A prospective, pharmacokinetic study of active drug levels and steroid hormone profiles in women treated with vaginal progesterone therapy

Study ID
STU 072016-069

Cancer Related
No

Healthy Volunteers
Yes

Study Sites

  • Parkland Health & Hospital System
  • UT Southwestern-Other

Contact
Lisa Moseley
214/648-2591
LISA.MOSELEY@UTSouthwestern.edu

Principal Investigator
Sarah Happe, M.D.

Summary

We will take a subgroup of women identified as being at risk for recurrent spontaneous preterm birth who are initiating vaginal progesterone therapy. We will obtain daily blood samples at initiation of therapy and a various points later in gestation to audit the pharmacologic properties of this therapy. We will use a micronized progesterone 90mg vaginal gel (Crinone 8% vaginal gel) administered daily as standard of care. analysis will be conducted by sampling serum and plasma from these women, and the specimens will be stored for analysis at a later time. a consent for use of biological specimens will be completed for all enrolled study patients. The first interval for blood sampling will be at initiation of therapy between 16-20 completed weeks of gestation (period #1), and they will have one-10mL tube of blood drawn daily for a total of 8 consecutive days. The patients will see a provider in the clinic prior to having blood drawn at the first and the last visits (visits #1 and #8) of this period as standard of care. all other visits (visits #2x7) will be nurse-only visits for blood draws, and all participants will be compensated $100 for each completed nurse-only visit they attend during this period. additionally, participants will have daily consecutive blood draws between 27-28 completed weeks of gestation (period #2), 30-31 completed weeks of gestation (period #3), and 33-34 completed weeks gestation (period #4). at each of these later intervals, participants will have one-10mL tube of blood drawn daily for 5 consecutive days. Women will be compensated $100 for each blood draw completed a during these three time periods.
Following consent and acquisition of samples, all specimens will be processed and stored (-80 degrees Celsius) for batch-run analysis. analysis of these samples will include study of serum and plasma levels of progesterone as well as a panel of other steroid hormones (Progesterone; 17-hydroxyprogesterone; Cortisol; Cortisone; 11-deoxycortisol; Corticosterone; 11-deoxycorticosterone rostenedione; Testosterone; aldosterone; estradiol; estrone; DHea Sulfate; 18-hydroxycorticosterone; 21-deoxycortisol; Dihydrotestosterone rosterone; 5a-androstanediol; Pregnenolone; 17-hydroxypregnenolone; Dehydroepiandrosterone; 5-androstenediol). These analytes will be quantitatively measured using HPLC-MS (high performance liquid chromatography-mass spectrometry with either aPCi (atmospheric pressure chemical ionization), or eSi (electrospray ionization). GC-MS (gas chromatography-mass spectrometry) may also be utilized if required. all of these analyses will be conducted by one of the co-investigators (Jeffrey McDonald).
in addition to these quantitative analyte levels, we will review the clinical outcomes of pregnancy-that is, preterm birth. To ascertain information from these pregnancies, we will review prior medical records of delivery information and query the obstetric database maintained by the obstetrics/Maternal Fetal Medicine Department. This database is maintained for operations, including quality assurance, and is able to be accessed only by the epidemiologist within the obstetrics Department (Don Mcintire, listed). The database uses a secure file server that is password protected and encrypted. We will query this database for all pertinent deliveries and excluding women as defined (see below). all identifiers will be removed and replaced with a non-identifiable code. The key to the coding system will be located in an electronic file that is password protected and encrypted and able to be accessed only by the epidemiologist listed. Following publication, the key to the coding system will be destroyed by purging the file so that there is no direct or indirect link to subject identifiers or other information. Calculations for statistical analysis will be conducted with Dr. Don Mcintire and the Department of obstetrics statistical services department.

Participant Eligibility

Women will be included in this study if they meet the following criteria:
1) Are of adult reproductive age (between the ages of 18 and 49 years old)
2) Are pregnant with a singleton gestation
3) Have a history of a prior spontaneous preterm due to preterm rupture of membranes or preterm labor
4) Are receiving vaginal progesterone therapy