MenopausePhase 1/2SEGOVANCT04009473
Stem Cell Therapy and Growth Factor Ovarian in Vitro Activation
A Phase 1/2 study testing SEGOVA procedure in people with Menopause and Menopause Ovarian Failure, run by Forever Young d.o.o. at 3 sites in 3 countries.
Trial summary
SEGOVA procedure includes - Stem cell therapy, G - Growth factor Platelet Plasma Rich therapy and in Vitro Activation of the ovaries. Read more about this study
- Who is it for?
- Ages 25 years and older, women only
- Conditions the study is for
- Menopause, Menopause Ovarian Failure, Ovarian Failure
- What is being tested?
- SEGOVA procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 3 sitesin 3 countries
- Study dates
- 1 Jun 2019to Dec 2021
- Phase
- Phase 1/2
- 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 25 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Confirmed informed consent, signature and date
- A woman over 25 years of age
- Primary or secondary amenorrhea for at least 3 months
- Hormone Anti Mullerian Hormone values <_0.42 ng / ML and Follicle stimulating hormone FSH> 20 IU / L, and / or failure of previous attempts of assisted reproductive techniques due to limited ovarian response (less than 3 oocyte cells obtained).
- The proper karyotype 46, XX.
- Presence of at least one ovary
Who cannot join
- Currently pregnancy or breastfeeding
- Presence of Sexually Transmitted Disease (STD positive)
- There is presence of acute infection (C Reactive Protein>5)
- There is an anamnesis or evidence of existing gynecological malignancy
- The presence of adnexal masses indicating the need for further evaluation.
- It has a contraindication to laparoscopic surgery and / or general anesthesia
Show all 9Show fewer
- Over the past two weeks, use of the following medicines: Oral or systemic corticosteroids, hormones (estrogen, progestins, oral contraceptives), Danazol, anticoagulants, herbal or botanical supplements with potential hormonal effects.
- Type I diabetes mellitus
- Known significant anemia (hemoglobin <8 g / dL), Severe venous thrombosis and / or pulmonary embolism, Cerebrovascular disease, Presence of heart disease, Premature kidney disease (defined as urea in the blood> 30 mg / dL or serum creatinine> 1.6 mg / dL).
Trial locations and contacts
3 sites in 3 countries.
3 sites in 3 countries
About this study
Official title: Platelet Rich Plasma Ovarian in Vitro Activation and Stem Cells Transplantation In Women With Ovarian Failure
SEGOVA procedure includes - Stem cell therapy, G - Growth factor Platelet Plasma Rich therapy and in Vitro Activation of the ovaries.
Read the detailed description
The current study seeks to demonstrate how integrative ovarian rejuvenation program called SEGOVA influence the restoration of hormone stability and increase in the number of follicles in ovarian failure patients. The recruitment of patients and data collection would be performed at three sites: The Special Hospital Jevremova Belgrade, Saint James Hospital Malta, and Remedica Skopje Hospital, Macedonia. A 50-100 of Infertile women with ovarian failure will be included in the period between July 2019 - December 2021. The patients would be coded when entering the program, and all personal information would be protected. Information about medical treatment and background will be held on both paper and electronic case report forms.The result of the procedure will be maintained in the research database with blinding to clinical physician that will perform post procedure follow-up of those patients. In case of a complication, possibly related to treatment, the case will be unblinded.
The first day of procedure, autologous platelet rich plasma (PRP) is obtained from 100-120 mL of whole blood. After separation 4 mL of PRP is obtained. Concentration of platelets is optimised on 6-8x baseline and 2-3x leucocytes baseline. For activation of PRP autologous thrombin is used in ratio 1:10.
On the same day the laparoscopic cortical resection of the ovary is performed in standard technique. Ovarian cortex sample is minced in a petri dish.The volume of activated PRP (4 mL) is mixed with ovarian fragments and incubated for the next 48h at 37℃ and 5% CO2. After 48h, the bone marrow sampling from tibia under general anesthesia is performed to obtain bone marrow. After centrifugation the Bone Marrow Aspirate Concentrate (BMAC) with nucleated cells is obtained (3 +/- 1,5 mL).
Finally, after the 48h has passed from ovarian cortex tissue incubation, fragmented tissue of the ovary with 4 mL of PRP will be injected together with 3 +/- 1.5 mL BMAC into the subcortical region of the both ovaries as transvaginal ultra sound guided injection.
After the procedure, during one year follow up, hormone levels of follicle stimulating hormone (FSH), luteinizing hormone (LH),estradiol (E2), progesterone (PG) and anti-mullerian hormone (AMH) would be measured and the follicle numbers would be monitored to provide insight regarding the ovarian function.To investigate the changes in hormone levels, comparisons of the levels detected prior to the intervention, and 3, 6 and 12 months post-intervention, would be performed using Wilcoxon's rank test. Descriptive statistics will be provided for each variable as mean or median number, frequency, percentage, table or graph.
In patients with oocytes retrieved after SEGOVA procedure, standard In Vitro Fertilization protocol would be performed,and fertilization, cleavage and clinical pregnancy rates will be monitored.
- Conditions
- Menopause, Menopause Ovarian Failure, Ovarian Failure, Premature Ovarian Failure, Premature Ovarian Failure 1, Premature Ovarian Failure 2A
- Being tested
- SEGOVA procedure
- Keywords
- platelet rich plasma, growth factors, stem cells, bone marrow, in vitro activation, ovarian cortex transplantation, hippo signalling pathway
- Medical subject headings
- Primary Ovarian Insufficiency, Premature Ovarian Failure 2a, Premature Ovarian Failure 2b, Premature Ovarian Failure 3, Ovarian Dysgenesis 2, Premature Ovarian Failure 5, Premature Ovarian Failure 6, Premature Ovarian Failure 7
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SEGOVA procedureCombination product
SEGOVA procedure includes - Stem cell therapy, G - Growth factor Platelet Plasma Rich therapy and in Vitro Activation of the ovaries.
| Study group | Role | What they receive |
|---|---|---|
| SEGOVA Intervention Group | Experimental | Intervention group of 50-100 patients with ovarian failure would be subjected to a three-day procedure named SEGOVA: bone marrow derived StEm cell treatment, Growth factor incubation and Ovarian In Vitro Activation. After the procedure, one year follow up of hormones measurements (follicle stimulating hormone (FSH), luteinizing hormone (LH),estradiol (E2), progesterone (PG) and anti-mullerian hormone (AMH)) and follicle counts would be established. In patients with oocytes retrieved after SEGOVA procedure, standard In Vitro Fertilization protocol would be performed. The fertilization, cleavage and clinical pregnancy rate will be monitored. Receives: Combination Product: SEGOVA procedure |
What is being measured
The primary outcome is the main question the study is designed to answer.
Oocyte presence
The numbers of oocytes retrieved after the treatment would be monitored during sonographic follow-ups .
Measured: 12 months
Changes in Hormone Levels of Follicle-stimulating hormone FSH (mIU/mL)
Changes in hormonal levels of FSH toward normal ranges would be monitored during one year follow-up procedure.
Measured: 12 months
Changes in Hormone Levels of Luteinizing Hormone (mIU/mL)
Changes in hormonal levels of LH toward normal ranges would be monitored during one year follow-up procedure.
Measured: 12
Changes in Hormone Levels of Estradiol E2 (pg/mL)
Changes in hormonal levels of E2 toward normal ranges would be monitored during one year follow-up procedure.
Measured: 12
Changes in Hormone Levels of Progesterone PG (ng/mL)
Changes in hormonal levels of PG toward normal ranges would be monitored during one year follow-up procedure.
Measured: 6
Secondary outcomes (4)
Fertilization and implantation rate
Following the Ovarian Rejuvenation Treatment, subjects with oocytes retrieved will undergo IVF protocol, and fertilization and cleavage of embryo would be monitored to evaluate fertility outcomes after SEGOVA procedure.
Measured: 12 months
Number of participants with Positive Clinical Pregnancy
Following completion of trial procedure, patients will be monitored for ongoing clinical pregnancies and conceptions, at the site or via post-treatment correspondence.
Measured: 24 months
Changes in total score of The World Health Organization Quality of Life (WHOQOL) BREF modified scale
Change in quality of life total score for each participant post-procedure would be examined and compared to pre-procedure status. The WHOQOL bref questionnaire would be used as a self-report measure of functional health and well-being. Original WHOQOL bref scale uses 26 questions, while our modified version was abbreviated to 18 questions. The WHOQOL-BREF is scored using a Likert scale, with patients choosing to express how much they agree or disagree with a particular statement from 1 to 5 on a response scale. The value 5 indicates they strongly agree, while 1 is disagree. Total score would be obtained as the sum of 18 questions values from 1 to 5, giving minimum value of total score 18, and a maximum score 90.
Measured: 12 months
Changes in anti-Mullerian hormone (AMH) levels (ng/mL)
Changes in AMH levels would be monitored during one year follow-up procedure and compared to the pre-procedure levels.
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 posted5 Jul 2019
- Study start1 Jun 2019
- Primary completionDec 2020 (estimated)
- Study completionDec 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for MenopauseStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Pre-post study design: A study group receives the intervention, and the changes in parameters were measured and compared before and after the intervention.
- Masking
- None (open label)
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Forever Young d.o.o.
- Sponsor type
- University, hospital or other
- Collaborators
- Medigroup Health System, Jevremova hospital, Saint James Hospital Malta, Re-medika Hospital Skoplje
- Responsible party
- Sponsor
- Investigators
- Aleksandar Ljubic, MD, PhD, Principal investigator, Medigroup, Belgrade, Serbia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04009473
- Sponsor's protocol ID
- IRB No 63/295/2015
- Acronym
- SEGOVA
- Status last verified
- Aug 2020
- First submitted
- 29 Jun 2019
- Last updated
- 6 Aug 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- Yes: the individual participant data would be available considering Draft Study Protocol, Statistical analysis Plan, and Informed Consent Forms, and also the data that are published related to this study.
Publications
Tinjic S, Abazovic D, Ljubic D, Vojvodic D, Bozanovic T, Ibrisimovic M, Markovic S, Ljubic A. Influence of Autologous In Vitro Activation of Ovaries by Stem Cells and Growth Factors on Endocrine and Reproductive Function of Patients with Ovarian Insufficiency-A Clinical Trial Study. Int J Fertil Steril. 2021 Jul;15(3):178-188. doi: 10.22074/IJFS.2020.134678. Epub 2021 Jun 22.
PubMed 34155864
Study at a glance
From the registry record, last updated by the sponsor on 6 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Platelet Rich Plasma Ovarian in Vitro Activation and Stem Cells Transplantation In Women With Ovarian Failure
- ClinicalTrials.gov ID
- NCT04009473
- Acronym / sponsor ID
- SEGOVA / IRB No 63/295/2015
- Conditions
- Menopause, Menopause Ovarian Failure, Ovarian Failure, Premature Ovarian Failure, Premature Ovarian Failure 1, Premature Ovarian Failure 2A
- Keywords
- platelet rich plasma, growth factors, stem cells, bone marrow, in vitro activation, ovarian cortex transplantation, hippo signalling pathway
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Forever Young d.o.o.University, hospital or other
- Collaborators
- Medigroup Health System, Jevremova hospital, Saint James Hospital Malta, Re-medika Hospital Skoplje
- Study start
- 1 Jun 2019 (actual)
- Primary completion
- Dec 2020 (estimated)
- Study completion
- Dec 2021 (estimated)
- First posted
- 5 Jul 2019 (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.
SEGOVA procedure includes - Stem cell therapy, G - Growth factor Platelet Plasma Rich therapy and in Vitro Activation of the ovaries.
Detailed description
The current study seeks to demonstrate how integrative ovarian rejuvenation program called SEGOVA influence the restoration of hormone stability and increase in the number of follicles in ovarian failure patients. The recruitment of patients and data collection would be performed at three sites: The Special Hospital Jevremova Belgrade, Saint James Hospital Malta, and Remedica Skopje Hospital, Macedonia. A 50-100 of Infertile women with ovarian failure will be included in the period between July 2019 - December 2021. The patients would be coded when entering the program, and all personal information would be protected. Information about medical treatment and background will be held on both paper and electronic case report forms.The result of the procedure will be maintained in the research database with blinding to clinical physician that will perform post procedure follow-up of those patients. In case of a complication, possibly related to treatment, the case will be unblinded.
The first day of procedure, autologous platelet rich plasma (PRP) is obtained from 100-120 mL of whole blood. After separation 4 mL of PRP is obtained. Concentration of platelets is optimised on 6-8x baseline and 2-3x leucocytes baseline. For activation of PRP autologous thrombin is used in ratio 1:10.
On the same day the laparoscopic cortical resection of the ovary is performed in standard technique. Ovarian cortex sample is minced in a petri dish.The volume of activated PRP (4 mL) is mixed with ovarian fragments and incubated for the next 48h at 37℃ and 5% CO2. After 48h, the bone marrow sampling from tibia under general anesthesia is performed to obtain bone marrow. After centrifugation the Bone Marrow Aspirate Concentrate (BMAC) with nucleated cells is obtained (3 +/- 1,5 mL).
Finally, after the 48h has passed from ovarian cortex tissue incubation, fragmented tissue of the ovary with 4 mL of PRP will be injected together with 3 +/- 1.5 mL BMAC into the subcortical region of the both ovaries as transvaginal ultra sound guided injection.
After the procedure, during one year follow up, hormone levels of follicle stimulating hormone (FSH), luteinizing hormone (LH),estradiol (E2), progesterone (PG) and anti-mullerian hormone (AMH) would be measured and the follicle numbers would be monitored to provide insight regarding the ovarian function.To investigate the changes in hormone levels, comparisons of the levels detected prior to the intervention, and 3, 6 and 12 months post-intervention, would be performed using Wilcoxon's rank test. Descriptive statistics will be provided for each variable as mean or median number, frequency, percentage, table or graph.
In patients with oocytes retrieved after SEGOVA procedure, standard In Vitro Fertilization protocol would be performed,and fertilization, cleavage and clinical pregnancy rates will be monitored.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Pre-post study design: A study group receives the intervention, and the changes in parameters were measured and compared before and after the intervention.
| Arm | Type | Receives |
|---|---|---|
| SEGOVA Intervention Group | Experimental | Combination Product: SEGOVA procedureIntervention group of 50-100 patients with ovarian failure would be subjected to a three-day procedure named SEGOVA: bone marrow derived StEm cell treatment, Growth factor incubation and Ovarian In Vitro Activation. After the procedure, one year follow up of hormones measurements (follicle stimulating hormone (FSH), luteinizing hormone (LH),estradiol (E2), progesterone (PG) and anti-mullerian hormone (AMH)) and follicle counts would be established. In patients with oocytes retrieved after SEGOVA procedure, standard In Vitro Fertilization protocol would be performed. The fertilization, cleavage and clinical pregnancy rate will be monitored. |
Who may qualify
- Ages
- 25 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Confirmed informed consent, signature and date
- A woman over 25 years of age
- Primary or secondary amenorrhea for at least 3 months
- Hormone Anti Mullerian Hormone values <_0.42 ng / ML and Follicle stimulating hormone FSH> 20 IU / L, and / or failure of previous attempts of assisted reproductive techniques due to limited ovarian response (less than 3 oocyte cells obtained).
- The proper karyotype 46, XX.
Key exclusion criteria (9 listed)
- Currently pregnancy or breastfeeding
- Presence of Sexually Transmitted Disease (STD positive)
- There is presence of acute infection (C Reactive Protein>5)
- There is an anamnesis or evidence of existing gynecological malignancy
- The presence of adnexal masses indicating the need for further evaluation.
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 |
|---|---|---|
| SEGOVA procedureSEGOVA procedure includes - Stem cell therapy, G - Growth factor Platelet Plasma Rich therapy and in Vitro Activation of the ovaries. | Combination product | SEGOVA Intervention Group |
Primary outcome
Oocyte presence
Time frame: 12 months
The numbers of oocytes retrieved after the treatment would be monitored during sonographic follow-ups .
Changes in Hormone Levels of Follicle-stimulating hormone FSH (mIU/mL)
Time frame: 12 months
Changes in hormonal levels of FSH toward normal ranges would be monitored during one year follow-up procedure.
Changes in Hormone Levels of Luteinizing Hormone (mIU/mL)
Time frame: 12
Changes in hormonal levels of LH toward normal ranges would be monitored during one year follow-up procedure.
Changes in Hormone Levels of Estradiol E2 (pg/mL)
Time frame: 12
Changes in hormonal levels of E2 toward normal ranges would be monitored during one year follow-up procedure.
Changes in Hormone Levels of Progesterone PG (ng/mL)
Time frame: 6
Changes in hormonal levels of PG toward normal ranges would be monitored during one year follow-up procedure.
4 secondary outcomes
Fertilization and implantation rate
Time frame: 12 months
Number of participants with Positive Clinical Pregnancy
Time frame: 24 months
Changes in total score of The World Health Organization Quality of Life (WHOQOL) BREF modified scale
Time frame: 12 months
Changes in anti-Mullerian hormone (AMH) levels (ng/mL)
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 6 Aug 2020.
- Derived from this study: PubMed 34155864Tinjic S, Abazovic D, Ljubic D, Vojvodic D, Bozanovic T, Ibrisimovic M, Markovic S, Ljubic A. Influence of Autologous In Vitro Activation of Ovaries by Stem Cells and Growth Factors on Endocrine and Reproductive Function of Patients with Ovarian Insufficiency-A Clinical Trial Study. Int J Fertil Steril. 2021 Jul;15(3):178-188. doi: 10.22074/IJFS.2020.134678. Epub 2021 Jun 22.
- Individual participant dataSharing planned: Yes. the individual participant data would be available considering Draft Study Protocol, Statistical analysis Plan, and Informed Consent Forms, and also the data that are published related to this study.
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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.
Aleksandar Ljubic, MD, PhD principal investigator
Medigroup, Belgrade, Serbia
3 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing SEGOVA procedure in people with Menopause and Menopause Ovarian Failure, run by Forever Young d.o.o. at 3 sites in 3 countries.
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 6 inclusion and 9 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 6 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Malta, North Macedonia, Serbia. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Oocyte presence (time frame: 12 months). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04009473, which also lists 1 linked publication.
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 6 Aug 2020.