Safety and Efficacy of Umbilical Cord Mesenchymal Stem Cell Local Intramuscular Injection for Treatment of Uterine Scars

Study Overview
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Brief Summary
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This is a single center, randomized, double blind, placebo controlled study to evaluate the safety and efficacy of umbilical cord mesenchymal stem cell local intramuscular injection for treatment of caesarean section uterine scars.

Detailed Description
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In recent decades, the percentage of Cesarean section (CS) deliveries has dramatically increased around the world. While it allows safe delivery in many situations, the risks of severe maternal complications associated with cesarean delivery are higher than those associated with vaginal delivery. These maternal complications include short term, long-term, the next pregnancy, and the non-pregnant state, such as abnormal uterine bleeding and postmenstrual spotting. Uterine niche, also named cesarean scar defect, deficient cesarean scar, pouch, or diverticulum, is defined as a triangular anechoic structure at the site of the scar or a gap in the myometrium at the site of a previous caesarean section. It is one of the most common complications associated with previous cesarean section. The primary clinical manifestation is postmenstrual spotting, which may seriously affect the daily life of patients. The treatment includes medical treatment, such as oral contraceptives, and surgical methods, such as hysteroscopy resectoscopic correction, endometrial ablation, laparoscopic surgery, and transvaginal repair surgery. Although good outcomes are reported in each study, present treatments could not decrease the incidence among women after undergoing cesarean section. Mesenchymal stem cells (MSCs) are long-lived cells with the ability of both self-renewal and differentiation into multi-potential cells, such as osteoblasts, adipocytes and smooth muscle cells. Trials with MSCs in patients after myocardial infarction have shown an excellent safety and efficacy. In this trial, the investigators postulate that MSCs can reduce uterine niche and convert scar tissue to viable myometrium. To test the hypothesis, the investigators therefore undertake a Phase II clinical trial of the treatment for uterine niche among primiparous women who undergo cesarean section. This is a randomized, double-blind, placebo-controlled clinical trial designed to investigate the efficacy and safety of umbilical cord mesenchymal stem cells treatment on the caesarean section uterine scars. A total of one hundred and twenty (120) participants will be randomized (1:1) to receive direct local intramuscular injection of 1*10^7 MSCs (a dose of 1*10^7 cells in 1 ml of 0.9% saline) (MSCs group) or an identical-appearing 1ml of 0.9% saline placebo (placebo-controlled group). Cesarean procedures and care will follow usual practices. All participants will be performed by obstetricians from the investigators' department using a unified double-layer uterine closure technique with a continuous absorbable polyglycolic 1-0 suture. After suturing the uterine incision, direct local intramuscular injection will be performed in the uterine incision as soon as possible on the operating table. One ml solution will be injected as twenty aliquots of 0.05ml into each injection site on the incision. Injection sites will be selected near the incision at evenly 20 different sites. Participants will be followed up at 6 weeks, 3 months and 6 months. For the purpose of the endpoint analysis and safety evaluations, the investigators will utilize an intention-to-treat study population.

Official Title
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A Phase II, Randomized, Double-Blind, Placebo-Controlled Study of the Safety and Efficacy of Umbilical Cord Mesenchymal Stem Cell Local Intramuscular Injection for Treatment of Uterine Scars

Conditions
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Uterine Scar

Intervention / Treatment
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* Other: Umbilical cord MSCs
* Other: 0.9% Saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Primiparous women receiving cesarean delivery Ages between 21-35 years Gestation ages ≥ 37 weeks and < 42 weeks Willing to comply with study dosing and completed the entire course of the study Willing to give and sign an informed consent form and a photographic release form Exclusion Criteria: Fibroids Placenta previa Placenta abruption Multiple gestation Antepartum hemorrhage Preeclampsia/Eclampsia Hepatic or renal dysfunction Any systemic uncontrolled disease Inability to provide consent

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Umbilical cord MSCs Group<br>1*10^7 Umbilical cord MSCs | Other: Umbilical cord MSCs<br>* Participants will receive direct local intramuscular injection of 1*10^7 MSCs (in 1ml of 0.9% saline) in the uterine incision.<br>|
| Placebo Comparator: Placebo-Controlled Group<br>1ml of 0.9% saline | Other: 0.9% Saline<br>* Participants will receive direct local intramuscular injection 1ml of 0.9% saline in the uterine incision.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with uterine niche | The niche is defined as a triangular anechoic area at the presumed site of incision in the uterus by transvaginal utrasonography. | 6 months post treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of uterine scar thickness | The scar thickness be measured using a transvaginal utrasonography | 6 weeks, 3 and 6 months post treatment | 
| Change of uterine scar area | The scar area will be measured using a transvaginal utrasonography | 6 weeks, 3 and 6 months post treatment | 
| Number of participants with endometritis | Endometritis is defined as the presence of at least two of the following signs with no other recognized cause: fever (temperature of at least 38℃), abdominal pain, uterine tenderness, or purulent drainage from the uterus. | 6 months post treatment | 
| Number of participants with wound infection | Wound infection is defined as the presence of either superficial or deep incisional surgical-site infection characterized by cellulitis or erythema and induration around the incision or purulent discharge from the incision site with or without fever and included necrotizing fasciitis. | 6 months post treatment | 
| Immunoglobulin concentrations in breast milk and serum | Breast milk and serum immunoglobulin (IgG, IgA, IgM) and the complement (C3, C4) are detected by transmission immune turbidity method using automatic biochemical analyzer. | 6 weeks, 3 and 6 months post treatment | 
| Adverse events occurrence | Adverse events will be evaluated since the baseline visit until 6 months after the end of the treatment. | 6 months post treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mesenchymal Stem Cells, Cesarean Section, Uterine Scar