Clinical trial NCT05703425: The Effect of Sulfasalazine on CRH Levels in Pregnant Women
Official title: The Effect of Sulfasalazine on CRH Levels in Pregnant Women With a History of Pre-Term Birth: A Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Preterm Birth
Keywords: preterm birth
sulfasalazine
corticotropin releasing hormone
randomized controlled trial
Lead sponsor: Rutgers, The State University of New Jersey
Sponsor class: OTHER
First posted: 2023-01-30
Enrollment: 50
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Serum CRH levels
timeFrame: between 28 and 36 weeks of pregnancy
Secondary outcomes:
measure: Spontaneous preterm birth < 37 weeks gestation
timeFrame: up to 37 weeks of pregnancy
measure: Spontaneous preterm birth < 34 weeks gestation
timeFrame: up to 34 weeks of pregnancy
measure: Medically indicated preterm birth < 37 weeks gestation
timeFrame: up to 37 weeks of pregnancy
measure: Digital cervical exam at 36 weeks gestational age
timeFrame: between 35 weeks and 36 weeks 6 days of pregnancy
measure: Composite neonatal morbidity
timeFrame: From birth of the neonate until 28 days of life
Other outcomes:
Locations:
city: New Brunswick
country: United States
facility: Rutgers Robert Wood Johnson Medical School
state: New Jersey
Study officials:
affiliation: Rutgers Robert Wood Johnson Medical School
name: Todd Rosen, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.