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

Phase 1

• Conditions: Primary Ovarian Insufficiency
• Interventions: Genetic: Cell therapy

• Registration Number: NCT03877471
• Lead Sponsor: Chinese Academy of Sciences

Brief Summary

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.

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 Timeline

• Study First Submitted: 2019-03-11
• Study First Submitted QC: 2019-03-14
• Study First Posted: 2019-03-15
• Study Start: 2019-04-03
• Primary Completion: 2020-07-01
• Status Verified: 2021-08
• Last Update Submitted: 2021-08-04
• Last Update Posted: 2021-08-05
• Study Completion: 2021-12-31

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: Female
• Target Recruitment: 28

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Medium dosage	Cell therapy	The medium dosage will inject 5 million MSC-like cells (in 100ul suspension) for each ovary.
High dosage	Cell therapy	The high dosage will inject 10 million MSC-like cells (in 100ul suspension) for each ovary.
Low dosage	Cell therapy	The low dosage will inject 2 million MSC-like cells (in 100ul suspension) for each ovary.

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

The First Affiliated Hospital of Zhengzhou University; 🇨🇳 Zhengzhou, Henan, China