Clinical trial NCT02912104: A Therapeutic Trial of Human Amniotic Epithelial Cells Transplantation for Primary Ovarian Failure
Official title: A Therapeutic Trial of Human Amniotic Epithelial Cells Transplantation for Primary Ovarian Failure
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Primary Ovarian Insufficiency
Premature Ovarian Failure
Infertility
Keywords: primary ovarian insufficiency
premature ovarian failure
Infertility
human amniotic epithelial cells transplantation
Lead sponsor: International Peace Maternity and Child Health Hospital
Sponsor class: OTHER
Collaborators: name: Shanghai iCELL Biotechnology Co., Ltd, Shanghai, China
First posted: 2016-09-23
Enrollment: 36
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Safety and Tolerability assessed by Adverse Events
timeFrame: 150 days
Secondary outcomes:
measure: Change from baseline in bilateral ovarian volume
timeFrame: 150 days
measure: Change from baseline in number of antral follicles (AFC)
timeFrame: 150 days
measure: Change from baseline in Follicle-stimulating hormone (FSH) serum level
timeFrame: 150 days
measure: Change from baseline in Luteinizing hormone (LH), Estradiol (E2), Testosterone (T), Prolactin (PRL) , Anti-müllerian hormone (AMH) serum level
timeFrame: 150 days
measure: Menstruation resumption
timeFrame: 150 days
measure: Endometrial thickness
timeFrame: 150 days
measure: Bone mineral density (BMD) measurements
timeFrame: 150 days
measure: Achievement of pregnancy
timeFrame: 12 Months
Other outcomes:
Locations:
city: Shanghai
country: China
facility: The International Peace Maternity and Child Health Hospital
state: Shanghai
Study officials:
affiliation: The center of Laboratory, The international peace Maternity and child health Hospital,School of Medicine, Shanghai Jiaotong University, Shanghai,China,200030
name: Dongmei Lai, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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: 10.1186/scrt335.
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.
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;2016:4148923. doi: 10.1155/2016/4148923. Epub 2015 Nov 9.