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Autologous Bone Marrow Stem Cell Ovarian Transplantation to Restore Ovarian Function in Premature Ovarian Failure (ASCOT-2)

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ClinicalTrials.gov Identifier: NCT03535480
Recruitment Status : Not yet recruiting
First Posted : May 24, 2018
Last Update Posted : May 24, 2018
Sponsor:
Information provided by (Responsible Party):
Antonio Pellicer, Instituto de Investigacion Sanitaria La Fe

Tracking Information
First Submitted Date  ICMJE May 2, 2018
First Posted Date  ICMJE May 24, 2018
Last Update Posted Date May 24, 2018
Estimated Study Start Date  ICMJE June 2018
Estimated Primary Completion Date June 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 22, 2018)
Antral follicle count (AFC) [ Time Frame: 6 months ]
every antral follicle is measured
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: May 22, 2018)
  • Time to Menses recovery [ Time Frame: 6 months ]
    Spontaneous menstrual cycle restoration and its characteristics
  • serum follicle stimulating hormone (FSH) and estradiol [ Time Frame: 6 months ]
    serum extraction for biological measurements
  • ovarian reserve dynamics [ Time Frame: 6 months ]
    ultrasound observation of follicular development
  • Controlled Ovarian Hyperstimulation (COH) response [ Time Frame: 6 months ]
    ovarian response to gonadotropins
  • pregnancy rate [ Time Frame: 2 years ]
    pregnancy rate spontaneous and after COH
  • Number of good quality embryos [ Time Frame: 6 months ]
    Morphological criteria and developmental potential
  • Number of participants with treatment-related adverse events [ Time Frame: 6 months ]
    Secondary effects of the received interventions following hematological and gynecological medical criteria
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Autologous Bone Marrow Stem Cell Ovarian Transplantation to Restore Ovarian Function in Premature Ovarian Failure
Official Title  ICMJE Autologous Stem Cell Ovarian Transplantation to Restore Ovarian Function in Premature Ovarian Failure Patients. Pilot Study ASCOT-2
Brief Summary This study aims to recover ovarian function in POF/POI patients. With this pueprose we designed a study protocol including two arms: ASCOT arm, were patients receive the stem cell mobilization treatment with Granulocyte colony stimulating factor (G-CSF) followed by apheresis and ovarian artery catheterism to selectively infuse the stem cells into the ovary and the G-CSF arm including patients that receive the mobilization treatment but not the ovarian artery catheterism to selectively infuse the cells into the ovary.
Detailed Description

Ovarian aging appears early in life as a decline in function at 30s leading to a complete ovarian failure around 51 years of age in women. Women in modern society have delayed the age of childbearing due to socioeconomic changes and patient´s age has become the main determinant of infertility, since it is well known that both quantity and quality of the oocytes from aging patients are seriously impaired. Nevertheless, the low ovarian reserve is not only associated with age. Primary ovarian insufficiency (POI) is a cause of infertility in women, affecting 1% of the population. It is characterized by amenorrhea, hypoestrogenism, and elevated gonadotropin levels in women younger than 40 years of age. Impairment of ovarian function in POI can be mixed up with a low ovarian reserve or poor ovarian response although represent different clinical entities and patients.

Thus, interventions to recover damaged gonads in POI patients should be developed in order to enhance their reproductive potential. Clinically, bone marrow (BM) transplant in patients with POI due to chemotherapy treatment rescues ovarian functions as demonstrated by several spontaneous pregnancies. Previous research demonstrates that autologous stem cell ovarian transplantation (ASCOT) improves ovarian reserve (AMH and AFC) in 81% of women. Three of the eleven included patients achieve 5 pregnancies and 3 healthy babies have born. Response is highly variable between patients and molecular mechanisms still unknown. New approach is mandatory to elucidate them.

Results obtained in our premature ovarian failure (POF) animal model (included chemotherapy, CT ovarian injury) demonstrate that bone marrow stem cells restore ovulation by means of increasing vascularization, proliferation and diminishing apoptosis within the ovarian niche. These ovarian niche improvements promotes follicular development, increased number of antral and preovulatory follicles and corpus luteum.

POF model is ideal to demonstrate effectivity of ASCOT technique as they represent the worst possible scene. Any improvement in those patients should be significant.

Trying to be less invasive, we designed a study protocol including two arms: ASCOT arm as previously described and Granulocyte colony stimulating factor (G-CSF) arm including patients that receive the treatment but not the apheresis nor the ovarian artery catheterism to selectively infuse the cells into the ovary.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Investigator)
Primary Purpose: Treatment
Condition  ICMJE Premature Ovarian Failure (POF)
Intervention  ICMJE
  • Drug: G-CSF
    G-CSF subcutaneously during five days
    Other Name: Granulocyte colony stimulating factor
  • Combination Product: ASCOT
    G-CSF subcutaneously during five days, aphaeresis to hematopoietic stem cell collection and catheterism for ovarian artery infusion
Study Arms  ICMJE
  • Experimental: G-CSF
    Only receives G-CSF subcutaneously five days for stem cell mobilization
    Intervention: Drug: G-CSF
  • Experimental: ASCOT
    Receives G-CSF subcutaneously five days and then plasmapheresis for hematopoietic stem cell collection and catheterism for infusion in ovarian artery
    Interventions:
    • Drug: G-CSF
    • Combination Product: ASCOT
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: May 22, 2018)
20
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 2022
Estimated Primary Completion Date June 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • ≤ 38 years old
  • Oligo/Amenorrhea at least 4 months.
  • Serum FSH > 25 IU/l, AMH < 5picomols (pM)
  • Standard criteria for autologous bone marrow transplantation of our hospital.

Exclusion Criteria:

  • Ovarian endometriosis
  • Any ovarian surgery considered as risk factor of poor reserve.
  • Genetic factors associated with poor ovarian reserve (Turner syndrome, FMR1 premutations…)
  • Acquired poor ovarian reserve (Chemotherapy, radiotherapy...)
  • BMI ≥ 30kg/m2.
  • Iodine allergy
  • Kidney failure
  • Severe male factor
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years to 38 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Contact: Monica Romeu, Doctor +34961244000 ext 244116 monicaromeuvillarroya@gmail.com
Contact: Susana Martinez, Doctor +34961244000 ext 244116 susamc12@hotmail.com
Listed Location Countries  ICMJE Spain
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03535480
Other Study ID Numbers  ICMJE 2017/0251
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Antonio Pellicer, Instituto de Investigacion Sanitaria La Fe
Study Sponsor  ICMJE Instituto de Investigacion Sanitaria La Fe
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Antonio Pellicer, Professor IIS la Fe
PRS Account Instituto de Investigacion Sanitaria La Fe
Verification Date May 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP