Clinical Safety Study of Human Embryonic Stem Cell Derived Mesenchymal Cells in the Treatment of Moderate and Severe Intrauterine Adhesions

Phase 1

• Conditions: Intrauterine Adhesion
• Interventions: Biological: Inject stem cells; Biological: Inject a solution of stem cell preparation

• Registration Number: NCT04232592
• Lead Sponsor: Qi Zhou

Brief Summary

To observe the clinical safety of intrauterine injection of human embryonic stem cell derived mesenchymal cells in the treatment of moderate and severe intrauterine adhesion, and to preliminarily explore its clinical effectiveness in promoting endometrial regeneration and repair.

Detailed Description

In this study, a single-center, controlled, open-label design was used for a dose escalation study.To observe the clinical safety of intrauterine injection of human embryonic stem cell derived mesenchymal cells in the treatment of moderate and severe intrauterine adhesion, and to preliminarily explore its clinical effectiveness in promoting endometrial regeneration and repair.

Study Timeline

• Status Verified: 2019-12
• Study First Submitted: 2019-12-27
• Study Start: 2020-01
• Study First Submitted QC: 2020-01-15
• Last Update Submitted: 2020-01-15
• Study First Posted: 2020-01-18
• Last Update Posted: 2020-01-18
• Primary Completion: 2022-01
• Study Completion: 2022-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: Female
• Target Recruitment: 32

Inclusion Criteria

• 18 ≤ age ≤38, female;
• According to the 1988 American Fertility Society (AFS) diagnostic criteria, patients with uterine adhesions diagnosed with full civil capacity and with a score of ≥5 were enrolled in the study;
• The patient had one or more of the following clinical symptoms: reduced menstruation or amenorrhea, periodic abdominal pain, secondary infertility, recurrent abortion, premature delivery and other adverse pregnancy outcomes;
• The uterus was smaller than 8 weeks gestation and the uterine cavity depth was less than 12 cm;
• The second to fifth day of menstruation FSH <10mIU/mL, AMH >1.2ng/mL, AFC>6;
• Understand and sign informed consent voluntarily.

Exclusion Criteria

• Patients with acute pelvic inflammation or endometriosis;
• Having or having a history of malignancy;
• Thrombus, lupus erythematosus and other hormone use contraindications; Allergic to albumin products;
• Patients with uterine malformation, adenomyosis, submucosal uterine fibroids,and uterine fibroids of any site >5cm;
• Patients who were using anticoagulants or who had not recovered normal platelet function 10 days after discontinuation of antiplatelet drugs;
• Previous history of abnormal coagulation function or abnormality before cell transplantation;
• Always has a history of abnormal bleeding (such as abnormal bleeding during tooth extraction), or their immediate family members have hemorrhagic disease,such as hemophilia, bleeding symptoms (e.g., hematemesis, black, serious or recurrent nasal bleeding, coughing up blood, obvious hematuria, gastrointestinal bleeding, or intracranial hemorrhage), or suspected of vascular malformation such as aneurysm by researchers determine influence cell implant operation;
• Alcohol or drug addiction;
• Participated in other interventional clinical trials within 90 days before the informed consent was signed or before the cell transplantation;
• Had used glucocorticoids or immunosuppressive drugs within 12 weeks before signing the informed consent;
• Had used antipsychotic drugs, such as antidepressants and anti-manic drugs, within 12 weeks before signing the informed consent;
• Severe heart failure within 24 weeks before the informed consent;
• Glomerular filtration rate (eGFR) <90ml/min;
• ALT>3 times normal upper limit;
• Concomitant with other serious systemic diseases, such as pulmonary heart disease, severe chronic obstructive pulmonary disease (COPD), etc;
• Patients with severe clinical infection should receive antibiotics within 1 week before signing the informed consent;
• Active infectious diseases, including but not limited to positive human immunodeficiency virus and syphilis antibody;
• The researchers considered poor compliance;
• Other conditions not suitable for participation in this clinical trial.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Injected stem cell group	Inject stem cells	The stem cells will injected.
Stem cell preparation solution injection group	Inject a solution of stem cell preparation	The solution of stem cells preparation will be injected.

Primary Outcome Measures

Name	Time	Method
Incidence of different Adverse Events of transplantation of mesenchymal cells from human embryonic stem cells	Within 48 weeks after surgery	Adverse events (AE), severe adverse events (SAE), and treatment-related adverse events (TEAE) occurred within 48 weeks after surgery.

Secondary Outcome Measures

Name	Time	Method
Menstrual volume change	12 months	Menstrual volume change will be assessed according to menstrual blood loss chart.
The endometrial biopsies for Ki67	12 months	Ki67 expression levels during the two endometrial biopsies will be measured.
Normal recovery rate of endometrial thickness	12 months	Normal recovery rate of endometrial thickness at 1 and 2 months after surgery will be measured (effective rate = endometrium \> 6mm after surgery/all participants ×100%).
Intrauterine adhesions score	12 months	Intrauterine adhesions score will be measured according to the American Fertility Society in 1988 diagnostic criteria for intrauterine adhesions.The scores range from 1 to 12. Higher scores mean a worse outcome.
The endometrial biopsies for CD31	12 months	Immunohistochemical results of CD31 during the two endometrial biopsies will be measured.
The endometrial biopsies for estrogen	12 months	Estrogen receptor levels during the two endometrial biopsies will be measured.
recurrence rate of intrauterine adhesions	12 months	Recurrence rate of intrauterine adhesions (defined as patients with recurrence of intrauterine adhesions reviewed by hysteroscopy at 1 month/total patients ×100%) will be measured.
Clinical pregnancy rate	12 months	Clinical pregnancy rate, abortion rate, live birth rate, and sustained pregnancy rate (defined as live pregnancy over 12 weeks) will be assessed.