The Placental Secretome as a Therapeutic Tool to Prevent Inflammation-induced Preterm Birth (PLACENTOMICS)

March 17, 2025 updated by: Fondazione Policlinico Universitario Agostino Gemelli IRCCS

The Placenta-derived Secretome of Mesenchymal Stromal Cells as a Therapeutic Tool to Prevent Inflammation-induced Preterm Birth

Preterm birth complicates 10% of all pregnancies and is the leading cause of perinatal morbidity and mortality worldwide. Intra-amniotic inflammation (IAI) and chorioamnionitis are well-established causes of PTB; however, a treatable infectious trigger is identified in only 50% of cases.In sterile IAI and/or preterm premature rupture of membranes (pPROM), there are currently no effective therapeutic options to reduce inflammation, promote amniotic sac healing, and prevent preterm birth. Growing evidence suggests that the secretome of mesenchymal stem cells (MSC) exhibits immunomodulatory and tissue-regenerative properties, making it a promising therapeutic tool for inflammatory disorders. Specifically, the conditioned medium from human amniotic mesenchymal stromal cells (CM-hAMSC) has been successfully used to treat various preclinical inflammatory disease models.

The aims of this study will be:1) to evaluate the activation of the NLRP3 inflammasome in hAM cells and peripheral blood mononuclear cells (PBMCs) from women with PTB. 2)To investigate the effect of CM-hAMSC on NLRP3 activation induced by lipopolysaccharide (LPS) and nigericin in cultured human amniotic epithelial cells (hAECs), amniotic mesenchymal stromal cells (hAMSCs), and PBMCs.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

Preterm birth complicates 10% of all pregnancies and is the leading cause of perinatal morbidity and mortality worldwide. Among all PTB cases, 70% occur spontaneously (SPTB), while the remaining 30% are medically indicated due to severe intrauterine growth restriction (IUGR). Intra-amniotic inflammation (IAI) and chorioamnionitis are well-established causes of SPTB; however, a treatable infectious trigger is identified in only 50% of cases.In sterile IAI and/or preterm premature rupture of membranes (pPROM), there are currently no effective therapeutic options to reduce inflammation, promote amniotic sac healing, and prevent preterm birth.Recent studies have identified the activation of the NLRP3 inflammasome in human amniotic membranes (hAM) as a key mechanism in the pathogenesis of SPTB. Targeting NLRP3 as a therapeutic approach for inflammatory diseases is rapidly advancing. Growing evidence suggests that the secretome of mesenchymal stem cells (MSC) exhibits immunomodulatory and tissue-regenerative properties, making it a promising therapeutic tool for inflammatory disorders. Specifically, the conditioned medium from human amniotic mesenchymal stromal cells (CM-hAMSC) has been successfully used to treat various preclinical inflammatory disease models.

The aims of this study will be:1) to evaluate the activation of the NLRP3 inflammasome in hAM cells and peripheral blood mononuclear cells (PBMCs) from women with PTB. 2)To investigate the effect of CM-hAMSC on NLRP3 activation induced by lipopolysaccharide (LPS) and nigericin in cultured human amniotic epithelial cells (hAECs), amniotic mesenchymal stromal cells (hAMSCs), and PBMCs.

Study Type

Interventional

Enrollment (Estimated)

60

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
    • Lazio
      • Roma, Lazio, Italy, 00168
        • Fondazione Policlinico Universitario A. Gemelli IRCCS, UOC Ostetricia e Patologia Ostetrica

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • Full-term uncomplicated pregnancy, without any medical conditions or ongoing pharmacological treatment (control group).
  • Pregnancy complicated by spontaneous preterm birth (gestational age 24-32 weeks).
  • Pregnancy complicated by medically indicated preterm birth (gestational age 24-32 weeks).

Exclusion Criteria:

  • Age <18 years
  • Chronic infections (HIV or HCV)
  • Cancer
  • Multiple pregnancy
  • Inability to provide informed consent

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Women with spontaneous preterm birth
Women enrolled in this study will undergo a venous blood draw (3 mL) via venipuncture from the antecubital fossa at the time of delivery. The placenta and amniochorionic membranes (hAM) will be collected within 30 minutes after delivery, performed via cesarean section. Additionally, a 3 mL sample of umbilical cord blood will be drawn from the residual cord attached to the placenta immediately after clamping.
Other: Venous blood sampling
Venous blood sampling (3 mL) via venipuncture from the antecubital fossa at the time of delivery
Other: Tissues sampling
Sampling of the placenta and amniochorionic membranes (hAM) at delivery
Other: Umbilical cord blood sampling
Umbilical cord blood sampling from the residual cord attached to the placenta immediately after clamping.
Active Comparator: Women with medically induced preterm birth
Women enrolled in this study will undergo a venous blood draw (3 mL) via venipuncture from the antecubital fossa at the time of delivery. The placenta and amniochorionic membranes (hAM) will be collected within 30 minutes after delivery, performed via cesarean section. Additionally, a 3 mL sample of umbilical cord blood will be drawn from the residual cord attached to the placenta immediately after clamping.
Other: Venous blood sampling
Venous blood sampling (3 mL) via venipuncture from the antecubital fossa at the time of delivery
Other: Tissues sampling
Sampling of the placenta and amniochorionic membranes (hAM) at delivery
Other: Umbilical cord blood sampling
Umbilical cord blood sampling from the residual cord attached to the placenta immediately after clamping.
Active Comparator: Healthy women with at least two previous uncomplicated pregnancies
Women enrolled in this study will undergo a venous blood draw (3 mL) via venipuncture from the antecubital fossa at the time of delivery. The placenta and amniochorionic membranes (hAM) will be collected within 30 minutes after delivery, performed via cesarean section. Additionally, a 3 mL sample of umbilical cord blood will be drawn from the residual cord attached to the placenta immediately after clamping.
Other: Venous blood sampling
Venous blood sampling (3 mL) via venipuncture from the antecubital fossa at the time of delivery
Other: Tissues sampling
Sampling of the placenta and amniochorionic membranes (hAM) at delivery
Other: Umbilical cord blood sampling
Umbilical cord blood sampling from the residual cord attached to the placenta immediately after clamping.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Anti-inflammatory effects of conditioned medium
Time Frame: Through study completion, an average of 1 year
To investigate the effect of CM-hAMSC on NLRP3 activation induced by lipopolysaccharide (LPS) and nigericin in cultured hAECs, hAMSCs, and PBMCs
Through study completion, an average of 1 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Inflammasome activation
Time Frame: Through study completion, an average of 1 year
To assess NLRP3 inflammasome activation in hAM cells and peripheral blood mononuclear cells (PBMCs) from women with term or preterm birth, whether spontaneous or medically indicated.
Through study completion, an average of 1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Investigators

  • Principal Investigator: Chiara Tersigni, MD, Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 11, 2025

Primary Completion (Estimated)

March 20, 2026

Study Completion (Estimated)

March 20, 2028

Study Registration Dates

First Submitted

March 11, 2025

First Submitted That Met QC Criteria

March 17, 2025

First Posted (Actual)

March 25, 2025

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

March 17, 2025

Last Verified

March 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 7273

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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