Clinical trial NCT03877471: Mesenchymal Stem Cells (MSCs) - Like Cell Transplantation in Women With Primary Ovarian Insufficiency
Official title: Safety Study of Human Embryonic Stem Cell Derived Mesenchymal Stem Cell (MSC)-Like Cells Transplantation in Women With Primary Ovarian Insufficiency (POI)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Primary Ovarian Insufficiency
Keywords: Mesenchymal stem cell
Transplantation
Human embryonic stem cell
Premature ovarian failure
Lead sponsor: Chinese Academy of Sciences
Sponsor class: OTHER_GOV
Collaborators: name: The First Affiliated Hospital of Zhengzhou University
name: National Natural Science Foundation of China
First posted: 2019-03-15
Enrollment: 28
Sex: FEMALE
Maximum age (years): 40
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Patients will be subjected into 3 groups, with a low (0.2×107), medium (0.5×107) and high dosage (1.0×107) of cells transplantation for each ovary. The investigator will first carry out the low dosage group, and then the medium dosage group, based on the safety evaluation of the previous group, the high dosage group will be executed in the same way.
Primary purpose: TREATMENT

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).

Eligibility criteria: 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.

Primary outcomes:
measure: Temperature
timeFrame: 0-24 weeks
measure: Pulse
timeFrame: 0-24 weeks
measure: Breaths per minute
timeFrame: 0-24 weeks
measure: Blood pressure
timeFrame: 0-24 weeks
Secondary outcomes:
measure: Number of antral follicle
timeFrame: 0-24 weeks
measure: Follicle-stimulating hormone (FSH) serum level
timeFrame: 0-24 weeks
measure: Estradiol (E2) serum level
timeFrame: 0-24 weeks
measure: Anti-Mullerian hormone (AMH) serum level
timeFrame: 0-24 weeks
measure: Ovarian volume
timeFrame: 0-24 weeks
Other outcomes:
Locations:
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University
state: Henan
Study officials:
affiliation: Institute of Zoology, Chinese Academy of Sciences
name: Hongmei Wang, Doctor
role: PRINCIPAL_INVESTIGATOR
References: