Progesterone for Pre-eclampsia
(PROGRESS Trial)
Recruiting in Palo Alto (17 mi)
Age: 18 - 65
Sex: Female
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Babbette Lamarca
Disqualifiers: Gestational age, Maternal compromise, Fetal compromise, others
No Placebo Group
Prior Safety Data
Approved in 3 Jurisdictions
Trial Summary
What is the purpose of this trial?The purpose of this study is to learn if giving 17-hydroxyprogesterone caproate (17 OHPC) to mothers with preeclampsia diagnosed before 34 weeks gestation improves mother and baby outcomes.
Do I need to stop my current medications for this trial?
The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.
What evidence supports the effectiveness of the drug 17-OHPC for treating preeclampsia?
Research shows that 17-OHPC can improve conditions related to preeclampsia, such as reducing high blood pressure and inflammation in pregnant rats. It also helps manage certain inflammatory markers in women with early-onset preeclampsia.
12345Is 17α-hydroxyprogesterone caproate generally safe for humans?
17α-hydroxyprogesterone caproate (17-OHPC) has been used since the 1950s for various conditions, but there are ongoing concerns about its safety, especially regarding long-term effects on children exposed in the womb. Additionally, the method of administration can pose risks like contamination and needlestick injuries.
12678How does the drug 17 OHPC differ from other treatments for pre-eclampsia?
17 OHPC is unique because it not only helps reduce high blood pressure in pre-eclampsia but also improves blood flow and reduces inflammation by increasing nitric oxide levels. Unlike other treatments, it also balances immune cells, which may help improve pregnancy outcomes.
123910Eligibility Criteria
This trial is for pregnant patients at UMMC with preterm preeclampsia between 23 and 34 weeks of gestation, who can consent to study procedures. It excludes those with conditions like PPROM after 34 weeks, low platelets, liver issues, severe fetal growth restriction, eclampsia, or any maternal/fetal condition requiring urgent delivery.Inclusion Criteria
UMMC antepartum patients with preterm PE between 23 0/7ths and 34 0/7ths weeks gestation when initially evaluated
Willing and able to understand study procedures and to provide informed consent
Exclusion Criteria
Gestational age >33 weeks or <23 weeks
Fetal compromise requiring emergent delivery (fetal bradycardia, recurrent late fetal heart rate decelerations, minimal to absent fetal heart rate variability)
Eclampsia
+12 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
1 week
1 visit (in-person)
Treatment
Participants receive 17 OHPC, 250mg IM at admission and every 7 days thereafter until delivery
Until delivery
Weekly visits for 17 OHPC administration
Monitoring
Blood samples collected at baseline, 24 hours after first dose, every 72 hours until delivery, and 24 hours after delivery
Until delivery
Multiple visits for blood sampling
Follow-up
Participants are monitored for safety and effectiveness after treatment
Until discharge
In-hospital monitoring until discharge
Participant Groups
The study investigates whether the hormone medication called 17-hydroxyprogesterone caproate (17 OHPC) can improve outcomes for mothers and babies when preeclampsia occurs before the baby is full-term.
2Treatment groups
Experimental Treatment
Active Control
Group I: ExperimentalExperimental Treatment1 Intervention
To determine if the addition of 17 OHPC to the management of Severe PE diagnosed prior to 34 weeks gestation improves maternal and perinatal outcomes.
Group II: ControlActive Control1 Intervention
To determine how close the molecular markers are with 17 OHPC added to the management protocol.
17 OHPC is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as Makena for:
- Prevention of preterm birth in high-risk pregnant individuals
- Advanced adenocarcinoma of the uterine corpus (Stage III or IV)
- Management of amenorrhea (primary and secondary) and abnormal uterine bleeding due to hormonal imbalance
🇪🇺 Approved in European Union as Proluton for:
- Habitual and imminent abortion
- Infertility due to corpus luteum insufficiency
- Primary and secondary amenorrhea
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Winfred L. Wiser HospitalJackson, MS
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Who Is Running the Clinical Trial?
Babbette LamarcaLead Sponsor
References
17-hydroxyprogesterone caproate significantly improves clinical characteristics of preeclampsia in the reduced uterine perfusion pressure rat model. [2021]Preeclampsia is characterized by increased uterine artery resistance index, chronic immune activation, and decreased circulating nitric oxide levels. 17-α-Hydroxyprogesterone caproate (17-OHPC) is a synthetic metabolite of progesterone used for the prevention of recurrent preterm birth. We hypothesized that 17-OHPC could reduce mean arterial pressure by decreasing inflammation, whereas improving vasodilation by increasing nitric oxide bioavailability and uterine artery resistance index during late gestation in the reduced uterine perfusion pressure (RUPP) rat model of preeclampsia. 17-OHPC (3.32 mg/kg) was intraperitoneally administered on gestation day 18 into RUPP rats, carotid catheters inserted, and mean arterial pressure, blood, and tissues were collected on day 19. Mean arterial pressure in normal pregnant (NP; n=13) was 92±2.0 and increased to123±2.0 in RUPP (n=18; P
Population pharmacokinetics of 17α-hydroxyprogesterone caproate in singleton gestation. [2021]17α-hydroxyprogesterone caproate (17-OHPC) reduces the rate of preterm birth in women with a prior preterm birth. Limited data exist on the pharmacokinetics (PK) of 17-OHPC or the plasma concentrations achieved during therapy. In this study, we evaluated the population PK of 17-OHPC in pregnant subjects with singleton gestation and also evaluated intrinsic and extrinsic factors that may potentially affect 17-OHPC PK in this patient population.
17-Hydroxyprogesterone caproate improves hypertension and renal endothelin-1 in response to sFlt-1 induced hypertension in pregnant rats. [2023]Preeclampsia (PE) is characterized by new onset hypertension in association with elevated soluble fms-like tyrosine kinase-1 (sFlt-1) and preproendothelin-1 (PPET-1) levels. Currently there is no effective treatment for PE except for early delivery of the fetal placental unit, making PE a leading cause for premature births worldwide. Administration of 17-hydroxyprogesterone caproate (17-OHPC) is used for prevention of recurrent preterm birth. This study was designed to test the hypothesis that 17-OHPC improves hypertension and ET-1 in response to elevated sFlt-1 in pregnant rats. sFlt-1 was infused into normal pregnant (NP) Sprague-Dawley rats (3.7 μg·kg-1·day-1 for 6 days, gestation days 13-19) in the presence or absence of 17-OHPC (3.32 mg/kg) administered via intraperitoneal injection on gestational days 15 and 18. Mean arterial blood pressure (MAP), pup and placenta weights, renal cortex PPET-1 mRNA levels and nitrate-nitrite levels were measured on GD 19. Infusion of sFlt-1 into NP rats elevated mean arterial pressure (MAP) compared with control NP rats: 115 ± 1 (n = 13) vs. 99 ± 2 mmHg (n = 12, p < 0.05). 17-OHPC attenuated this hypertension reducing MAP to 102 ± 3 mmHg in sFlt-1 treated pregnant rats (n = 8). Neither pup nor placental weight was affected by sFlt-1 or 17-OHPC. Importantly, renal cortex PPET-1 mRNA levels were elevated 3 fold in NP + sFlt-1 rats compare to NP rats, which decreased with 17-OHPC administration. Plasma nitrate-nitrite levels were 44 ± 9 µM in NP rats (n = 9), 20 ± 3 µM in NP + sFlt-1 (n = 7), which increased to 42 ± 11 µM NP + sFlt-1 + 17OHPC (n = 6). Administration of 17-OHPC improves clinical characteristics of preeclampsia in response to elevated sFlt-1 during pregnancy.
Development and validation of a high-performance liquid chromatography-mass spectrometric assay for the determination of 17alpha-hydroxyprogesterone caproate (17-OHPC) in human plasma. [2019]A sensitive and specific method for the determination of 17alpha-hydroxyprogesterone caproate (17-OHPC) in human plasma using high-performance liquid chromatography and mass spectrometry has been developed and validated. Plasma samples were processed by a solid phase extraction (SPE) procedure using Oasis HLB extraction cartridge prior to chromatography. Medroxyprogesterone acetate (MPA) was used as the internal standard. Chromatography was performed using Waters C18 Symmetry analytical column, 3.5 microm, 2.1 mm x 10 mm, using a gradient elusion with a mobile phase consisting of acetonitrile [A] and 5% acetonitrile in water [B], with 0.1% formic acid being added to both [A] and [B], at a flow rate 0.2 ml/min. The retention times of 17-OHPC and MPA were 8.1 and 5.0 min, respectively, with a total run time of 15 min. Analysis was performed on Thermo Electron Finnigan TSQ Quantum Ultra mass spectrometer in a selected reaction-monitoring (SRM), positive mode using electron spray ionization (ESI) as an interface. Positive ions were measured using extracted ion chromatogram mode. The extracted ions following SRM transitions monitored were m/z 429.2-->313.13 and 429.2-->271.1, for 17-OHPC and m/z 385.1-->276 for MPA. The extraction recoveries at concentrations of 5, 10 and 50 ng/ml were 97.1, 92.6 and 88.7%, respectively. The assay was linear over the range 0.5-50 ng/ml for 17-OHPC. The analysis of standard samples for 17-OHPC 0.5, 1, 2.5, 5, 10, 25 and 50 ng/ml demonstrated a relative standard deviation of 16.7, 12.4, 13.7, 1.4, 5.2, 3.7 and 5.3%, respectively (n=6). This method is simple, adaptable to routine application, and allows easy and accurate measurement of 17-OHPC in human plasma.
Effect of 17-Hydroxyprogesterone Caproate on Interleukin-6 and Tumor necrosis factor-alpha in expectantly managed early-onset preeclampsia. [2023]The study aimed to evaluate the effect of 17 hydroxy progesterone (17-OHPC) on interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in expectantly managed early-onset preeclampsia (PE). A randomized open-label controlled study included women who were diagnosed as early-onset PE if they assigned to expectant management according to the American College of Obstetricians and Gynecologists (ACOG) 2013 criteria for diagnosis of severity of PE. Patients were randomized into Group A (40 patients) received 17-OHPC 250 mg intra-muscular at admission and every 7 days thereafter and Group B (40 patients) was given the usual conservative measures of early-onset PE as a control group. Blood samples were obtained from all participants for measurements of TNF-α and IL-6 levels at admission and repeated at termination of pregnancy. The primary outcome was the mean difference between TNF-α and IL-6 levels before and after treatment in both groups. TNF-α and IL-6 levels at admission were not different between the two groups. However, there was a significant difference concerning these inflammatory biomarkers within the same group at admission and at termination (p
In utero exposure to 17α-hydroxyprogesterone caproate and risk of cancer in offspring. [2023]17α-hydroxyprogesterone caproate is a synthetic progestogen initially approved in the 1950s to treat gynecologic and obstetrical conditions. Despite continued concerns about safety and short-term efficacy regarding the use of 17α-hydroxyprogesterone caproate for the prevention of preterm birth in pregnant women, little is known about the long-term effects of 17α-hydroxyprogesterone caproate on the health of the offsprings.
Development and usability of a new subcutaneous auto-injector device to administer hydroxyprogesterone caproate to reduce the risk of recurrent preterm birth. [2022]Current administration of hydroxyprogesterone caproate (HPC) by intramuscular injection is associated with limitations, including the potential for human error and contamination, patient anxiety, and increased risk of needlestick injury.
Qualitative and quantitative measures of various compounded formulations of 17-alpha hydroxyprogesterone caproate. [2021]17-alpha hydroxyprogesterone caproate (17-OHPC) is available both as an Food and Drug Administration (FDA)-approved medication and as a product prepared for individual patients by compounding pharmacies. Compounding pharmacies may omit the preservative that is used in the FDA-approved formulation or use an alternate preservative and may dispense 17-OHPC in containers that differ from the FDA-approved product. The objective of this study was to assess the stability and the microbiologic and pyrogen status of 17-OHPC formulations under various compounding and dispensing conditions.
Progesterone blunts vascular endothelial cell secretion of endothelin-1 in response to placental ischemia. [2021]Preeclampsia (PE) is associated with hypertension and elevated endothelin (ET-1), an indicator of endothelial cell activation and dysfunction. Reduction of uteroplacental perfusion (RUPP) in the pregnant rat model of PE is characterized by elevated mean arterial pressure, inflammatory cytokines, and activation of the ET-1 system. We aim to determine whether 17-alpha-hydroxyprogesterone caproate (17-OHPC) or progesterone suppresses these pathways.
17-Hydroxyprogesterone caproate improves T cells and NK cells in response to placental ischemia; new mechanisms of action for an old drug. [2021]Preeclampsia (PE) is new onset hypertension during pregnancy associated with increased uterine artery resistance (UARI) and an imbalance among CD4 + T lymphocytes and natural killer (NK) cells. We have shown an important role for 17-hydroxyprogesterone caproate (17-OHPC) to improve hypertension and fetal demise in the RUPP rat model of PE. However we have not examined a role for 17-OHPC to improve NK cells and CD4+TH2 cells as possible mechanisms for improved fetal weight and hypertension. Therefore, we hypothesized that 17-OHPC lowers NK cells while improving the T cell ratio in the RUPP rat. RUPP was surgically induced on gestational day 14 in pregnant rats. 17-OHPC (3.32 mg/kg) was administered intraperitoneal on day 15, UARI was measured on day 18. Blood pressure (MAP), blood and tissues were collected on GD 19. MAP in NP rats (n = 9) was 100 ± 2, 104 ± 6 in Sham rats (n = 8), 128 ± 2 in RUPP (n = 11) and 115 ± 3 mmHg in RUPP + 17-OHPC (n = 10), p < 0.05. Pup weight and UARI were improved after 17-OHPC. Total and cytolytic placental NK cells were 38 ± 5, and 12 ± 2% gate in RUPP rats which decreased to 1.6 ± 0.5 and 0.4 ± 0.2% gate in RUPP + 17OHPC rats. CD4+ T cells were 40 ± 3 in RUPP rats, which significantly decreased to 7 ± 1 RUPP + 17-OHPC rats. Circulating and placental TH2 cells were 6.0 ± 1, 0.3 ± 0.1% gate in RUPP rats and 12 ± 1%, 2 ± 0.5% gate in RUPP + 17-OHPC rats, p < 0.05 This study identifies new mechanisms whereby 17-OHPC improves outcomes in response to placental ischemia.