The Use of Expandeded Mesenchymal Stromal Cells (MSC) in Premature Ovarian Failure (POF) in Adult Humans

Phase 1

Active, not recruiting

• Conditions: Premature Ovarian Failure
• Interventions: Biological: expanded autologous bone marrow derived MSC Intravaginally; Biological: EV; Biological: expanded autologous bone marrow derived MSC Laporoscopic; Biological: expanded autologous bone marrow derived MSC

• Registration Number: NCT04815213
• Lead Sponsor: University of Jordan

Brief Summary

Autologous bone marrow-derived mesenchymal cells will be injected into patients diagnosed with premature ovarian failure

Detailed Description

MSCs in passage-2 culture will be washed with PBS and detached with trypsin/EDTA (0.25%). After that, the cells will be suspended at a density of 20×106 cells/ 2 ml normal saline and loaded into 3 ml sterile syringes.

The cells should be infused within 2 hours of release. Tests and follow up are to be monthly.

Study Timeline

• Study First Submitted: 2021-03-02
• Study First Submitted QC: 2021-03-22
• Study First Posted: 2021-03-24
• Study Start: 2022-01-01
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-23
• Last Update Posted: 2025-01-28
• Primary Completion: 2025-01-31
• Study Completion: 2027-01-31

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: Female
• Target Recruitment: 10

Inclusion Criteria

1. Signed and dated informed consent
2. Married female, 18-38 years old
3. Diagnosis of premature ovarian insufficiency: At least two menopausal FSH levels (≥ 20 IU/L) and/or Primary or secondary amenorrhea at least for 6 months
4. Evidence of low ovarian reserve defined as: AMH < _0.3 ng/ML & FSH >20 IU/L, AFC < 4, and/or failure of prior attempts of assisted reproductive techniques due to limited ovarian response (poor responder).
5. Normal karyotype 46, XX.
6. Presence of at least one ovary
7. Normal thyroid function as evidence by normal serum Thyroid Stimulating Hormone (TSH) levels.
8. Agree to report any pregnancy to the research staff immediately.
9. Cooperative patient
10. Negative for infectious panel (HIV, HBV, HCV, and VDRL)

Exclusion Criteria

1. Currently breast-feeding
2. Has a history of, or evidence of current malignancy
3. Major mental health disorder that precludes participation in the study
4. Current or recent (within the past 2 weeks) use of the following medications: Oral or systemic corticosteroids, Hormones (estrogen, progestins, oral contraceptives), Danazol, anticoagulants, herbal or botanical supplements with possible hormonal effects. Washout will be allowed.
5. Type I or Type II diabetes mellitus, or if receiving antidiabetic medications
6. Significant anemia (Hemoglobin <8 g/dL).
7. Untreated deep venous thrombosis, and/or pulmonary embolus
8. Known heart disease (New York Heart Association Class II or higher).
9. Known Liver disease (defined as Aspartate Aminotransferase (AST) or Alanine Aminotransferase (ALT)>2 times normal, or total bilirubin >2.5 mg/dL).
10. Known Renal disease (defined as Blood urea nitrogen (BUN)>30 mg/dL or serum creatinine > 1.6 mg/dL).
11. Clinically active autoimmune condition

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
MSCs Intravaginally	expanded autologous bone marrow derived MSC Intravaginally	Expanded autologous bone marrow-derived mesenchymal cells (BMMSCs), dose 20 million cells/ovary Inravaginally
EV	EV	Extravascular vesicles (EV) injection
MSCs Laparoscopic	expanded autologous bone marrow derived MSC Laporoscopic	Expanded autologous bone marrow-derived mesenchymal cells (BMMSCs), dose 20 million cells/ovary Laparoscopic
Arm 1	expanded autologous bone marrow derived MSC	Expanded autologous bone marrow-derived mesenchymal cells (BMMSCs), dose 20 million cells/ovary

Primary Outcome Measures

Name	Time	Method
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]	12 months	Treatment adverse events are defined by any adverse event leading to hospitalization, organ failure or death

Secondary Outcome Measures

Name	Time	Method
Number of patients with enhanced hormonal profile, ovarian changes and endometrial changes	12 months	Efficacy will be measured comparing hormonal changes (FSH, LH, AMH, estradiol) in patients' blood on monthly intervals
Number of patients with positive ovarian changes	12 months	Patients ultrasounds of the ovaries will compare size and follicle numbers
Number of patients with increased endometrial thickness	12 months	Ultrasounds of uterus will be compared for endometrial thickness

Trial Locations

Locations (1)

Cell Therapy Center, University of Jordan; 🇯🇴 Amman, Jordan