University of Washington	Seattle	Washington

Sponsors (5)

Lead Sponsor	Collaborator
University of Pittsburgh	Indiana University, RTI International, University of Texas, University of Washington

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Biomarkers	Proteins in the cervicovaginal fluid with expression changes two-fold or greater between day 0 and week 2 of either vaginal or IM progestin therapy.	2 Weeks	No
Secondary	Cervical sonographic changes	Changes in cervical sonographic gray scale density/length from weeks 0-2, 0-4, and 0-8 after the start of progestin therapy.	8 Weeks	No
Secondary	Protein Expression	Proteins in the cervicovaginal fluid whose expression changes significantly from weeks 0-4 and 0-8 after the start of progestin therapy.	8 Weeks	No
Secondary	Cervical cytokines	Changes in cervical cytokine inflammatory ratio weeks 0-2, 0-4, and 0-8 after the start of progestin therapy.	8 Weeks	No
Secondary	Individual cytokines	Changes in individual cytokines (IL-1a, IL-1ß, IL-1RA, IL-4, IL-6, IL-8, IL-10, IL-13, and TNF-a) from weeks 0-2, 0-4, and 0-8 after the start of progestin therapy.	8 Weeks	No
Secondary	Cervical MMPs	Changes in cervical MMPs 1, 2, 8 and 9 from weeks 0-2, 0-4, and 0-8 after the start of progestin therapy.	8 Weeks	No
Secondary	Single nucleotide polymorphisms	Test for association between single nucleotide polymorphisms (SNPs) in progestin and estrogen-related candidate genes and changes in the CVF proteome and cervical density and length.	8 Weeks	No
Secondary	Biomarkers	Proteins in the cervicovaginal fluid with expression changes two-fold or greater between weeks 0-4 and 0-8 of either vaginal or IM progestin therapy.	8 Weeks	No