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

Sponsor

Chinese Academy of Sciences (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT03877471

Collaborator

The First Affiliated Hospital of Zhengzhou University (Other), National Natural Science Foundation of China (Other)

Enrollment

Location

Arms

Anticipated Duration (Months)

0.8

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Primary Ovarian Insufficiency	Genetic: Cell therapy	Phase 1

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 Design

Study Type:

Interventional

Actual Enrollment :

28 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

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.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.

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Apr 3, 2019

Actual Primary Completion Date :

Jul 1, 2020

Anticipated Study Completion Date :

Dec 31, 2021

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

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

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.
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 40 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

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

Exclusion Criteria:

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