Umbilical Cord Plasma for Treating Endometrial Pathologies (Thin Endometrium / Asherman's Syndrome/ Endometria Atrophy)

Asherman Syndrome Clinical Trial

— hSCU-PRP  

Official title:

Umbilical Cord Plasma for Treating Endometrial Pathologies (Thin Endometrium / Asherman's Syndrome/ Endometria Atrophy).

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05095597
• Other study ID #: 2001-FIVI-002-IC
• Secondary ID: 2020-005717-40
• Status: Recruiting
• Phase: Phase 2
• Start date: April 22, 2022
• Est. completion date: March 2025

Study information

• Verified date: February 2024
• Source: Fundación IVI
• Contact: Irene Cervelló Alcaráz, PhD.
• Phone: +34963903305
• Email: irene.cervello[@]ivirma.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

In the last years, platelet-rich plasma (PRP) has emerged as a promising alternative to treat endometrial pathologies affecting the endometrial lining. Different studies have tried this therapeutic approach in human patient, but results are not conclusive at all. Also, in the last years, different studies have suggested the umbilical cord blood has a stronger reservoir of growth factors and other pro-regenerative molecules than the adult peripheral blood. That is the reason why the present study aims to evaluate if using platelet-rich plasma obtained from umbilical cord blood is able to increase endometrial thickness and prepare the endometrium for an embryo transference. However, due to the novelty of this approach, the investigators have considered to include a 'proof of concept' group (women with premature ovarian insufficiency) to obtain a deeper understanding of the clinical value of this blood derivative.

Description:

Phase II clinical trial, designed as a pilot study, single-center and open-label, which aims to study the efficacy of platelet-rich plasma from umbilical cord after injection into a pathological endometrium (thin endometrium, Asherman's Syndrome, endometrial atrophy). This treatment will be applied to patients with the aforementioned endometrial pathologies (group B), as well as to patients with premature ovarian failure (group A), which will serve to study its clinical value in greater detail. Plasma samples as well as endometrial biopsies will be analyzed to try to understand what molecular events are triggered in the endometrial tissue after the application of the treatment under study.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 45
• Est. completion date: March 2025
• Est. primary completion date: February 2025
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 48 Years

Eligibility

UMBILICAL CORD DONORS Donors of umbilical cord blood will be women (and their partners, if applicable) who give birth to a live newborn(s) in the Gynecology and Obstetrics service of HUP La Fe; the same umbilical cord collection criteria will be followed as standardized in HUP La Fe for the donation of this biological product. GROUP A

Inclusion Criteria:

• Patient information sheet and signed informed consent.
• Female, acting voluntarily, aged between 18 and 48 years at the time of recruitment.
• BMI = 18 kg/m2 and = 35 kg/m2.
• Patients with premature ovarian failure (amenorrhea prior to 40 years of age and FSH > 40 IU/L).

Exclusion Criteria:

• Active genital infection proven at the time of recruitment; chronic endometritis.
• Known endometrial pathology.
• Psychological disorder that may hinder study follow-up.
• Positive results after viral safety analysis (HBsAg, HBcAb, HCV, HIV1, HIV2, syphilis).
• Presenting any syndrome or condition that, from the principal investigator's point of view, could pose a risk to the study or to the patient.
• Any significant clinical anomaly detected during the recruitment process; simultaneous participation in another clinical study that could affect the objectives of the present study or previous participation in this same study. GROUP B

Inclusion Criteria:

• Information and signed informed consent.
• female, acting voluntarily, aged between 18 and 48 years at the time of recruitment.
• body mass index (BMI): = 18 kg/m2 and = 35 kg/m2.
• Patients undergoing an assisted reproduction cycle.
• Endometrial thickness < 5mm despite estrogen administration for more than 10 days and/or evidence of Asherman's Syndrome.

Exclusion Criteria:

• Active genital infection proven at the time of recruitment; chronic endometritis.
• Known endometrial pathology.
• Psychological disorder that may hinder study follow-up.
• Positive results after viral safety analysis (HBsAg, HBcAb, HCV, HIV1, HIV2, syphilis).
• Presenting any syndrome or condition that, from the principal investigator's point of view, could pose a risk to the study or to the patient.
• Any significant clinical anomaly detected during the recruitment process; simultaneous participation in another clinical study that could affect the objectives of the present study or previous participation in this same study.

Related Conditions & MeSH terms

• Asherman Syndrome
• Atrophy
• Endometrial Atrophy
• Syndrome

Intervention

Procedure:
• Injection of hUC-PRP by hysteroscopy
PRP previously frozen at -80ºC (6±2 mL) will be defrozen after checking donor-receptor compatibility and viral safety study. PRP (4±2 mL) will be activated with 5% CaCl2 and immediately injected (4±2 mL) in the sub-endometrial wall via hysteroscopy.

Drug:
• Oestraclin
Patients will receive estrogenic therapy, based on estradiol, for 10±2 days (oestraclin, topical cream, 5µg daily for 10±2 days).

Procedure:
• Umbilical cord blood collection
The SCU will be collected using a blood collection bag containing anticoagulant. This step will be performed by the medical and nursing staff of the obstetrics service of the HUP La Fe. The blood collection bags will be the following, or similar: Cord Blood Collection Bags from MACOPHARMA; CPD Umbilical Cord Bag from GRIFOLS.
• Endometrial biopsy
Biopsies will be taken by specialized medical personnel by aspiration with an intrauterine cannula (pipelle or cornier). Samples will be collected in 15 mL tubes (or in a larger capacity container if needed) containing PBS or RNA later until frozen at -80ºC, at the IVI Foundation facilities. Prior to freezing (in a 1.8-2 mL cryotube) the PBS will be removed and the sample cleaned in a Petri dish if needed.

Locations

Country	Name	City	State
Spain	Hospital la Fe	Valencia

Sponsors (1)

Lead Sponsor	Collaborator
Fundación IVI

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Study of endometrial regeneration and/or improvement in patients with endometrial pathologies (thin endometrium/Asherman's syndrome/endometrial atrophy) treated with platelet-rich plasma from the umbilical cord by endometrial thickeness.	Improvement will be studied in form of tissue thickening (mm), comparing endometrial thickness before and after PRP injection	An average of 3 months
Secondary	Proof-of-concept in POI patients by improvement endometrial thickeness.	Improvement will be studied in form of tissue thickening (mm), comparing endometrial thickness before and after PRP injection.	An average of 3 months
Secondary	Study of implantation, pregnancy, miscarriage and live newborn rates after injection of the investigational drug (platelet-rich plasma from umbilical cord) by questionnaire at different visits.	If the thickness is good enough, patients will undergo embryo transfer and implantation, pregnancy, miscarriage or live newborn rates will be asked in subsequent visits.	Through study completion, an average of 1 year
Secondary	Gene and protein level evaluation of the endometrial biopsies collected.	Different molecular and histological assays will be performed with the biopsies from all the groups.	An average of 3 years
Secondary	Study of the molecular composition of the different plasma fractions obtained from collected umbilical cord samples.	Different molecular assays will be performed with the blood samples obtained.	An average of 3 years