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

Phase 2
Withdrawn
Conditions
Uterine Scar
Interventions
Other: Umbilical cord MSCs
Other: 0.9% Saline
Registration Number
NCT02968459
Lead Sponsor
Maternal and Child Health Hospital of Foshan
Brief Summary

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

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.

Recruitment & Eligibility

Status
WITHDRAWN
Sex
Female
Target Recruitment
Not specified
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Umbilical cord MSCs GroupUmbilical cord MSCs1\*10\^7 Umbilical cord MSCs
Placebo-Controlled Group0.9% Saline1ml of 0.9% saline
Primary Outcome Measures
NameTimeMethod
Number of participants with uterine niche6 months post treatment

The niche is defined as a triangular anechoic area at the presumed site of incision in the uterus by transvaginal utrasonography.

Secondary Outcome Measures
NameTimeMethod
Number of participants with endometritis6 months post treatment

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.

Number of participants with wound infection6 months post treatment

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.

Change of uterine scar area6 weeks, 3 and 6 months post treatment

The scar area will be measured using a transvaginal utrasonography

Change of uterine scar thickness6 weeks, 3 and 6 months post treatment

The scar thickness be measured using a transvaginal utrasonography

Immunoglobulin concentrations in breast milk and serum6 weeks, 3 and 6 months post treatment

Breast milk and serum immunoglobulin (IgG, IgA, IgM) and the complement (C3, C4) are detected by transmission immune turbidity method using automatic biochemical analyzer.

Adverse events occurrence6 months post treatment

Adverse events will be evaluated since the baseline visit until 6 months after the end of the treatment.

Trial Locations

Locations (1)

Maternal and Child Health Hospital of Foshan

🇨🇳

Foshan, Guangdong, China

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