Human Amniotic Epithelial Stem Cell in Treatment of Refractory Severe Intrauterine Adhesion

This project will investigate the safety and effectiveness of human amniotic epithelial stem cells for treatment of severe refractory Asherman's syndrome.

Study Overview

• Status: Recruiting
• Conditions: Intrauterine Adhesion
• Intervention / Treatment: Biological: hAESCs

Detailed Description

Asherman's syndrome is an gynecological disorder caused by the destruction of the endometrium due to repeated or aggressive curettages and/or endometritis. As a result, there is a loss of functional endometrium in multiple areas and the uterine cavity is obliterated by intrauterine adhesions, which results in amenorrhea, hypomenorrhea, infertility and recurrent pregnancy loss. Transcervical resection of adhesion (TCRA) is the main treatment for Asherman's syndrome; so far the effect is usually poor in moderate to severe refractory cases.

Human amniotic epithelial stem cells (hAESCs) are derived from human amniotic epithelium. hAESCs retain the characteristics approximating to embryonic stem cells. Animal experiments have shown that the endometrial thickness and fertility of mice was significantly improved after intrauterine therapy with hAESCs. To further explore the role of hAESCs in Asherman's syndrome patients, this project will evaluate the safety of hAESCs and find an effective treatment protocols.

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Wang Liang; Phone Number: 0571-88783738; Email: liangzi1126@126.com
• Study Contact Backup: Name: Liu Yang; Phone Number: 0571-88783738; Email: liuyangzheda@163.com

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310009
      • Recruiting
      • Second Affiliated Hospital, School of Medicine, Zhejiang University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• 1. Previously diagnosed as uterine adhesion, after the operation of TCRA and the postoperatively standardized hormonal replacement therapy(HRT) , recently diagnosed with refractory Asherman's syndrome or endometrial atrophy(EA);
• 2. According to the American Fertility Society(AFS) classification in 1988, patients are diagnosed of AS or EA stageⅢ-Ⅳ confirmed by hysteroscopy;
• 3. Elimination of infertility, recurrent spontaneous abortion or hypomenorrhea caused by other diseases;
• 4. Be willing to maintain an HRT cycle medication throughout the study, unless it is not tolerated;
• 5. Normal blood coagulation, liver, heart, and kidney function, absence of HIV, Hepatitis B or C, syphilis and psychiatric pathology;
• 6. Be willing to complete the study and sign the consent form.

Exclusion Criteria:

• 1. Patients with severe internal disease;
• 2. The patients are suffering from gynecologic inflammation or active genital tubercle bacillus;
• 3. The patient has other uterine diseases or the abnormal uterine cavity which can't be restored by surgery;
• 4. Infertility due to a man's cause;
• 5. The patient has a previous history of cancer and is undergoing radiotherapy or chemotherapy;
• 6. HIV positive
• 7. Active hepatitis B or C infection, syphilis seropositive
• 8. Laboratory routine check index abnormality, such as Hb（hemoglobin）<8.0 g/dL,WBC（white blood cell count）<3,000/ml, platelet counts<75 000/mm3, AST（glutamic oxalacetic transaminase）>ULN（upper limit of normal），ALT（Glutamic pyruvic transaminase）>ULN and so on;
• 9. Patients have any complications that may interfere with safety or efficacy or predict life expectancy of less than 24 months;
• 10. Mental illness in the past 6 months;
• 11. Patients have a history of drug or alcohol abuse or dependence in the past two years;
• 12. Unable or unwilling to give informed consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TCRA and intrauterine infusion of hAESCs; hAESCs is infused into uterine cavity after TCRA.	Biological: hAESCs; 5*10^7 hAESCs is infused into uterine cavity with TCRA on Day0, Day7 and after the first menstruation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
changes of Endometrial thickness	Measure the endometrial thickness during periovulatory period on ultrasound by the same trained medical sonographers at 1,3,6 and 9 months after surgery, comparing with pre-operation.	at the 1, 3，6 and 9 months after surgery
changes of Menstrual blood volume	Estimate the menstrual blood volume after surgery by the number of sanitary napkins per day and number of days to menstruation at 1, 3, 6, 9 months after surgery, which will be compared with pre-operation.	at the 1, 3，6 and 9 months after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
pregnancy rate	Ultrasound reveals that the fetus had a heart activity	24 months

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University
• Collaborators: Shanghai iCELL Biotechnology Co., Ltd, Shanghai, China
• Investigators: Principal Investigator: Wang Liang, The Second Affiliated Hospital of Medical College of Zhejiang University

Study record dates

Study Major Dates

• Study Start (Actual): September 16, 2020
• Primary Completion (Anticipated): September 1, 2022
• Study Completion (Anticipated): September 1, 2023

Study Registration Dates

• First Submitted: November 27, 2017
• First Submitted That Met QC Criteria: December 18, 2017
• First Posted (Actual): December 22, 2017

Study Record Updates

• Last Update Posted (Actual): October 28, 2020
• Last Update Submitted That Met QC Criteria: October 25, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Fibrosis; Cicatrix; Tissue Adhesions
• Other Study ID Numbers: 2017-080

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No