PreeclampsiaPhase 1/2EXITPENCT07183384
MSC Exosome Therapy for Post-Preeclampsia Endothelial Dysfunction
A Phase 1/2 study testing Mesenchymal Stem Cell-Derived Exosomes in people with Preeclampsia and Postpartum, run by Universitas Padjadjaran at 1 site in Indonesia.
Trial summary
--- 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. Read more about this study
- Who is it for?
- Ages 18 to 50 years, women only
- Conditions the study is for
- Preeclampsia, Postpartum, Endothelial Injury
- What is being tested?
- Mesenchymal Stem Cell-Derived Exosomes
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 80 participants
- Where
- 1 siteIndonesia
- Study dates
- 1 Jul 2024to 1 Sep 2026
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- Postpartum
- Confirmed diagnosis of preeclampsia in the last pregnancy
- Postpartum period of first week and second week
- Able to provide informed consent
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Indonesia1 site, 1 recruiting
- Recruiting
Dr. Hasan Sadikin Central General Hospital
Bandung, West Java, 40161
Akhmad Y Pramatirta, M.D., Ph.D., +62 81320403090, akhmad.yogi@unpad.ac.id
Akhmad Y. Pramatirta, M.D., PhD
About this study
Official title: The Effectiveness of Mesenchymal Stem Cell-Derived Exosome Therapy in Improving Endothelial Dysfunction in Postpartum Mothers With a History of Preeclampsia
---
Why Is This Study Being Done?
Read more
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.
---
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).
---
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.
---
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.
Read the detailed description
---
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.
---
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%).
---
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.
---
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.
---
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)
---
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.
---
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.
---
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.
---
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
- Preeclampsia, Postpartum, Endothelial Injury, Exosome Multiomics, Cell Therapy
- Being tested
- Mesenchymal Stem Cell-Derived Exosomes, Placebo (Sterile Saline Solution)
- Keywords
- Preeclampsia, Postpartum, Stem Cell, Exosome, Cell Therapy
- Medical subject headings
- Pre-Eclampsia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Mesenchymal Stem Cell-Derived ExosomesBiological
Also called MSC-Exos, Fetal stem cell 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.
Placebo (Sterile Saline Solution)Other
Also called Normal saline, 0.9% sodium chloride
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.
| Study group | Role | What they receive |
|---|---|---|
| MSC-derived Exosome Therapy | Experimental | Participants receive Intravenous or Intramuscular MSC-derived exosomes. Receives: Biological: Mesenchymal Stem Cell-Derived Exosomes |
| Saline/Placebo | Placebo comparator | Participants receive Intravenous or Intramuscular sterile saline solution Receives: Other: Placebo (Sterile Saline Solution) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Endothelial Function Biomarker (miR-126-3p)
Measure: Change in miR-126-3p expression levels from baseline to 1 week post-intervention.
Method: RT-PCR analysis of blood samples. Unit: Fold change (relative expression). Scale Description: Continuous variable measured as fold change relative to baseline. Higher values indicate improved endothelial function. Normal range: 0.8-1.2 fold change. Values <0.8 indicate dysfunction.
Measured: Baseline and 1 week post-intervention
Secondary outcomes (17)
Systolic Blood Pressure
Measure: Change in systolic blood pressure from baseline. Unit: mmHg. Normal Range: 90-140 mmHg (postpartum). Values ≥140 mmHg indicate hypertension.
Measured: Baseline, first week, and 1 week post-intervention
Diastolic Blood Pressure
Measure: Change in diastolic blood pressure from baseline.
Unit: mmHg.
Normal Range: 60-90 mmHg (postpartum). Values ≥90 mmHg indicate hypertension.
Measured: Baseline, first week, and 1 week post-intervention
Hemoglobin Level
Measure: Change in hemoglobin concentration from baseline.
Unit: g/dL.
Normal Range: 11.0-15.0 g/dL (postpartum). Values <11.0 g/dL indicate anemia.
Measured: Baseline and 1 week post-intervention
Hematocrit Level
Measure: Change in hematocrit percentage from baseline.
Unit: Percentage (%).
Normal Range: 33-45% (postpartum). Values <33% indicate anemia.
Measured: Baseline and 1 week post-intervention
Leukocyte Count
Measure: Change in white blood cell count from baseline.
Unit: cells/μL.
Normal Range: 9,000-25,000 cells/μL (postpartum, elevated due to normal physiologic stress). Values >25,000 may indicate infection.
Measured: Baseline and 1 week post-intervention
Platelet Count
Measure: Change in platelet count from baseline.
Unit: cells/μL.
Normal Range: 150,000-400,000 cells/μL. Values <150,000 indicate thrombocytopenia.
Measured: Baseline and 1 week post-intervention
Mean Corpuscular Volume (MCV)
Measure: Change in mean corpuscular volume from baseline.
Unit: femtoliters (fL).
Normal Range: 80-100 fL. Values <80 fL indicate microcytic anemia; >100 fL indicate macrocytic anemia.
Measured: Baseline and 1 week post-intervention
Mean Corpuscular Hemoglobin Concentration (MCHC)
Measure: Change in mean corpuscular hemoglobin concentration from baseline.
Unit: g/dL.
Normal Range: 32-36 g/dL. Values <32 g/dL indicate hypochromic anemia.
Measured: Baseline and 1 week post-intervention
Proteinuria Level
Measure: Change in urine protein level from baseline using dipstick urinalysis.
Unit: Dipstick protein scale (qualitative).
Scale Description: Urine Dipstick Protein Scale:
Negative/Trace: Normal (no significant proteinuria)
- (30 mg/dL): Mild proteinuria
- (100 mg/dL): Moderate proteinuria
- (300 mg/dL): Severe proteinuria
- (>2000 mg/dL): Very severe proteinuria
Normal Range: Negative to Trace in postpartum period.
Interpretation: Higher grades indicate worse proteinuria. Grades 2+ and above indicate clinically significant proteinuria requiring monitoring.
Measured: Baseline and 1 week post-intervention
Uterine Artery Pulsatility Index (PI)
Measure: Change in Pulsatility Index of uterine artery measured by Doppler ultrasound.
Unit: Ratio (dimensionless).
Scale Description: Calculated as (peak systolic velocity - end diastolic velocity)/mean velocity. Normal postpartum range: 0.5-1.2. Higher values indicate increased vascular resistance.
Measured: Baseline and 1 week post-intervention
Uterine Artery Resistance Index (RI)
Measure: Change in Resistance Index of uterine artery measured by Doppler ultrasound.
Unit: Ratio (dimensionless).
Scale Description: Calculated as (peak systolic velocity - end diastolic velocity)/peak systolic velocity. Normal postpartum range: 0.4-0.8. Higher values indicate increased vascular resistance.
Measured: Baseline and 1 week post-intervention
Heart Rate
Measure: Change in heart rate from baseline.
Unit: beats per minute (bpm).
Normal Range: 60-100 bpm (postpartum may be slightly elevated 70-110 bpm). Values >110 bpm may indicate tachycardia.
Measured: Baseline, first week, and 1 week post-intervention
Respiratory Rate
Measure: Change in respiratory rate from baseline
Unit: breaths per minute
Normal Range: 12-20 breaths per minute. Values >20 may indicate tachypnea.
Measured: Baseline, first week, and 1 week post-intervention
Upper Extremity Edema Grade
Measure: Change in upper extremity edema grading from baseline.
Unit: Grade on standardized scale.
Scale Description: Postpartum Edema Grading Scale (0-4):
Grade 0: No edema
Grade 1: Mild pitting edema, barely perceptible
Grade 2: Moderate pitting edema, clearly visible
Grade 3: Severe pitting edema with obvious swelling
Grade 4: Very severe pitting edema with marked deformity.
Interpretation: Higher grades indicate worse edema. Grade 0-1 considered normal postpartum; Grades 2-4 indicate pathological edema.
Measured: Baseline and 1 week post-intervention
Lower Extremity Edema Grade
Measure: Change in lower extremity edema grading from baseline.
Unit: Grade on standardized scale.
Scale Description: Postpartum Edema Grading Scale (0-4) - same as above.
Interpretation: Higher grades indicate worse edema. Grade 0-1 considered normal postpartum; Grades 2-4 indicate pathological edema.
Measured: Baseline and 1 week post-intervention
Facial Edema Grade
Measure: Change in facial edema grading from baseline.
Unit: Grade on standardized scale.
Scale Description: Postpartum Edema Grading Scale (0-4) - same as above.
Interpretation: Higher grades indicate worse edema. Grade 0 considered normal postpartum; Grades 1-4 indicate pathological edema.
Measured: Baseline and 1 week post-intervention
Uterine Involution Status
Measure: Assessment of uterine involution progress measured by uterine height.
Unit: centimeters (cm) above symphysis pubis.
Normal Range:
Day 1 postpartum: At umbilicus (~12 cm)
Day 7 postpartum: 7-9 cm above symphysis pubis
Day 14 postpartum: 4-6 cm above symphysis pubis.
Interpretation: Expected decrease of ~1 cm per day. Slower decrease may indicate subinvolution.
Measured: Baseline and 1 week post-intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Sep 2025
- Study start1 Jul 2024
- Primary completion1 Jul 2026 (estimated)
- Study completion1 Sep 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for PreeclampsiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Universitas Padjadjaran
- Sponsor type
- University, hospital or other
- Collaborators
- Hasan Sadikin General Hospital, Dr Cipto Mangunkusumo General Hospital, Dr. Sardjito Hospital, Yogyakarta
- Responsible party
- Sponsor
- Investigators
- Akhmad Y Pramatirta, M.D., Ph.D, Principal investigator, Dr. Hasan Sadikin Central General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07183384
- Sponsor's protocol ID
- OBGY-202508.01
- Acronym
- EXITPE
- Status last verified
- Sep 2025
- First submitted
- 2 Sep 2025
- Last updated
- 19 Sep 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual participant data that underlie the results reported in publications from this study will be shared after de-identification, including biomarker data (miR-126-3p), clinical outcomes, safety parameters, and demographic data collected according to the study protocol. Sensitive information that could potentially re-identify participants will be excluded from shared datasets.
Publications
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.
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.
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.
PubMed 26032325
Study at a glance
From the registry record, last updated by the sponsor on 19 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effectiveness of Mesenchymal Stem Cell-Derived Exosome Therapy in Improving Endothelial Dysfunction in Postpartum Mothers With a History of Preeclampsia
- ClinicalTrials.gov ID
- NCT07183384
- Acronym / sponsor ID
- EXITPE / OBGY-202508.01
- Conditions
- Preeclampsia, Postpartum, Endothelial Injury, Exosome Multiomics, Cell Therapy
- Keywords
- Preeclampsia, Postpartum, Stem Cell, Exosome, Cell Therapy
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- Universitas PadjadjaranUniversity, hospital or other
- Collaborators
- Hasan Sadikin General Hospital, Dr Cipto Mangunkusumo General Hospital, Dr. Sardjito Hospital, Yogyakarta
- Study start
- 1 Jul 2024 (actual)
- Primary completion
- 1 Jul 2026 (estimated)
- Study completion
- 1 Sep 2026 (estimated)
- First posted
- 19 Sep 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
---
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.
---
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).
---
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.
---
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
---
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.
---
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%).
---
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.
---
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.
---
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)
---
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.
---
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.
---
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.
---
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| MSC-derived Exosome Therapy | Experimental | Biological: Mesenchymal Stem Cell-Derived ExosomesParticipants receive Intravenous or Intramuscular MSC-derived exosomes. |
| Saline/Placebo | Placebo comparator | Other: Placebo (Sterile Saline Solution)Participants receive Intravenous or Intramuscular sterile saline solution |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Postpartum
- Confirmed diagnosis of preeclampsia in the last pregnancy
- Postpartum period of first week and second week
- Able to provide informed consent
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Mesenchymal Stem Cell-Derived ExosomesAlso: MSC-Exos, Fetal stem cell exosomesMesenchymal 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. | Biological | MSC-derived Exosome Therapy |
| Placebo (Sterile Saline Solution)Also: Normal saline, 0.9% sodium chlorideSterile 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. | Other | Saline/Placebo |
Primary outcome
Change in Endothelial Function Biomarker (miR-126-3p)
Time frame: Baseline and 1 week post-intervention
Measure: Change in miR-126-3p expression levels from baseline to 1 week post-intervention. Method: RT-PCR analysis of blood samples. Unit: Fold change (relative expression). Scale Description: Continuous variable measured as fold change relative to baseline. Higher values indicate improved endothelial function. Normal range: 0.8-1.2 fold change. Values <0.8 indicate dysfunction.
17 secondary outcomes
Systolic Blood Pressure
Time frame: Baseline, first week, and 1 week post-intervention
Diastolic Blood Pressure
Time frame: Baseline, first week, and 1 week post-intervention
Hemoglobin Level
Time frame: Baseline and 1 week post-intervention
Hematocrit Level
Time frame: Baseline and 1 week post-intervention
Leukocyte Count
Time frame: Baseline and 1 week post-intervention
Platelet Count
Time frame: Baseline and 1 week post-intervention
Mean Corpuscular Volume (MCV)
Time frame: Baseline and 1 week post-intervention
Mean Corpuscular Hemoglobin Concentration (MCHC)
Time frame: Baseline and 1 week post-intervention
Proteinuria Level
Time frame: Baseline and 1 week post-intervention
Uterine Artery Pulsatility Index (PI)
Time frame: Baseline and 1 week post-intervention
Uterine Artery Resistance Index (RI)
Time frame: Baseline and 1 week post-intervention
Heart Rate
Time frame: Baseline, first week, and 1 week post-intervention
Respiratory Rate
Time frame: Baseline, first week, and 1 week post-intervention
Upper Extremity Edema Grade
Time frame: Baseline and 1 week post-intervention
Lower Extremity Edema Grade
Time frame: Baseline and 1 week post-intervention
Facial Edema Grade
Time frame: Baseline and 1 week post-intervention
Uterine Involution Status
Time frame: Baseline and 1 week post-intervention
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Sep 2025.
- BackgroundVioretti, 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.
- BackgroundGurnadi, 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.
- Background: PubMed 26032325Pramatirta 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.
- Individual participant dataSharing planned: Yes. Individual participant data that underlie the results reported in publications from this study will be shared after de-identification, including biomarker data (miR-126-3p), clinical outcomes, safety parameters, and demographic data collected according to the study protocol. Sensitive information that could potentially re-identify participants will be excluded from shared datasets.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Akhmad Y Pramatirta, M.D., Ph.D principal investigator
Dr. Hasan Sadikin Central General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Mesenchymal Stem Cell-Derived Exosomes in people with Preeclampsia and Postpartum, run by Universitas Padjadjaran at 1 site in Indonesia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 19 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Indonesia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Prima N Fauziah, S.Si., M.Si. (+62 85721368609, primanandafauziah@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Endothelial Function Biomarker (miR-126-3p) (time frame: Baseline and 1 week post-intervention). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07183384, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Sep 2025.