A Therapeutic Trial of Human Amniotic Epithelial Cells Transplantation for Primary Ovarian Failure

Infertility Clinical Trial

— POF  

Official title:

A Therapeutic Trial of Human Amniotic Epithelial Cells Transplantation for Primary Ovarian Failure

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02912104
• Other study ID #: 20152236
• Status: Completed
• Phase: Phase 1
• Start date: June 20, 2020
• Est. completion date: January 5, 2023

Study information

• Verified date: February 2023
• Source: International Peace Maternity and Child Health Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This project will clarify the safety and effectiveness of human amniotic epithelial cells transplantation for the treatment of primary ovarian failure (POF) patients and provide a new therapeutic method for patients with infertility.

Description:

POF is a defect characterized by the premature depletion of ovarian follicles. Patients with POF suffer from amenorrhea, infertility, low levels of estrogen, and high gonadotropin concentration before the age of 40. The early failure of ovarian function leads to lost fertility and increases risk of osteoporosis and cardiovascular disease, which has serious impact on the patient's physical, mental health and family stability. The etiology of POF is complex, and so far there has not been any effective treatment. Recent study showed that human amniotic epithelial cells (hAECs), also known as the birth waste, are newly discovered adult stem cells. The hAECs have the ability to repair nerve damage, myocardial injury, as well as liver damage. hAECs have low immunogenicity and no ethical restrictions. Therefore, hAECs are expected to become the new seed cells for regenerative medicine. Our previous study was the first to show that human amniotic epithelial cells have the ability to restore folliculogenesis in a mouse model with chemotherapy-induced premature ovarian failure. Our further studies demonstrated that hAECs either directly transdifferentiated into granulosa cells, or inhibited tumor necrosis factor-alpha-mediated granulosa cell apoptosis and reduced the inflammatory reaction in ovaries induced by chemotherapeutics, regulating VEGFA and its receptors to induce follicular growth related to paracrine activity. Therefore, it is necessary to start the clinical study of human amniotic epithelial cells transplantation in the POF disease which may offer a novel therapeutic strategy for improving the quality of life of POF patients.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: January 5, 2023
• Est. primary completion date: January 5, 2022
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 45 Years

Eligibility

Inclusion Criteria:

1. =18 and<45 years old.

2. Female patients with documented diagnosis of POF: <40 years old, at least 4 months of amenorrhea not due to pregnancy, two FSH levels above 40 IU/L, at least one month apart.

3. Not in other trial within 3 months prior to the start of this trial.

4. Willing to participate in this trial and to give informed consent/assent before any procedures are performed in this trial.

Exclusion Criteria:

1. History of, or evidence of current malignancy within the past 5 years.

2. Severe functional impairment of vital organs.

3. Abnormal karyotype.

4. Coagulation disorders.

5. Severe pelvic adhesions.

6. Uncontrolled acute or chronic gynecologic inflammation.

7. Congenital adrenal cortical hyperplasia.

8. Cushing's syndrome.

9. Thyroid dysfunction.

10. Pituitary adenoma.

11. Pituitary amenorrhea or Hypothalamic amenorrhea.

12. Thrombophlebitis, venous thrombosis or artery thrombosis.

13. History of Oophorocystectomy.

14. Currently pregnant or breast-feeding.

15. Currently receiving other treatment that might affect the efficacy and safety of stem cells.

16. History of severe drug allergy.

17. Active infection detected by chest X-ray/CT.

18. HIV, TPAb positive.

19. Mental illness.

20. Currently participating in any other clinical trial that uses interventional drugs or examinations.

21. Patients that are deemed, by the investigator, inappropriate to participate in this trial.

Related Conditions & MeSH terms

• Infertility
• Menopause, Premature
• Premature Ovarian Failure
• Primary Ovarian Insufficiency

Intervention

Biological:
• human amniotic epithelial cells (hAECs) transplantation
hAECs are prepared and cultured using GMP(Good Manufacturing Practice, GMP) rules, 3×10^7 hAECs in 4.5ml is separately injected into ovarian tissue by bilateral ovarian artery infusion.

Locations

Country	Name	City	State
China	The International Peace Maternity and Child Health Hospital	Shanghai	Shanghai

Sponsors (2)

Lead Sponsor	Collaborator
International Peace Maternity and Child Health Hospital	Shanghai iCELL Biotechnology Co., Ltd, Shanghai, China

Country where clinical trial is conducted

China, 

References & Publications (3)

Wang F, Wang L, Yao X, Lai D, Guo L. Human amniotic epithelial cells can differentiate into granulosa cells and restore folliculogenesis in a mouse model of chemotherapy-induced premature ovarian failure. Stem Cell Res Ther. 2013 Oct 14;4(5):124. doi: 10. — View Citation

Yao X, Guo Y, Wang Q, Xu M, Zhang Q, Li T, Lai D. The Paracrine Effect of Transplanted Human Amniotic Epithelial Cells on Ovarian Function Improvement in a Mouse Model of Chemotherapy-Induced Primary Ovarian Insufficiency. Stem Cells Int. 2016;2016:414892 — View Citation

Zhang Q, Xu M, Yao X, Li T, Wang Q, Lai D. Human amniotic epithelial cells inhibit granulosa cell apoptosis induced by chemotherapy and restore the fertility. Stem Cell Res Ther. 2015 Aug 25;6(1):152. doi: 10.1186/s13287-015-0148-4. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety and Tolerability assessed by Adverse Events	Proportion of patients with adverse events (AEs), serious adverse events (SAEs) and adverse events of special interest (AESI,such as acute allergic reaction, ectopic mass formation related to treatment)	150 days
Secondary	Change from baseline in bilateral ovarian volume	The ovarian volume will be assessed by pelvic ultrasound on 30th, 90th, 150th days after transplantation.	150 days
Secondary	Change from baseline in number of antral follicles (AFC)	The number of antral follicles developing will be assessed by pelvic ultrasound on 30th, 90th, 150th days after transplantation.	150 days
Secondary	Change from baseline in Follicle-stimulating hormone (FSH) serum level	Serum FSH level will be tested on 30th and 150th days after transplantation.	150 days
Secondary	Change from baseline in Luteinizing hormone (LH), Estradiol (E2), Testosterone (T), Prolactin (PRL) , Anti-müllerian hormone (AMH) serum level	Serum LH, E2, T, PRL, AMH level will be tested on 30th and 150th days after transplantation.	150 days
Secondary	Menstruation resumption	Patients will monitor for resumption of menses within 150 days after transplantation. If the menstruation resumption rate is over 30%, the treatment will be considered effective.	150 days
Secondary	Endometrial thickness	The endometrial thickness will be assessed by pelvic ultrasound on 30th, 90th, 150th days after transplantation.	150 days
Secondary	Bone mineral density (BMD) measurements	The BMD will be tested on 150th day after transplantation.	150 days
Secondary	Achievement of pregnancy	Achievement of pregnancy by natural or assisted conception methods, such as in vitro fertilization (IVF). The outcomes of pregnancy include conception, miscarriage and delivery.; If the pregnancy rate is over 30%, the treatment will be considered effective.	12 Months