Premature Ovarian Failure (POF)Phase 4ASCOT-2NCT03535480
Autologous Bone Marrow Stem Cell Ovarian Transplantation to Restore Ovarian Function in Premature Ovarian Failure
A Phase 4 study testing G-CSF and ASCOT in people with Premature Ovarian Failure (POF), run by Instituto de Investigacion Sanitaria La Fe at 1 site in Spain.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 38 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Premature Ovarian Failure (POF)
- What is being tested?
- G-CSF and ASCOT
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteSpain
- Study dates
- Jun 2018to Jun 2022
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 38 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- ≤ 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.
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
Spain1 site
Hospital Universitario y Politécnico la Fe-IIS la Fe
Valencia, 46026
Sonia Herraiz, PhD
Nuria Pellicer de Castellví, Doctor
About this study
Official title: Autologous Stem Cell Ovarian Transplantation to Restore Ovarian Function in Premature Ovarian Failure Patients. Pilot Study ASCOT-2
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.
Read the 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.
- Conditions
- Premature Ovarian Failure (POF)
- Being tested
- G-CSF, ASCOT
- Keywords
- ovarian reserve
- Medical subject headings
- Primary Ovarian Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
G-CSFDrug
Also called Granulocyte colony stimulating factor
G-CSF subcutaneously during five days
ASCOTCombination product
G-CSF subcutaneously during five days, aphaeresis to hematopoietic stem cell collection and catheterism for ovarian artery infusion
| Study group | Role | What they receive |
|---|---|---|
| G-CSF | Experimental | Only receives G-CSF subcutaneously five days for stem cell mobilization Receives: Drug: G-CSF |
| ASCOT | Experimental | Receives G-CSF subcutaneously five days and then plasmapheresis for hematopoietic stem cell collection and catheterism for infusion in ovarian artery Receives: Drug: G-CSF; Combination Product: ASCOT |
What is being measured
The primary outcome is the main question the study is designed to answer.
Antral follicle count (AFC)
every antral follicle is measured
Measured: 6 months
Secondary outcomes (7)
Time to Menses recovery
Spontaneous menstrual cycle restoration and its characteristics
Measured: 6 months
serum follicle stimulating hormone (FSH) and estradiol
serum extraction for biological measurements
Measured: 6 months
ovarian reserve dynamics
ultrasound observation of follicular development
Measured: 6 months
Controlled Ovarian Hyperstimulation (COH) response
ovarian response to gonadotropins
Measured: 6 months
pregnancy rate
pregnancy rate spontaneous and after COH
Measured: 2 years
Number of good quality embryos
Morphological criteria and developmental potential
Measured: 6 months
Number of participants with treatment-related adverse events
Secondary effects of the received interventions following hematological and gynecological medical criteria
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 May 2018
- Study startJun 2018 (estimated)
- Primary completionJun 2020 (estimated)
- Study completionJun 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Premature Ovarian Failure (POF)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Investigator
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Instituto de Investigacion Sanitaria La Fe
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Antonio Pellicer, Instituto de Investigacion Sanitaria La Fe
- Investigators
- Antonio Pellicer, Professor, Principal investigator, IIS la Fe
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03535480
- Sponsor's protocol ID
- 2017/0251
- Acronym
- ASCOT-2
- Status last verified
- May 2018
- First submitted
- 2 May 2018
- Last updated
- 24 May 2018
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 May 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Autologous Stem Cell Ovarian Transplantation to Restore Ovarian Function in Premature Ovarian Failure Patients. Pilot Study ASCOT-2
- ClinicalTrials.gov ID
- NCT03535480
- Acronym / sponsor ID
- ASCOT-2 / 2017/0251
- Conditions
- Premature Ovarian Failure (POF)
- Keywords
- ovarian reserve
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Instituto de Investigacion Sanitaria La FeUniversity, hospital or other
- Study start
- Jun 2018 (estimated)
- Primary completion
- Jun 2020 (estimated)
- Study completion
- Jun 2022 (estimated)
- First posted
- 24 May 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| G-CSF | Experimental | Drug: G-CSFOnly receives G-CSF subcutaneously five days for stem cell mobilization |
| ASCOT | Experimental | Drug: G-CSF, Combination Product: ASCOTReceives G-CSF subcutaneously five days and then plasmapheresis for hematopoietic stem cell collection and catheterism for infusion in ovarian artery |
Who may qualify
- Ages
- 18 to 38 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- ≤ 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.
Key exclusion criteria (8 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| G-CSFAlso: Granulocyte colony stimulating factorG-CSF subcutaneously during five days | Drug | ASCOT, G-CSF |
| ASCOTG-CSF subcutaneously during five days, aphaeresis to hematopoietic stem cell collection and catheterism for ovarian artery infusion | Combination product | ASCOT |
Primary outcome
Antral follicle count (AFC)
Time frame: 6 months
every antral follicle is measured
7 secondary outcomes
Time to Menses recovery
Time frame: 6 months
serum follicle stimulating hormone (FSH) and estradiol
Time frame: 6 months
ovarian reserve dynamics
Time frame: 6 months
Controlled Ovarian Hyperstimulation (COH) response
Time frame: 6 months
pregnancy rate
Time frame: 2 years
Number of good quality embryos
Time frame: 6 months
Number of participants with treatment-related adverse events
Time frame: 6 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 May 2018.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Antonio Pellicer, Professor principal investigator
IIS la Fe
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing G-CSF and ASCOT in people with Premature Ovarian Failure (POF), run by Instituto de Investigacion Sanitaria La Fe at 1 site in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 24 May 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Monica Romeu, Doctor (+34961244000 ext. 244116, monicaromeuvillarroya@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Antral follicle count (AFC) (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 May 2018.