Clinical trial NCT05095597: Umbilical Cord Plasma for Treating Endometrial Pathologies (Thin Endometrium / Asherman's Syndrome/ Endometria Atrophy)
Official title: Umbilical Cord Plasma for Treating Endometrial Pathologies (Thin Endometrium / Asherman's Syndrome/ Endometria Atrophy).
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Asherman Syndrome
Endometrial Atrophy
Keywords: Endometrial pathology
Platelet-rich plasma
Umbilical cord blood
Regenerative medicine
Lead sponsor: Fundación IVI
Sponsor class: OTHER
First posted: 2021-10-27
Enrollment: 15
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 48
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Recruitment period:

* Umbilical cord donors: throughout the study. Although the aim is to recruit the maximum number of umbilical cord samples during the first 10±3 months of the study. 30±15 donors will be recruited.
* Patients (group A and B): from month 4 of the first year until the end of the study.
* Expected duration of treatment per patient:
* Group A (arms 1 and 2): 22±8 days (visit 2 to visit 3).
* Group B: 22±8 days (visit 2 to visit 3).
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: 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.
timeFrame: An average of 3 months
Secondary outcomes:
measure: Proof-of-concept in POI patients by improvement endometrial thickeness.
timeFrame: An average of 3 months
measure: 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.
timeFrame: Through study completion, an average of 1 year
measure: Gene and protein level evaluation of the endometrial biopsies collected.
timeFrame: An average of 3 years
measure: Study of the molecular composition of the different plasma fractions obtained from collected umbilical cord samples.
timeFrame: An average of 3 years
Other outcomes:
Locations:
city: Valencia
country: Spain
facility: Hospital la Fe
Study officials:
affiliation: Hospital La Fe
name: Mónica Romeu Villaroya, MD., PhD.
role: PRINCIPAL_INVESTIGATOR
affiliation: IVI Foundation/ IIS La Fe
name: Irene Cervelló Alcaráz, PhD.
role: STUDY_DIRECTOR
References: