Mesenchymal Stem Cells (MSCs) - Like Cell Transplantation in Women With Primary Ovarian Insufficiency (MSCLCTWPOI)

Safety Study of Human Embryonic Stem Cell Derived Mesenchymal Stem Cell (MSC)-Like Cells Transplantation in Women With Primary Ovarian Insufficiency (POI)

There is a high incidence of women suffering from Primary Ovarian Insufficiency (POI). So far, there was no treatment sufficient enough to cure POI. Cell therapy is a rapidly developing field and have shown immense promise in the treatment of ovarian dysfunction. In this study, the investigator will evaluate the safety of MSC-like cell therapy in women suffering from POI.

Study Overview

• Status: Active, not recruiting
• Conditions: Primary Ovarian Insufficiency
• Intervention / Treatment: Genetic: Cell therapy

Detailed Description

The purpose of this work is to explore the safety and preliminary efficacy of human embryonic stem cell derived MSC-like cell transplantation in women with POI. MSC-like cells were injected directly into bilateral ovaries under transvaginal ultrasound. Patients are subjected into 3 groups, with low (0.2×107), medium (0.5×107) and high dosage (1.0×107) of cells injection for each ovary. The outcomes of patients were followed after the injection every 2 weeks. The investigator mainly follow the safety indexes, and the level of sex hormone and signs of follicle growth will also be monitored. The growing follicles will be stimulated by exogenous hormone, followed by oocyte retrieval and in vitro fertilization (IVF).

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Henan
    • Zhengzhou, Henan, China, 450052
      • The First Affiliated Hospital of Zhengzhou University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 40 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Under 40 years of age;
2. Have established regular menstrual cycle, oligomenorrhea / amenorrhea ≥ 4 months;
3. FSH (Follicle-Stimulating Hormone) > 25 IU/mL;
4. Bilateral ovaries are visible by ultrasound;
5. Have fertility requirement, husband has sperms;
6. Willing to sign the Informed Consent Form.

Exclusion Criteria:

1. Primary amenorrhea;
2. History of serious drug allergy or allergic constitution;
3. Thrombophlebitis and thromboembolia, past and present;
4. Acute or chronic infection, hematologic disease, angiocardiopathy, pulmonary disease, liver disease, nephropathy, pancreas disease
5. Autoimmune disease, history of severe familial genetic disease, etc.
6. Anatomical abnormality of reproductive system;
7. Contraindications for pregnancy;
8. Spouse azoospermia;
9. HIV+, hepatitis B, C;
10. Thyroid dysfunction;
11. History of previous malignant or ovarian tumors, history of ovarian therapy;
12. Abnormal karyotyping (e.g. turner syndrome, fragile X syndrome);
13. During pregnancy or lactation;
14. Alcohol or other substance abuse;
15. Mental disease, communicate obstruction;
16. Unwilling to comply with follow-up schedule or want to take other treatment during the follow-up period;
17. Attending doctor consider inappropriate to take part in.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Low dosage; The low dosage will inject 2 million MSC-like cells (in 100ul suspension) for each ovary.	Genetic: Cell therapy; Ovary injection with MSC-like cells through transvaginal ultrasound,3 injection points for each ovary.
Experimental: Medium dosage; The medium dosage will inject 5 million MSC-like cells (in 100ul suspension) for each ovary.	Genetic: Cell therapy; Ovary injection with MSC-like cells through transvaginal ultrasound,3 injection points for each ovary.
Experimental: High dosage; The high dosage will inject 10 million MSC-like cells (in 100ul suspension) for each ovary.	Genetic: Cell therapy; Ovary injection with MSC-like cells through transvaginal ultrasound,3 injection points for each ovary.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Temperature	Body temperature of the participants will be measured fortnightly after injection.	0-24 weeks
Pulse	Pulse of the participants will be measured fortnightly after injection.	0-24 weeks
Breaths per minute	Breathing rate of the participants will be measured fortnightly after injection.	0-24 weeks
Blood pressure	Both systolic pressure and diastolic pressure of the participants will be assessed fortnightly after injection.	0-24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of antral follicle	The number of antral follicles developing will be recorded by transvaginal ultrasound fortnightly after injection.	0-24 weeks
Follicle-stimulating hormone (FSH) serum level	Serum FSH level will be tested fortnightly after injection.	0-24 weeks
Estradiol (E2) serum level	Serum E2 level will be tested fortnightly after injection.	0-24 weeks
Anti-Mullerian hormone (AMH) serum level	Serum AMH level will be tested fortnightly after injection.	0-24 weeks
Ovarian volume	The ovarian volume will be recorded fortnightly by transvaginal ultrasound after injection.	0-24 weeks

Collaborators and Investigators

• Sponsor: Chinese Academy of Sciences
• Collaborators: National Natural Science Foundation of China; The First Affiliated Hospital of Zhengzhou University
• Investigators: Principal Investigator: Hongmei Wang, Doctor, Institute of zoology, Chinese Academy of Sciences

Study record dates

Study Major Dates

• Study Start (Actual): April 3, 2019
• Primary Completion (Actual): July 1, 2020
• Study Completion (Anticipated): December 31, 2021

Study Registration Dates

• First Submitted: March 11, 2019
• First Submitted That Met QC Criteria: March 14, 2019
• First Posted (Actual): March 15, 2019

Study Record Updates

• Last Update Posted (Actual): August 5, 2021
• Last Update Submitted That Met QC Criteria: August 4, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: Mesenchymal stem cell; Transplantation; Human embryonic stem cell; Premature ovarian failure
• Additional Relevant MeSH Terms: Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Primary Ovarian Insufficiency; Menopause, Premature
• Other Study ID Numbers: IOZ ChineseAS POI-2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: The investigator have not recruited enough participant yet, till now, most of them would like to keep the individual participant data classified.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No