Stem Cell Therapy and Growth Factor Ovarian in Vitro Activation (SEGOVA)

August 5, 2020 updated by: Forever Young d.o.o.

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Anticipated)

100

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Malta
      • Sliema, Malta, SLM 3011
        • Saint James Hospital Malta
  • North Macedonia
    • Macedonia
      • Skopje, Macedonia, North Macedonia, 1000
        • Re-medika Hospital
  • Serbia
      • Belgrade, Serbia, 11000
        • Medigroup Health System, Jevremova hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

23 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

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

Exclusion Criteria:

  • 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
  • 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).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: SEGOVA Intervention Group
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.
Combination product: SEGOVA procedure
SEGOVA procedure includes - Stem cell therapy, G - Growth factor Platelet Plasma Rich therapy and in Vitro Activation of the ovaries.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Oocyte presence
Time Frame: 12 months
The numbers of oocytes retrieved after the treatment would be monitored during sonographic follow-ups .
12 months
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.
12 months
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.
12
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.
12
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.
6

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Fertilization and implantation rate
Time Frame: 12 months
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.
12 months
Number of participants with Positive Clinical Pregnancy
Time Frame: 24 months
Following completion of trial procedure, patients will be monitored for ongoing clinical pregnancies and conceptions, at the site or via post-treatment correspondence.
24 months
Changes in total score of The World Health Organization Quality of Life (WHOQOL) BREF modified scale
Time Frame: 12 months
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.
12 months
Changes in anti-Mullerian hormone (AMH) levels (ng/mL)
Time Frame: 6 months
Changes in AMH levels would be monitored during one year follow-up procedure and compared to the pre-procedure levels.
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Forever Young d.o.o.

Collaborators

Medigroup Health System, Jevremova hospital
Saint James Hospital Malta
Re-medika Hospital Skoplje

Investigators

  • Principal Investigator: Aleksandar Ljubic, MD, PhD, Medigroup, Belgrade, Serbia

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 1, 2019

Primary Completion (Anticipated)

December 1, 2020

Study Completion (Anticipated)

December 1, 2021

Study Registration Dates

First Submitted

June 29, 2019

First Submitted That Met QC Criteria

July 3, 2019

First Posted (Actual)

July 5, 2019

Study Record Updates

Last Update Posted (Actual)

August 6, 2020

Last Update Submitted That Met QC Criteria

August 5, 2020

Last Verified

August 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IRB No 63/295/2015

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

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.

IPD Sharing Time Frame

Draft study protocol and Statistical Analysis Plan are available entire duration of the study. Informed Consent Forms would be available upon study completion date.

IPD Sharing Access Criteria

Access to any additional supporting information about the protocol description or methods used to collect the data will be shared if required by other research organisations. Request would be reviewed by Principal Investigator.

IPD Sharing Supporting Information Type

  • Study Protocol
  • Statistical Analysis Plan (SAP)
  • Informed Consent Form (ICF)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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