The Effect of Sulfasalazine on CRH Levels in Pregnant Women

Study Overview
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Brief Summary
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The goal of this randomized clinical trial is to assess sulfasalazine as a potential treatment to prevent recurrent preterm birth. The main questions it aims to answer are: Does sulfasalazine down regulate corticotropin releasing hormone (CRH) levels in pregnant persons with a prior history of preterm birth? Does sulfasalazine reduce the incidence of recurrent preterm birth in pregnant persons given drug vs. controls? Consenting participants will be randomized to receive sulfasalazine or to a control group and will undergo serial blood draws to assess plasma CRH levels.

Detailed Description
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This is a study to assess the potential for sulfasalazine to prevent recurrent preterm birth. The investigators' main objective is to assess the effects of sulfasalazine on the maternal serum biomarker CRH, which is associated with preterm birth. The will be a pilot randomized controlled trial of pregnant multiparous patients who have had a prior preterm delivery. Pregnant women with a prior preterm birth are at high risk (about 20-30%) of having a recurrent preterm birth. The goal of the study will be to evaluate the effect of sulfasalazine on the maternal serum biomarker CRH at 28, 32, and 36 weeks gestation after randomization of patients to the study drug. Secondary objectives include evaluating the effect of sulfasalazine on the outcome of delivery less than 37 weeks gestation in this group of high risk pregnant women. Additional composite neonatal outcomes will be assessed. The proposed study has the potential to identify a novel, low-cost, orally available treatment for preterm delivery based on in vitro evidence and epidemiologic studies suggesting that sulfasalazine may be an effective intervention to prevent preterm birth. If the hypothesis put forth by the investigators is confirmed, sulfasalazine would be an attractive therapeutic intervention that could be implemented for the prevention of preterm birth in both developed and developing nations.

Official Title
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The Effect of Sulfasalazine on CRH Levels in Pregnant Women With a History of Pre-Term Birth: A Randomized Controlled Trial

Conditions
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Preterm Birth

Intervention / Treatment
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* Drug: Sulfasalazine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: > 18 years of age Singleton pregnancy Participants with a history of prior preterm birth in a previous pregnancy Participants must be between 12 and 22 weeks gestation. Participants must have their pregnancy dates confirmed by ultrasound. Exclusion Criteria: Participants < 18 years old Participants with a cervical length < 25 mm Participants with a multiple gestation Cerclage Progesterone administration Unwilling or unable to swallow the study agent capsule or consume an inert ingredient in the study agent capsule Acute liver disease or known liver abnormalities Other significant chronic medical or psychiatric illness that, in the investigator's opinion, would prevent participation in the study Known hypersensitivity to sulfasalazine Known glucose-6-phosphate dehydrogenase (G6PD) deficiency History of severe asthma Digoxin use Porphyria Intestinal obstruction Urinary tract obstruction Hepatic dysfunction Renal dysfunction Blood dyscrasia such as agranulocytosis, aplastic anemia.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sulfasalazine<br>Pregnant persons will receive sulfasalazine daily with 500 mg/daily and increasing by 500 mg/day every week until they reach a therapeutic dose of 1,000 mg twice daily. Drug will be started at 24 weeks estimated gestational age and ended at 36 weeks or earlier if preterm birth occurs. | Drug: Sulfasalazine<br>* Sulfasalazine will be administered between 24 and 36 weeks of pregnancy<br>|
| No Intervention: Standard Care<br>Pregnant persons will receive standard care in pregnancy. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum CRH levels | CRH will be assessed at 28, 32, and 36 weeks gestation | between 28 and 36 weeks of pregnancy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Spontaneous preterm birth < 37 weeks gestation | Preterm births prior to 37 weeks secondary to preterm labor (PTL) or premature Preterm births secondary to preterm labor or preterm rupture of the membranes (PPROM) | up to 37 weeks of pregnancy | 
| Spontaneous preterm birth < 34 weeks gestation | Preterm births prior to 34 weeks secondary to PTL or PPROM | up to 34 weeks of pregnancy | 
| Medically indicated preterm birth < 37 weeks gestation | Preterm births due to maternal or fetal disease not related to PTL or PPROM | up to 37 weeks of pregnancy | 
| Digital cervical exam at 36 weeks gestational age | Digital cervical exam at 36 weeks gestational age | between 35 weeks and 36 weeks 6 days of pregnancy | 
| Composite neonatal morbidity | Composite outcome including but not limited to Apgar neonatal death, respiratory distress, necrotizing enterocolitis, and bronchopulmonary dysplasia. | From birth of the neonate until 28 days of life | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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preterm birth, sulfasalazine, corticotropin releasing hormone, randomized controlled trial