The Effect of Sulfasalazine on CRH Levels in Pregnant Women

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

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.

Study Overview

• Status: Recruiting
• Conditions: Preterm Birth
• Intervention / Treatment: Drug: Sulfasalazine

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Vanessa Martinez, MPH; Phone Number: 2017379179; Email: vm310@rwjms.rutgers.edu
• Study Contact Backup: Name: Emily Rosenfeld, DO; Phone Number: 7324024960; Email: er720@rwjms.rutgers.edu

Study Locations

• United States
  • New Jersey
    • New Brunswick, New Jersey, United States, 08901
      • Recruiting
      • Rutgers Robert Wood Johnson Medical School
      • Contact: Jessica Fields, MD; Phone Number: 732-235-6632; Email: jf993@rwjms.rutgers.edu
      • Contact: Shama Khan, MS; Phone Number: 732-235-6632; Email: khansp@rwjms.rutgers.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sulfasalazine; 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; Sulfasalazine will be administered between 24 and 36 weeks of pregnancy
No Intervention: Standard Care; Pregnant persons will receive standard care in pregnancy.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Rutgers, The State University of New Jersey
• Investigators: Principal Investigator: Emily Rosenfeld, DO, Rutgers Robert Wood Johnson Medical School

Publications and helpful links

General Publications

• McLean M, Bisits A, Davies J, Woods R, Lowry P, Smith R. A placental clock controlling the length of human pregnancy. Nat Med. 1995 May;1(5):460-3. doi: 10.1038/nm0595-460.
• Wang B, Parobchak N, Rosen T. RelB/NF-kappaB2 regulates corticotropin-releasing hormone in the human placenta. Mol Endocrinol. 2012 Aug;26(8):1356-69. doi: 10.1210/me.2012-1035. Epub 2012 Jun 25.
• Wang B, Parobchak N, Martin A, Rosen M, Yu LJ, Nguyen M, Gololobova K, Rosen T. Screening a small molecule library to identify inhibitors of NF-kappaB inducing kinase and pro-labor genes in human placenta. Sci Rep. 2018 Jan 26;8(1):1657. doi: 10.1038/s41598-018-20147-0.
• Norgard B, Fonager K, Pedersen L, Jacobsen BA, Sorensen HT. Birth outcome in women exposed to 5-aminosalicylic acid during pregnancy: a Danish cohort study. Gut. 2003 Feb;52(2):243-7. doi: 10.1136/gut.52.2.243.
• Mogadam M, Dobbins WO 3rd, Korelitz BI, Ahmed SW. Pregnancy in inflammatory bowel disease: effect of sulfasalazine and corticosteroids on fetal outcome. Gastroenterology. 1981 Jan;80(1):72-6.
• Hensleigh PA, Kauffman RE. Maternal absorption and placental transfer of sulfasalazine. Am J Obstet Gynecol. 1977 Feb 15;127(4):443-4. doi: 10.1016/0002-9378(77)90510-5. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2023
• Primary Completion (Estimated): January 31, 2026
• Study Completion (Estimated): June 30, 2026

Study Registration Dates

• First Submitted: January 17, 2023
• First Submitted That Met QC Criteria: January 26, 2023
• First Posted (Actual): January 30, 2023

Study Record Updates

• Last Update Posted (Actual): September 22, 2025
• Last Update Submitted That Met QC Criteria: September 17, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: randomized controlled trial; preterm birth; sulfasalazine; corticotropin releasing hormone
• Additional Relevant MeSH Terms: Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Premature Birth; Sulfur Compounds; Organic Chemicals; Amides; Sulfonamides; Sulfones; Sulfasalazine
• Other Study ID Numbers: Pro2021001951

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Deidentified data will be provided to those inquire to the corresponding author of the manuscript if published. If no manuscript is published, inquiries can be directed to the principal investigator of the study.
• IPD Sharing Time Frame: Data will be available on publication and remain available for two years.
• IPD Sharing Access Criteria: The principal investigator will individually assess all requests for data.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No