Filgrastim for Premature Ovarian Insufficiency

Study Overview
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Brief Summary
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Filgrastim is a Granulocyte-Colony Stimulating factor (G-CSF). It is an FDA approved drug. Very small embryonic-like stem cells (VSELs) are found in the ovary. Animal studies showed that these cells are able to regenerate the affected ovary. Studies on mice have shown that Filgrastim result in recovery of oogenesis after chemotherapy-induced gonadal failure (in 2013, 2014, and 2015).

Detailed Description
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Premature ovarian insufficiency (POI) has no curative treatment until now. Filgrastim is an FDA approved Granulocyte-Colony Stimulating factor (G-CSF). Very small embryonic-like stem cells (VSELs) are found in the testis and ovary. VSELs are stem cells that have noticed to survive chemotherapy induced gonadal failure. Data from animal studies showed that stimulation of these stem cells result in generation of the affected gonads. Studies on mice have shown a promising stimulating effect of Filgrastim on recovery of spermatogenesis and oogenesis after chemotherapy-induced gonadal failure (in 2013, 2014, and 2015).

Official Title
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Filgrastim for Treatment of Premature Ovarian Insufficiency: Randomized Clinical Trial

Conditions
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Premature Ovarian Failure

Intervention / Treatment
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* Biological: Filgrastim
* Drug: Saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women with Premature Ovarian Insufficiency (POI): For the purpose of the research women is considered to have POI if she is aged less than 40 years and has amenorrhea of at least 4 month with FSH level above 25 IU/L (repeated twice >4 weeks apart). Exclusion Criteria: Abnormal karyotype Previous pelvic or abdominal radiotherapy Previous surgical removal of the ovarian pathology Chronic disease: renal, liver, cardiac, malignancy

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 40 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: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Filgrastim arm<br>Intervention: Filgrastim vial (30 million IU/ml) SC injection twice daily for five consecutive days | Biological: Filgrastim<br>* Each case will have two intervention phases done blindly at random with a wash-out period of 6 months: Phase A: Filgrastim vial (30 million IU/ml) SC injection twice daily for five consecutive days. Phase B: Injection of saline SC injection twice daily for five consecutive days.<br>* Other names: Granulocyte-Colony Stimulating Factor (G-CSF);|
| Placebo Comparator: Placebo arm<br>Intervention: Injection of saline SC injection twice daily for five consecutive days. | Drug: Saline<br>* Injection of saline SC injection twice daily for five consecutive days<br>* Other names: placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Return of menses | Return of menses in patients with amenorrhea of at least 4 months | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pregnancy | Occurrence of pregnancy as diagnosed by positive serum B-hCG and/or ultrasound | 6 months | 
| serum Estradiol | Normalization of serum Estradiol as tested bi-weekly | 6 months | 
| serum Anti-mullarian Hormone (AMH) | Normalization of serum AMH in patients with AMH level less than 0.9 ng/mL | 6 months | 
| serum FSH | Normalization of serum FSH in patients with FSH level above 25 IU/L | 6 months | 
| Follicular growth | Growth of follicle to size at least 18 mm as monitored by transvaginal ultrasound | 6 months | 
| endometrial thickness | increase of endometrial thickness in women with thin endometrium (less then 8 mm) | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Premature, Ovarian, Failure, Filgrastim