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

Sponsor

International Peace Maternity and Child Health Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT02912104

Collaborator

Shanghai iCELL Biotechnology Co., Ltd, Shanghai, China (Industry)

Enrollment

Location

Arm

23.4

Anticipated Duration (Months)

1.5

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Primary Ovarian Insufficiency Premature Ovarian Failure Infertility	Biological: human amniotic epithelial cells (hAECs) transplantation	Phase 1

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

36 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jun 20, 2020

Anticipated Primary Completion Date :

Jun 1, 2022

Anticipated Study Completion Date :

Jun 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: hAECs transplantation To clarify the safety and effectiveness of human amniotic epithelial cells transplantation for the treatment of POF patients	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. Other Names: hAECs transplantation

Arm

Intervention/Treatment

Experimental: hAECs transplantation

To clarify the safety and effectiveness of human amniotic epithelial cells transplantation for the treatment of POF patients

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.

Other Names:

hAECs transplantation

Outcome Measures

Primary Outcome Measures

Safety and Tolerability assessed by Adverse Events [150 days]
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)

Secondary Outcome Measures

Change from baseline in bilateral ovarian volume [150 days]
The ovarian volume will be assessed by pelvic ultrasound on 30th, 90th, 150th days after transplantation.
Change from baseline in number of antral follicles (AFC) [150 days]
The number of antral follicles developing will be assessed by pelvic ultrasound on 30th, 90th, 150th days after transplantation.
Change from baseline in Follicle-stimulating hormone (FSH) serum level [150 days]
Serum FSH level will be tested on 30th and 150th days after transplantation.
Change from baseline in Luteinizing hormone (LH), Estradiol (E2), Testosterone (T), Prolactin (PRL) , Anti-müllerian hormone (AMH) serum level [150 days]
Serum LH, E2, T, PRL, AMH level will be tested on 30th and 150th days after transplantation.
Menstruation resumption [150 days]
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.
Endometrial thickness [150 days]
The endometrial thickness will be assessed by pelvic ultrasound on 30th, 90th, 150th days after transplantation.
Bone mineral density (BMD) measurements [150 days]
The BMD will be tested on 150th day after transplantation.
Achievement of pregnancy [12 Months]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 45 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

≥18 and<45 years old.
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.
Not in other trial within 3 months prior to the start of this trial.
Willing to participate in this trial and to give informed consent/assent before any procedures are performed in this trial.

Exclusion Criteria:

History of, or evidence of current malignancy within the past 5 years.
Severe functional impairment of vital organs.
Abnormal karyotype.
Coagulation disorders.
Severe pelvic adhesions.
Uncontrolled acute or chronic gynecologic inflammation.
Congenital adrenal cortical hyperplasia.
Cushing's syndrome.
Thyroid dysfunction.
Pituitary adenoma.
Pituitary amenorrhea or Hypothalamic amenorrhea.
Thrombophlebitis, venous thrombosis or artery thrombosis.
History of Oophorocystectomy.
Currently pregnant or breast-feeding.
Currently receiving other treatment that might affect the efficacy and safety of stem cells.
History of severe drug allergy.
Active infection detected by chest X-ray/CT.
HIV, TPAb positive.
Mental illness.
Currently participating in any other clinical trial that uses interventional drugs or examinations.
Patients that are deemed, by the investigator, inappropriate to participate in this trial.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The International Peace Maternity and Child Health Hospital	Shanghai	Shanghai	China	200030

Sponsors and Collaborators

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

Investigators

Principal Investigator: Dongmei Lai, M.D., The center of Laboratory, The international peace Maternity and child health Hospital,School of Medicine, Shanghai Jiaotong University, Shanghai,China,200030