Filgrastim for Premature Ovarian Insufficiency

Premature Ovarian Failure Clinical Trial

— FIL-POI  

Official title:

Filgrastim for Treatment of Premature Ovarian Insufficiency: Randomized Clinical Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02783937
• Other study ID #: OBGYN001
• Status: Completed
• Phase: Phase 4
• Start date: November 2016
• Est. completion date: June 2021

Study information

• Verified date: September 2021
• Source: South Valley University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

Description:

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: June 2021
• Est. primary completion date: December 2020
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 16 Years to 40 Years

Eligibility

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

Related Conditions & MeSH terms

• Menopause, Premature
• Premature Birth
• Premature Ovarian Failure
• Primary Ovarian Insufficiency

Intervention

Biological:
• Filgrastim
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.

Drug:
• Saline
Injection of saline SC injection twice daily for five consecutive days

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
South Valley University

References & Publications (5)

Akdemir A, Zeybek B, Akman L, Ergenoglu AM, Yeniel AO, Erbas O, Yavasoglu A, Terek MC, Taskiran D. Granulocyte-colony stimulating factor decreases the extent of ovarian damage caused by cisplatin in an experimental rat model. J Gynecol Oncol. 2014 Oct;25(4):328-33. doi: 10.3802/jgo.2014.25.4.328. Epub 2014 Jun 18. — View Citation

Benavides-Garcia R, Joachim R, Pina NA, Mutoji KN, Reilly MA, Hermann BP. Granulocyte colony-stimulating factor prevents loss of spermatogenesis after sterilizing busulfan chemotherapy. Fertil Steril. 2015 Jan;103(1):270-80.e8. doi: 10.1016/j.fertnstert.2014.09.023. Epub 2014 Nov 5. — View Citation

Bhartiya D, Anand S, Parte S. VSELs may obviate cryobanking of gonadal tissue in cancer patients for fertility preservation. J Ovarian Res. 2015 Nov 17;8:75. doi: 10.1186/s13048-015-0199-2. — View Citation

Roness H, Kalich-Philosoph L, Meirow D. Prevention of chemotherapy-induced ovarian damage: possible roles for hormonal and non-hormonal attenuating agents. Hum Reprod Update. 2014 Sep-Oct;20(5):759-74. doi: 10.1093/humupd/dmu019. Epub 2014 May 15. Review. — View Citation

Skaznik-Wikiel ME, McGuire MM, Sukhwani M, Donohue J, Chu T, Krivak TC, Rajkovic A, Orwig KE. Granulocyte colony-stimulating factor with or without stem cell factor extends time to premature ovarian insufficiency in female mice treated with alkylating chemotherapy. Fertil Steril. 2013 Jun;99(7):2045-54.e3. doi: 10.1016/j.fertnstert.2013.01.135. Epub 2013 Feb 26. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Return of menses	Return of menses in patients with amenorrhea of at least 4 months	6 months
Secondary	Pregnancy	Occurrence of pregnancy as diagnosed by positive serum B-hCG and/or ultrasound	6 months
Secondary	serum Estradiol	Normalization of serum Estradiol as tested bi-weekly	6 months
Secondary	serum Anti-mullarian Hormone (AMH)	Normalization of serum AMH in patients with AMH level less than 0.9 ng/mL	6 months
Secondary	serum FSH	Normalization of serum FSH in patients with FSH level above 25 IU/L	6 months
Secondary	Follicular growth	Growth of follicle to size at least 18 mm as monitored by transvaginal ultrasound	6 months
Secondary	endometrial thickness	increase of endometrial thickness in women with thin endometrium (less then 8 mm)	6 months