Clinical trial NCT02968459: Safety and Efficacy of Umbilical Cord Mesenchymal Stem Cell Local Intramuscular Injection for Treatment of Uterine Scars
Official title: 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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Uterine Scar
Keywords: Mesenchymal Stem Cells
Cesarean Section
Uterine Scar
Lead sponsor: Maternal and Child Health Hospital of Foshan
Sponsor class: OTHER
First posted: 2016-11-18
Enrollment: 0
Sex: FEMALE
Minimum age (years): 21
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of participants with uterine niche
timeFrame: 6 months post treatment
Secondary outcomes:
measure: Change of uterine scar thickness
timeFrame: 6 weeks, 3 and 6 months post treatment
measure: Change of uterine scar area
timeFrame: 6 weeks, 3 and 6 months post treatment
measure: Number of participants with endometritis
timeFrame: 6 months post treatment
measure: Number of participants with wound infection
timeFrame: 6 months post treatment
measure: Immunoglobulin concentrations in breast milk and serum
timeFrame: 6 weeks, 3 and 6 months post treatment
measure: Adverse events occurrence
timeFrame: 6 months post treatment
Other outcomes:
Locations:
city: Foshan
country: China
facility: Maternal and Child Health Hospital of Foshan
state: Guangdong
Study officials:
affiliation: Maternal and Child Health Hospital of Foshan
name: Zhengping Liu, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Fan D, Wu S, Ye S, Wang W, Guo X, Liu Z. Umbilical cord mesenchyme stem cell local intramuscular injection for treatment of uterine niche: Protocol for a prospective, randomized, double-blinded, placebo-controlled clinical trial. Medicine (Baltimore). 2017 Nov;96(44):e8480. doi: 10.1097/MD.0000000000008480.