Human Amniotic Epithelial Cells for Asherman's Syndrome

Safety and Therapeutic Effect of Human Amniotic Epithelial Cells in Severe Refractory Asherman's Syndrome

This project aims to investigate the safety and effectiveness of human amniotic epithelial cells in the treatment of the severe refractory Asherman's syndrome.

Study Overview

• Status: Unknown
• Conditions: Asherman's Syndrome
• Intervention / Treatment: Biological: hAECs; Biological: biological amnion

Detailed Description

Asherman's syndrome is a 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 cells (hAECs) are derived from human amniotic epithelium. hAECs retain the characteristics approximating to embryonic stem cells. Animal experiments have shown that the endometrial thickness and fertility of mice were significantly improved after intrauterine therapy with amniotic epithelial cells. To further explore the role of hAECs in Asherman's syndrome patients, this project plans to evaluate the safety of hAECs provided by Chongqing iCELL Biotechnology Co.,Ltd., which is a subsidiary of Shanghai iCELL Biotechnology Co.,Ltd., and find an effective treatment protocol.

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 1

Contacts and Locations

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 36 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• 1. Hysteroscopy examination confirms intrauterine adhesions, II -III according to the American Fertility Society (AFS) classification of uterine adhesions;
• 2. Regular Menstrual cycles and menstruation is normal before abortion or curettage;
• 3. Having a clear desire to fertility;
• 4. Normal blood coagulation, liver, heart, and kidney function, absence of HIV, Hepatitis B or C, syphilis and psychiatric pathology;
• 5. Serum β-hCG is negative;
• 6. Be willing to complete the study and sign the consent form.

Exclusion Criteria:

• 1. Having a history of malignant tumor;
• 2. Having other uterine diseases, such as, uterine fibroids, adenomyosis and uterine malformations;
• 3. Hysteroscopic adhesiolysis more than 3 times in the past;
• 4. Absence of peripheral vein access.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: biological amnion loaded with hAECs; Biological amnion loaded with 100 million hAECs is placed into uterine cavity immediately after TCRA.	Biological: hAECs; hAECs are provided by Chongqing iCELL Biotechnology Co.,Ltd., which is a subsidiary of Shanghai iCELL Biotechnology Co.,Ltd. The participants are blind to their arms because the surgery is done under anesthesia. After hysteroscopic adhesiolysis, subsequently oral antibiotics will be given for 3 days to prevent infection. Estrogen will be administrated for 3 cycles to stimulate the repair of endometrium after the surgery.
Placebo Comparator: biological amnion; Biological amnion is placed into uterine cavity immediately after TCRA.	Biological: biological amnion; Biological amnion is purchased from JiangXi RuiJi BioTechnology Co.,Ltd. The participants are blind to their arms because the surgery is done under anesthesia. After hysteroscopic adhesiolysis, subsequently oral antibiotics will be given for 3 days to prevent infection. Estrogen will be administrated for 3 cycles to stimulate the repair of endometrium after the surgery.
Experimental: intravenous infusion of hAECs; intravenous infusion of 100 million hAECs immediately after TCRA	Biological: hAECs; hAECs are provided by Chongqing iCELL Biotechnology Co.,Ltd., which is a subsidiary of Shanghai iCELL Biotechnology Co.,Ltd. The participants are blind to their arms because the surgery is done under anesthesia. After hysteroscopic adhesiolysis, subsequently oral antibiotics will be given for 3 days to prevent infection. Estrogen will be administrated for 3 cycles to stimulate the repair of endometrium after the surgery.
Experimental: intrauterine infusion of hAECs; 100 million hAECs is infused into uterine cavity immediately after TCRA.	Biological: hAECs; hAECs are provided by Chongqing iCELL Biotechnology Co.,Ltd., which is a subsidiary of Shanghai iCELL Biotechnology Co.,Ltd. The participants are blind to their arms because the surgery is done under anesthesia. After hysteroscopic adhesiolysis, subsequently oral antibiotics will be given for 3 days to prevent infection. Estrogen will be administrated for 3 cycles to stimulate the repair of endometrium after the surgery.
Experimental: hydrogel loaded with hAECs; Hydrogel loaded with 100 million hAECs is infused into uterine cavity immediately after TCRA.	Biological: hAECs; hAECs are provided by Chongqing iCELL Biotechnology Co.,Ltd., which is a subsidiary of Shanghai iCELL Biotechnology Co.,Ltd. The participants are blind to their arms because the surgery is done under anesthesia. After hysteroscopic adhesiolysis, subsequently oral antibiotics will be given for 3 days to prevent infection. Estrogen will be administrated for 3 cycles to stimulate the repair of endometrium after the surgery.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Menstrual blood volume	Estimate the menstrual blood volume after surgery by the number of sanitary napkins per day and number of days, which will be compared with pre-operation.	at 3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Endometrial thickness	Measure the endometrial thickness during periovulatory period on ultrasound by the same trained medical sonographers at 3 months after surgery, compared with pre-operation.	at 3 months
Uterine volume	Measure the uterine volume during periovulatory period on ultrasound by the same trained medical sonographers at 3 months after surgery, compared with pre-operation.	at 3 months
Ongoing pregnancy rate	A ongoing pregnancy means that at the 12th week of pregnancy, ultrasound reveals that the fetus had a heart beat and the size of the fetus is in consistent with the gestational week.	up to 24 months

Collaborators and Investigators

• Sponsor: The Second Affiliated Hospital of Chongqing Medical University
• Collaborators: Shanghai iCELL Biotechnology Co., Ltd, Shanghai, China
• Investigators: Study Chair: Lina Hu, The Second Affiliated Hospital of Chongqing Medical University; Principal Investigator: Chanyu Zhang, The Second Affiliated Hospital of Chongqing Medical University; Principal Investigator: Fan He, The Second Affiliated Hospital of Chongqing Medical University; Principal Investigator: Jianguo Hu, The Second Affiliated Hospital of Chongqing Medical University; Principal Investigator: Heng Zou, The Second Affiliated Hospital of Chongqing Medical University; Principal Investigator: Huijia Chen, The Second Affiliated Hospital of Chongqing Medical University

Publications and helpful links

General Publications

• Yu D, Wong YM, Cheong Y, Xia E, Li TC. Asherman syndrome--one century later. Fertil Steril. 2008 Apr;89(4):759-79. doi: 10.1016/j.fertnstert.2008.02.096.
• Ilancheran S, Moodley Y, Manuelpillai U. Human fetal membranes: a source of stem cells for tissue regeneration and repair? Placenta. 2009 Jan;30(1):2-10. doi: 10.1016/j.placenta.2008.09.009. Epub 2008 Nov 7.

Study record dates

Study Major Dates

• Study Start (Anticipated): October 1, 2017
• Primary Completion (Anticipated): September 1, 2019
• Study Completion (Anticipated): March 1, 2021

Study Registration Dates

• First Submitted: July 13, 2017
• First Submitted That Met QC Criteria: July 19, 2017
• First Posted (Actual): July 21, 2017

Study Record Updates

• Last Update Posted (Actual): July 21, 2017
• Last Update Submitted That Met QC Criteria: July 19, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease; Syndrome; Gynatresia
• Other Study ID Numbers: 2017-116

Drug and device information, study documents

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