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

February 27, 2023 updated by: Dongmei Lai, International Peace Maternity and Child Health Hospital
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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

36

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Shanghai
      • Shanghai, Shanghai, China, 200030
        • The International Peace Maternity and Child Health Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 45 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety and Tolerability assessed by Adverse Events
Time Frame: 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)
150 days

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

International Peace Maternity and Child Health Hospital

Collaborators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 20, 2020

Primary Completion (Actual)

January 5, 2022

Study Completion (Actual)

January 5, 2023

Study Registration Dates

First Submitted

September 6, 2016

First Submitted That Met QC Criteria

September 20, 2016

First Posted (Estimate)

September 23, 2016

Study Record Updates

Last Update Posted (Actual)

March 1, 2023

Last Update Submitted That Met QC Criteria

February 27, 2023

Last Verified

February 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 20152236

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

The public can require the data and protocol from clinicaltrials.gov posted by investigator

IPD Sharing Time Frame

2 years

IPD Sharing Access Criteria

public

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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