Back to resultsUmbilical Cord Plasma for Treating Endometrial Pathologies (Thin Endometrium / Asherman's Syndrome/ Endometria Atrophy) (hSCU-PRP)
Primary Purpose
Asherman Syndrome, Endometrial Atrophy
Status
Recruiting
Phase
Phase 2
Locations
Spain
Study Type
Interventional
Intervention
Injection of hUC-PRP by hysteroscopy
Oestraclin
Umbilical cord blood collection
Endometrial biopsy
Sponsored by
About this trial
This is an interventional treatment trial for Asherman Syndrome focused on measuring Endometrial pathology, Platelet-rich plasma, Umbilical cord blood, Regenerative medicine
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.
Sites / Locations
- Hospital la FeRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm Type
Other
Experimental
Other
Other
Other
Arm Label
Umbilical cord PRP donors
Group B- Asherman with PRP treatment and estrogen therapy
Group A1- POI with PRP treatment and estrogen therapy
Group A2- POI with estrogen therapy
Group A3- POI without PRP treatment nor estrogen therapy
Arm Description
Women who are going to give birth to a healthy live newborn at the Hospital Universitario y Politécnico La Fe. Donors will donate their umbilical cord blood to obtain the hUC-PRP. A total of 30±15 donors will be recruited.
Women with thin endometrium/endometrial atrophy and/or Asherman's syndrome with fertility problems and reproductive desires, desires that could be achieved by their participation in the present study. A total of 15 patients will be included; all of them will receive the investigational treatment as well as estrogen therapy.
Women with premature ovarian failure (POI). A total of 10 patients will be included. All of them will receive the investigational treatment as well as estrogen therapy.
Women with premature ovarian failure (POI). A total of 10 patients will be included. All of them will receive the estrogen therapy.
Women with premature ovarian failure (POI). A total of 10 patients will be included. None of them will receive either the investigational treatment nor estrogen therapy.
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
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.
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.
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05095597
Brief Title
Umbilical Cord Plasma for Treating Endometrial Pathologies (Thin Endometrium / Asherman's Syndrome/ Endometria Atrophy)
Acronym
hSCU-PRP
Official Title
Umbilical Cord Plasma for Treating Endometrial Pathologies (Thin Endometrium / Asherman's Syndrome/ Endometria Atrophy).
Study Type
Interventional
2. Study Status
Record Verification Date
January 2023
Overall Recruitment Status
Recruiting
Study Start Date
April 22, 2022 (Actual)
Primary Completion Date
October 2023 (Anticipated)
Study Completion Date
November 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Fundación IVI
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Asherman Syndrome, Endometrial Atrophy
Keywords
Endometrial pathology, Platelet-rich plasma, Umbilical cord blood, Regenerative medicine
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
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).
Masking
None (Open Label)
Allocation
Randomized
Enrollment
45 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Umbilical cord PRP donors
Arm Type
Other
Arm Description
Women who are going to give birth to a healthy live newborn at the Hospital Universitario y Politécnico La Fe.
Donors will donate their umbilical cord blood to obtain the hUC-PRP. A total of 30±15 donors will be recruited.
Arm Title
Group B- Asherman with PRP treatment and estrogen therapy
Arm Type
Experimental
Arm Description
Women with thin endometrium/endometrial atrophy and/or Asherman's syndrome with fertility problems and reproductive desires, desires that could be achieved by their participation in the present study. A total of 15 patients will be included; all of them will receive the investigational treatment as well as estrogen therapy.
Arm Title
Group A1- POI with PRP treatment and estrogen therapy
Arm Type
Other
Arm Description
Women with premature ovarian failure (POI). A total of 10 patients will be included. All of them will receive the investigational treatment as well as estrogen therapy.
Arm Title
Group A2- POI with estrogen therapy
Arm Type
Other
Arm Description
Women with premature ovarian failure (POI). A total of 10 patients will be included. All of them will receive the estrogen therapy.
Arm Title
Group A3- POI without PRP treatment nor estrogen therapy
Arm Type
Other
Arm Description
Women with premature ovarian failure (POI). A total of 10 patients will be included. None of them will receive either the investigational treatment nor estrogen therapy.
Intervention Type
Procedure
Intervention Name(s)
Injection of hUC-PRP by hysteroscopy
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Oestraclin
Intervention Description
Patients will receive estrogenic therapy, based on estradiol, for 10±2 days (oestraclin, topical cream, 5µg daily for 10±2 days).
Intervention Type
Procedure
Intervention Name(s)
Umbilical cord blood collection
Intervention Description
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.
Intervention Type
Procedure
Intervention Name(s)
Endometrial biopsy
Intervention Description
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.
Primary Outcome Measure Information:
Title
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.
Description
Improvement will be studied in form of tissue thickening (mm), comparing endometrial thickness before and after PRP injection
Time Frame
An average of 3 months
Secondary Outcome Measure Information:
Title
Proof-of-concept in POI patients by improvement endometrial thickeness.
Description
Improvement will be studied in form of tissue thickening (mm), comparing endometrial thickness before and after PRP injection.
Time Frame
An average of 3 months
Title
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.
Description
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.
Time Frame
Through study completion, an average of 1 year
Title
Gene and protein level evaluation of the endometrial biopsies collected.
Description
Different molecular and histological assays will be performed with the biopsies from all the groups.
Time Frame
An average of 3 years
Title
Study of the molecular composition of the different plasma fractions obtained from collected umbilical cord samples.
Description
Different molecular assays will be performed with the blood samples obtained.
Time Frame
An average of 3 years
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
48 Years
Accepts Healthy Volunteers
No
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Irene Cervelló Alcaráz, PhD.
Phone
+34963903305
Email
irene.cervello@ivirma.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mónica Romeu Villaroya, MD., PhD.
Organizational Affiliation
Hospital La Fe
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Irene Cervelló Alcaráz, PhD.
Organizational Affiliation
IVI Foundation/ IIS La Fe
Official's Role
Study Director
Facility Information:
Facility Name
Hospital la Fe
City
Valencia
ZIP/Postal Code
46026
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Adolfo Rodriguez
12. IPD Sharing Statement
Learn more about this trial
Umbilical Cord Plasma for Treating Endometrial Pathologies (Thin Endometrium / Asherman's Syndrome/ Endometria Atrophy)
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