MSC Exosome Therapy for Post-Preeclampsia Endothelial Dysfunction

NCT ID: NCT07183384

Last Updated: 2025-09-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

80 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-07-01

Study Completion Date

2026-09-01

Brief Summary

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Why Is This Study Being Done?

Women who have preeclampsia during pregnancy face a much higher risk of heart disease later in life. Preeclampsia is a serious pregnancy condition that causes high blood pressure and damages blood vessels. Even after the baby is born, the blood vessels do not fully heal on their own, which can lead to heart problems/cardiovascular years later.

This study tests whether a new treatment called exosomes can help repair damaged blood vessels in women who had preeclampsia. Exosomes are tiny particles that come from stem cells and contain healing substances that may help blood vessels work better.

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What Will Happen in This Study?

This study will include 80 women who recently gave birth and had preeclampsia during their pregnancy. Half of the women will receive the exosome treatment through an IV, and half will receive a placebo (a substance with no active treatment).

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What Will Participants Need to Do?

Participants will:

* Have blood tests and other health checks
* Receive one treatment through an IV
* Return for follow-up visits at 1 week after treatment
* Have tests to check how well their blood vessels are working

Who Can Join This Study?

Women who:

* Recently gave birth (within 1-2 weeks)
* Had preeclampsia during their last pregnancy
* Are healthy enough to participate
* Can give permission to join the study

What Are the Possible Benefits and Risks?

The treatment may help repair blood vessel damage and reduce the risk of future heart disease. The exosome treatment appears to be safe based on other studies, but like any medical treatment, there may be side effects.

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How Long Will the Study Last?

The main treatment happens during one visit, with follow-up visits for 1 week to check on participants' health and see if the treatment is working.

This research may lead to new ways to protect women's heart health after pregnancy complications.

Detailed Description

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Background and Rationale

Preeclampsia affects 3-5% of pregnancies globally and represents a severe pregnancy-specific syndrome characterized by widespread maternal endothelial dysfunction. The pathophysiology involves abnormal trophoblast invasion leading to placental ischemia. Beyond immediate perinatal risks, preeclampsia carries devastating long-term cardiovascular consequences, with women experiencing a four-fold increased risk of heart failure, a 2.5-fold increased risk of coronary heart disease, and a two-fold increased risk of stroke and cardiovascular death. Moreover, post-cesarean postpartum mothers with a history of preeclampsia face particularly elevated risks, with cesarean delivery increasing postpartum preeclampsia risk by two- to seven-fold compared to vaginal delivery. This increased risk stems from altered hemodynamics, surgical stress responses, and compromised vascular integrity following cesarean procedures.

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Scientific Innovation

This study represents a paradigm shift from symptomatic management to active regenerative therapy using mesenchymal stem cell-derived exosomes (MSC-Exos). MSC-Exos offer several advantages over traditional approaches: natural tropism for vascular tissues, multi-pathway targeting capabilities, reduced immunogenicity compared to cell-based therapies, and superior circulation stability. Recent systematic reviews demonstrate favorable safety profiles with a low incidence of serious adverse events (0.7%).

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Intervention Details

Participants will receive a single intravenous or intramuscular dose of MSC-derived exosomes obtained from fetal adipose stem cells (ASC), produced under Good Manufacturing Practice (GMP) conditions. The exosomes contain bioactive cargo including growth factors, cytokines, proteins, and therapeutic microRNAs (particularly miR-126-3p) that mediate intercellular communication and tissue repair. Control participants will receive sterile saline solution of identical volume via the same route.

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Biomarker Strategy

The study employs miR-126-3p as the primary biomarker based on its exceptional diagnostic performance for endothelial dysfunction. miR-126-3p demonstrates high sensitivity (85.71%) and specificity (81.82%) with an area under the curve (AUC) of 0.792 for detecting endothelial dysfunction. This microRNA serves dual roles as both a pathological mediator and therapeutic target, making it ideal for monitoring treatment response. miR-126-3p is significantly downregulated in preeclampsia and directly regulates key angiogenic pathways including PI3K/AKT and MAPK/ERK signaling.

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Mechanistic Rationale

MSC-derived exosomes promote endothelial repair through multiple complementary mechanisms:

* Anti-inflammatory effects by promoting M2 macrophage polarization and reducing pro-inflammatory cytokines (IL-1β, IL-6, TNF-α).
* Angiogenic promotion through delivery of pro-angiogenic factors including VEGF, VEGFR-2, and specific microRNAs.
* Anti-apoptotic activity protecting endothelial cells via regulation of Bcl-2/Bax/Caspase-3 pathways.
* Vascular barrier protection by maintaining intercellular junctions and preventing vascular permeability.

Clinical Assessment Protocol

The study incorporates comprehensive clinical monitoring including Hematology examination (Hemoglobin, MCV \& MCHC, Hematocrit, Leukocyte, Platelets), Vital Signs Assessment (Blood Pressure, Respiratory Rate, Heart Rate), Edema assessment (Upper Extremity Edema, Lower Extremity Edema, Facial Edema), proteinuria evaluation, and Imaging Outcome (Pulsatility Index (PI), and Resistance Index (RI) Uterine Artery, Uterine Involusion)

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Therapeutic Window and Follow-Up

The intervention targets the critical postpartum period (first-second week) when endothelial regeneration naturally occurs but may be compromised in preeclampsia patients. The 24-month follow-up period aligns with evidence suggesting therapeutic interventions during early postpartum may help reset long-term cardiovascular risk trajectories. This extended monitoring allows assessment of sustained therapeutic effects and long-term cardiovascular protection.

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Statistical Considerations

Sample size calculation (n=40 per group) is based on power analysis with α=0.05 and 80% power, accounting for a 10% dropout rate. The study design incorporates interim analysis at 50% recruitment with predetermined safety stopping rules monitored by an independent Data Safety Monitoring Board.

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Expected Clinical Impact

This study could establish a new therapeutic paradigm for postpartum care, shifting from reactive symptomatic management to proactive regenerative intervention. Success would provide the foundation for developing standardized exosome therapy protocols, potentially reducing long-term cardiovascular disease burden in high-risk postpartum populations, and contributing to improved maternal health outcomes with significant economic implications for healthcare systems.

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Regulatory and Safety Framework

The study operates under comprehensive ethical oversight with approval from the institutional Health Research Ethics Committee. Safety monitoring includes comprehensive adverse event reporting protocols and predefined safety stopping criteria to ensure participant protection throughout the study duration.

Conditions

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Preeclampsia Postpartum Endothelial Injury Exosome Multiomics Cell Therapy

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Randomized, placebo-controlled clinical trial with parallel group design. Participants will be randomized 1:1 to receive either MSC-derived exosomes or placebo (sterile saline solution). Both groups will be followed for the same duration with identical assessment schedules.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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MSC-derived Exosome Therapy

Participants receive Intravenous or Intramuscular MSC-derived exosomes.

Group Type EXPERIMENTAL

Mesenchymal Stem Cell-Derived Exosomes

Intervention Type BIOLOGICAL

Mesenchymal stem cell-derived exosomes isolated from adipose-derived stem cells (ASC). The exosomes contain bioactive molecules including microRNAs (particularly miR-126-3p), proteins, and lipids that promote endothelial repair and regeneration. The product is manufactured under GMP conditions and administered as a single Intravenous or Intramuscular infusion.

Saline/Placebo

Participants receive Intravenous or Intramuscular sterile saline solution

Group Type PLACEBO_COMPARATOR

Placebo (Sterile Saline Solution)

Intervention Type OTHER

Sterile saline solution (0.9% sodium chloride) administered Intravenous or Intramuscular as placebo control. The volume and administration method are identical to the active treatment to maintain blinding.

Interventions

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Mesenchymal Stem Cell-Derived Exosomes

Mesenchymal stem cell-derived exosomes isolated from adipose-derived stem cells (ASC). The exosomes contain bioactive molecules including microRNAs (particularly miR-126-3p), proteins, and lipids that promote endothelial repair and regeneration. The product is manufactured under GMP conditions and administered as a single Intravenous or Intramuscular infusion.

Intervention Type BIOLOGICAL

Placebo (Sterile Saline Solution)

Sterile saline solution (0.9% sodium chloride) administered Intravenous or Intramuscular as placebo control. The volume and administration method are identical to the active treatment to maintain blinding.

Intervention Type OTHER

Other Intervention Names

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MSC-Exos Fetal stem cell exosomes Normal saline 0.9% sodium chloride

Eligibility Criteria

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Inclusion Criteria

* Postpartum
* Confirmed diagnosis of preeclampsia in the last pregnancy
* Postpartum period of first week and second week
* Able to provide informed consent

Exclusion Criteria

* History of chronic hypertension prior to pregnancy
* Major cardiovascular disease history
* Active systemic infection
* Endothelial Injury history
* Active smoking status including vape, alcohol, drug addiction.
Minimum Eligible Age

18 Years

Maximum Eligible Age

50 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Dr. Hasan Sadikin General Hospital, Bandung, Indonesia

UNKNOWN

Sponsor Role collaborator

Dr Cipto Mangunkusumo General Hospital

OTHER

Sponsor Role collaborator

Dr. Sardjito Hospital, Yogyakarta

UNKNOWN

Sponsor Role collaborator

Universitas Padjadjaran

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Akhmad Y Pramatirta, M.D., Ph.D

Role: PRINCIPAL_INVESTIGATOR

Dr. Hasan Sadikin Central General Hospital

Locations

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Dr. Hasan Sadikin Central General Hospital

Bandung, West Java, Indonesia

Site Status RECRUITING

Countries

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Indonesia

Central Contacts

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Prima N Fauziah, S.Si., M.Si.

Role: CONTACT

+62 85721368609

Nurul Azizah, S.Tr.Keb.

Role: CONTACT

+62 81312971480

Facility Contacts

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Akhmad Y Pramatirta, M.D., Ph.D.

Role: primary

+62 81320403090

References

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Vioretti, R., Khairani, A. F., Fauziah, P. N., & Hilmanto, D. (2018). An evaluation of soyghurt potential on tumor necrosis factor-α and soluble endoglin levels in preclampsia maternal serum-induced placental trophoblast cell in vitro. International Food Research Journal, 25(4), 1397-1402.

Reference Type BACKGROUND

Gurnadi, J. I., Mose, J. C., Handono, B., Fauziah, P. N., & Pramatirta, A. Y. (2015). Correlation between fms-Like tyrosine kinase-1 (sFlt-1) cell-free messenger RNA expression and fms-Like tyrosine kinase-1 (sFlt-1) protein level in severe preeclampsia and normal pregnancy. International Journal of Integrated Health Sciences, 3(2), 66-71.

Reference Type BACKGROUND

Pramatirta AY, Mose J, Effendi JS, Krisnadi SR, Anwar AD, Fauziah PN, Gurnadi JI, Rihibiha DD. Correlation between cell-free mRNA expressions and PLGF protein level in severe preeclampsia. BMC Res Notes. 2015 Jun 2;8:208. doi: 10.1186/s13104-015-1186-9.

Reference Type BACKGROUND
PMID: 26032325 (View on PubMed)

Other Identifiers

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OBGY-202508.01

Identifier Type: -

Identifier Source: org_study_id

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