Intra-ovarian Injection of MSC-EVs in Idiopathic Premature Ovarian Failure

NCT06202547 | Unknown Phase 1 DMC

• 2 other identifiers: 400000134IRCT20080831001141N43
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

Premature ovarian failure (POF) is a clinical syndrome defined by loss of ovarian activity before the age of 40 years. POF is characterized by menstrual disturbance (amenorrhea or oligomenorrhea) with raised gonadotrophins and low estradiol. The prevalence of POF is 1-2%. Extracellular vesicles (EVs) are membrane-packed vesicles that are secreted by a variety of cell types, including T cells, B cells, dendritic cells, platelets, mast cells, epithelial cells, endothelial cells, neuronal cells, cancerous cells, oligodendrocytes, Schwann cells, embryonic cells, and mesenchymal stromal cells-derived (MSCs). MSCs-EV more stable and induce stronger signaling and are produced in higher concentrations than stem cells. They demonstrate no inherent toxicity, are not associated with any long-term maldifferentiation of engrafted cells or tumor generation, and carry no apparent risk of aneuploidy or immune rejection following in vivo allogenic administration.Several studies have evaluated the safety and possible efficacy of injection MSCs-EV for the treatment of premature ovarian failure in animal models. Based on the available evidence, the study was designed with the aim of investigating the safety and effectiveness of intraovarian injection of MSCs-EV in patients with POF diagnosis.

Conditions

Premature Ovarian Failure

Keywords

Intra-ovarian injection; Mesenchymal stromal cells-derived extracellular vesicles

Outcome Measures

Primary Outcomes (1)

• Rate of ovary abscess

  Sonographic evaluation of ovaries will be done for detection of ovarian abscess or any other ovarian lesion formation up to 8 months after intraovarian injection of extracellular vesicles derived from bone marrow mesenchymal stromal cells (any adverse events through follow-up visits (first 24 hours and first week after transplantation, 1, 2, 3, 4, 5, 6, 7 and 8 months after injection) will be checked and recorded.

  First 24 hours, first week and monthly up to 8 months after injection

Secondary Outcomes (5)

• Basal follicle-stimulating hormone (FSH) serum level

  Baseline,1 week as well as one, two, three, four , five, six, seven and eight months after transplantation

• Serum anti-mullerian hormone (AMH) levels

  Before the intervention (baseline) and also three, six and eight months after transplantation

• Menstruation recurrence rate

  one, two, three, four , five, six, seven and eight months after transplantation

• Antral follicle count

  Before the intervention (baseline) as well as one, two, three, four , five, six, seven and eight months after transplantation

• The ovaries size and volume

  One, two, three, four , five, six, seven and eight months after transplantation

Study Arms (1)

intraovarian injection of MSC-EVs

EXPERIMENTAL

The patient is anesthetized and placed in a lithotomy position, after preparing and washing the vagina with normal saline, under transvaginal ultrasound guidance (Aloka-40000 vaginal probe, Japan) using needle puncture (Reproline medical Gmbh, Rheinbach/Germany). The injection of 2 ml of extracellular vesicles derived from MSCs (equivalent to 30 million cells) will be performed into one ovary of the patient (the accessible ovary).

Biological: Intra-ovarian injection of bone marrow mesenchymal stromal cells-derived extracellular vesicles

Interventions

Intra-ovarian injection of bone marrow mesenchymal stromal cells-derived extracellular vesicles BIOLOGICAL

he patient is anesthetized and placed in a lithotomy position, after preparing and washing the vagina with normal saline, under transvaginal ultrasound guidance (Aloka-40000 vaginal probe, Japan) using needle puncture (Reproline medical Gmbh, Rheinbach/Germany). The injection of 2 ml of extracellular vesicles derived from MSCs (equivalent to 30 million cells) will be performed into one ovary of the patient (the accessible ovary).

intraovarian injection of MSC-EVs

Eligibility Criteria

• Age: 20 Years - 38 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Women between 20-38 years old
• Baseline serum level of follicle stimulating hormone (FSH) higher or equal to 25 IU/l at least twice with an interval of 3 or 4 months
• At least one year has passed since secondary amenorrhea and premature ovarian failure (POF) diagnosis
• Normal karyotype and fragile X messenger ribonucleoprotein 1 (FMR1) gene

You may not qualify if:

• Primary amenorrhea
• Congenital anomaly of the ovary
• Thyroid disease Immune system diseases such as lupus, etc.
• Previous and/or family history of ovarian tumor
• Previous and/or family history of suffering from major diseases in the past and present such as cancer
• Positive serological evidence regarding previous or current hepatitis B and C, Human T-lymphotropic virus 1, Human immunodeficiency virus (HIV), Syphilis Disturbance in the normal range of laboratory tests as levels of Hemoglobin Subunit Alpha 1 (HbA1), Alanine transaminase (ALT), The aspartate aminotransferase (AST), the number of white blood cells (WBCs), The creatinine (Cr), International normalised ratio (INR) , Platelets (Plt), Hematocrit (Hct) tests.
• History of specific systemic disease (rheumatology, endocrine, cardiovascular, etc.)
• Severe endometriosis (stage III and IV)
• Small and non-injectable ovaries Lack of patient satisfaction
• The patient's unwillingness to continue participating in the study

Sponsors & Collaborators

• Royan Institute: lead

Study Sites (1)

Royan Institute

Tehran, Iran

RECRUITING

MeSH Terms

Conditions

Primary Ovarian Insufficiency

Condition Hierarchy (Ancestors)

Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Gonadal Disorders; Endocrine System Diseases

Study Officials

• Faezeh Shekari, Ph.D

  Department of Development of Stem Cell Sciences of Royan Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Parvaneh Afsharian, Ph.D

CONTACT

+9802123562674; p.afsharian@royan-rc.ac.ir

Mehri Mashayekhi, M.D

CONTACT

+9809123250933; dr.mashayekhy@yahoo.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 5, 2023
• First Posted: January 11, 2024
• Study Start: February 20, 2023
• Primary Completion: September 20, 2024
• Study Completion: February 18, 2025
• Last Updated: January 11, 2024

Record last verified: 2024-01

Locations

IR (1)