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

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

Detailed Description
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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.

Official Title
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The Use of Expanded Mesenchymal Stromal Cells (MSC) in Premature Ovarian Failure (POF) in Adult Humans: Phase I Clinical Trial

Conditions
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Premature Ovarian Failure

Intervention / Treatment
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* Biological: expanded autologous bone marrow derived MSC


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed and dated informed consent Married female, 18-38 years old 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 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). Normal karyotype 46, XX. Presence of at least one ovary Normal thyroid function as evidence by normal serum Thyroid Stimulating Hormone (TSH) levels. Agree to report any pregnancy to the research staff immediately. Cooperative patient Negative for infectious panel (HIV, HBV, HCV, and VDRL) Exclusion Criteria: Currently breast-feeding Has a history of, or evidence of current malignancy Major mental health disorder that precludes participation in the study 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. Type I or Type II diabetes mellitus, or if receiving antidiabetic medications Significant anemia (Hemoglobin <8 g/dL). Untreated deep venous thrombosis, and/or pulmonary embolus Known heart disease (New York Heart Association Class II or higher). Known Liver disease (defined as Aspartate Aminotransferase (AST) or Alanine Aminotransferase (ALT)>2 times normal, or total bilirubin >2.5 mg/dL). Known Renal disease (defined as Blood urea nitrogen (BUN)>30 mg/dL or serum creatinine > 1.6 mg/dL). Clinically active autoimmune condition

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 38 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1<br>Expanded autologous bone marrow-derived mesenchymal cells (BMMSCs), dose 20 million cells/ovary | Biological: expanded autologous bone marrow derived MSC<br>* Autologous bone marrow-derived mesenchymal cells (BMMSCs), dose 20 million cells/ovary<br>* Other names: BM-MSc;|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

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