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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

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.

Condition or disease Intervention/treatment Phase
Premature Ovarian Failure (POF) Drug: G-CSF Combination Product: ASCOT Phase 4

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Investigator)
Primary Purpose: Treatment
Official Title: Autologous Stem Cell Ovarian Transplantation to Restore Ovarian Function in Premature Ovarian Failure Patients. Pilot Study ASCOT-2
Estimated Study Start Date : June 2018
Estimated Primary Completion Date : June 2020
Estimated Study Completion Date : June 2022


Arm Intervention/treatment
Experimental: G-CSF
Only receives G-CSF subcutaneously five days for stem cell mobilization
Drug: G-CSF
G-CSF subcutaneously during five days
Other Name: Granulocyte colony stimulating factor

Experimental: ASCOT
Receives G-CSF subcutaneously five days and then plasmapheresis for hematopoietic stem cell collection and catheterism for infusion in ovarian artery
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




Primary Outcome Measures :
  1. Antral follicle count (AFC) [ Time Frame: 6 months ]
    every antral follicle is measured


Secondary Outcome Measures :
  1. Time to Menses recovery [ Time Frame: 6 months ]
    Spontaneous menstrual cycle restoration and its characteristics

  2. serum follicle stimulating hormone (FSH) and estradiol [ Time Frame: 6 months ]
    serum extraction for biological measurements

  3. ovarian reserve dynamics [ Time Frame: 6 months ]
    ultrasound observation of follicular development

  4. Controlled Ovarian Hyperstimulation (COH) response [ Time Frame: 6 months ]
    ovarian response to gonadotropins

  5. pregnancy rate [ Time Frame: 2 years ]
    pregnancy rate spontaneous and after COH

  6. Number of good quality embryos [ Time Frame: 6 months ]
    Morphological criteria and developmental potential

  7. Number of participants with treatment-related adverse events [ Time Frame: 6 months ]
    Secondary effects of the received interventions following hematological and gynecological medical criteria



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Ages Eligible for Study:   18 Years to 38 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03535480


Contacts
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Contact: Monica Romeu, Doctor +34961244000 ext 244116 monicaromeuvillarroya@gmail.com
Contact: Susana Martinez, Doctor +34961244000 ext 244116 susamc12@hotmail.com

Locations
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Spain
Hospital Universitario y Politécnico la Fe-IIS la Fe Not yet recruiting
Valencia, Spain, 46026
Principal Investigator: Sonia Herraiz, PhD         
Sub-Investigator: Nuria Pellicer de Castellví, Doctor         
Sub-Investigator: Inés Gómez, Doctor         
Sponsors and Collaborators
Instituto de Investigacion Sanitaria La Fe
Investigators
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Principal Investigator: Antonio Pellicer, Professor IIS la Fe

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Responsible Party: Antonio Pellicer, Professor, Instituto de Investigacion Sanitaria La Fe
ClinicalTrials.gov Identifier: NCT03535480     History of Changes
Other Study ID Numbers: 2017/0251
First Posted: May 24, 2018    Key Record Dates
Last Update Posted: May 24, 2018
Last Verified: May 2018

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Antonio Pellicer, Instituto de Investigacion Sanitaria La Fe:
ovarian reserve

Additional relevant MeSH terms:
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Premature Birth
Primary Ovarian Insufficiency
Menopause, Premature
Obstetric Labor, Premature
Obstetric Labor Complications
Pregnancy Complications
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Gonadal Disorders
Endocrine System Diseases
Lenograstim
Sargramostim
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs