Protocol summary
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Study aim
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Investigating the effect of intraovarian injection of bone marrow-derived extracellular vesicles (MSC-EV) on serum levels of Follicle-Stimulating Hormone (FSH),Anti-Mullerian Hormone (AMH) levels, as well as the return of the menstrual cycle in infertile patients with premature ovarian failure, as well as the evaluation of its possible side effects.
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Design
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A before/after clinical trial (phase I) on 10 patients
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Settings and conduct
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For all patients in the infertility clinic of Royan Research Institute, first a basic visit will be done to obtain basic laboratory data, hormone levels and ultrasound examination of the ovaries, and then MSC-EV will be injected into the ovaries with a determined dose.
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Participants/Inclusion and exclusion criteria
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Infertile women who have been diagnosed with premature ovarian failure and have normal body mass index and normal genetic tests are invited to participate in this project. Patients with early amenorrhea and certain immunological and cardiovascular diseases, as well as a history of ovarian masses or abnormal serological tests will not be included in the study. If the patient has undergone hormone replacement therapy (HRT), the HRT will be stopped for at least two months and then the injection cycle will be started.
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Intervention groups
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Injection of bone marrow-derived extracellular vesicles with a dose equivalent to 3 times 10 million clonal mesenchymal stem cells in 2 ml will be performed for all patients.
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Main outcome variables
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Follow-up of patients in order to respond to treatment for 8 months based on evaluation of Follicle-Stimulating Hormone (FSH),Anti-Mullerian Hormone (AMH) levels, return of menstrual cycle, ovarian ultrasound and also check possible complications due to injection (fever, bacteremia, sepsis, Pelvic inflammatory disease, anaphylactic shock and hematoma from the first 24 hours and in the first week) will be done.
General information
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Reason for update
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Completion of the trial recruitment and follow-up process
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Acronym
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IRCT registration information
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IRCT registration number:
IRCT20080831001141N43
Registration date:
2023-10-17, 1402/07/25
Registration timing:
registered_while_recruiting
Last update:
2026-06-10, 1405/03/20
Update count:
2
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Registration date
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2023-10-17, 1402/07/25
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Registrant information
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Recruitment status
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Recruitment complete
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Funding source
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Expected recruitment start date
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2023-02-20, 1401/12/01
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Expected recruitment end date
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2025-02-18, 1403/11/30
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Actual recruitment start date
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2023-02-20, 1401/12/01
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Actual recruitment end date
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2024-10-08, 1403/07/17
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Trial completion date
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2025-07-08, 1404/04/17
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Scientific title
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Safety and feasibility study of intra-ovarian injection of bone marrow mesenchymal stromal cells-derived extracellular vesicles in idiopathic premature ovarian failure patients: Clinical trial phase I
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Public title
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Investigating the effect of intraovarian injection of extracellular vesicles derived from bone marrow mesenchymal stromal cells in patients with premature ovarian failure.
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Purpose
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Treatment
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Inclusion/Exclusion criteria
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Inclusion criteria:
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
Exclusion criteria:
Primary amenorrhea
Congenital anomaly of the ovary
Thyroid disease
Immune system diseases such as lupus and...
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 plan
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Age
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From 20 years old to 38 years old
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Gender
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Female
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Phase
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1
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Groups that have been masked
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No information
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Sample size
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Target sample size:
10
Actual sample size reached:
10
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Randomization (investigator's opinion)
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N/A
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Randomization description
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Blinding (investigator's opinion)
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Not blinded
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Blinding description
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Placebo
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Not used
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Assignment
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Single
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Other design features
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Ethics committees
1
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Ethics committee
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Approval date
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2022-01-04, 1400/10/14
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Ethics committee reference number
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IR.ACECR.ROYAN.REC.1400.124
Health conditions studied
1
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Description of health condition studied
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Premature ovarian failure
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ICD-10 code
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E28.3
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ICD-10 code description
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Primary ovarian failure
Primary outcomes
1
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Description
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Ovary abscess
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Timepoint
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First 24 hours, first week and monthly up to 8 months after injection
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Method of measurement
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Evaluation 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.
Secondary outcomes
1
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Description
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Basal follicle-stimulating hormone (FSH) serum level
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Timepoint
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Baseline,1 week as well as one, two, three, four , five, six, seven and eight months after transplantation
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Method of measurement
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Laboratory test
2
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Description
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Serum anti-mullerian hormone (AMH) levels
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Timepoint
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Before the intervention (baseline) and also three, six and eight months after transplantation
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Method of measurement
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Laboratory test
3
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Description
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Menstruation recurrence rate
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Timepoint
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one, two, three, four , five, six, seven and eight months after transplantation
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Method of measurement
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Through monthly follow-up and asking the questions
Intervention groups
1
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Description
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Intervention group: 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 50 million cells) will be performed into one ovary of the patient (the accessible ovary).
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Category
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Treatment - Other
1
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Sponsor
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Grant name
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Grant code / Reference number
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Is the source of funding the same sponsor organization/entity?
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Yes
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Title of funding source
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Lotus Royan Charitable Fundation
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Proportion provided by this source
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25
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Public or private sector
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Private
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Domestic or foreign origin
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Domestic
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Category of foreign source of funding
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empty
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Country of origin
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Type of organization providing the funding
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Other
2
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Sponsor
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Grant name
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Grant code / Reference number
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Is the source of funding the same sponsor organization/entity?
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Yes
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Title of funding source
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Vice Presidency for Science and Technology’s Department of Development of Stem Cell Sciences
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Proportion provided by this source
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75
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Public or private sector
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Public
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Domestic or foreign origin
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Domestic
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Category of foreign source of funding
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empty
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Country of origin
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Type of organization providing the funding
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Academic
Sharing plan
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Deidentified Individual Participant Data Set (IPD)
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Yes - There is a plan to make this available
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Study Protocol
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Undecided - It is not yet known if there will be a plan to make this available
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Statistical Analysis Plan
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Undecided - It is not yet known if there will be a plan to make this available
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Informed Consent Form
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Yes - There is a plan to make this available
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Clinical Study Report
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Yes - There is a plan to make this available
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Analytic Code
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Undecided - It is not yet known if there will be a plan to make this available
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Data Dictionary
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Undecided - It is not yet known if there will be a plan to make this available
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Title and more details about the data/document
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Information regarding main consequence
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When the data will become available and for how long
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6 months after paper publication
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To whom data/document is available
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Researchers in academic institutes
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Under which criteria data/document could be used
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Systematic review and meta-analysis articles
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From where data/document is obtainable
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The scientific principal of the project whose information is registered on the site.
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What processes are involved for a request to access data/document
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Sending request to principle investigator
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Comments
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