Asherman SyndromePreENTIRENCT03665649
Pre-clinical Endometrial Tissular Renovation Study
A study testing CD133+ cells isolation in people with Asherman Syndrome, run by Igenomix at 1 site in Spain.
Trial summary
The endometrium is a tissue with high capacity of renewal ("self-renewal"). This process is regulated by stem cells. Recent studies have shown that bone marrow-derived stem cells (BMDSCs) contribute to tissues and organs regeneration, including the murine and human endometrium. Read more about this study
- Who is it for?
- Ages 30 to 45 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Asherman Syndrome
- What is being tested?
- CD133+ cells isolation
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteSpain
- Study dates
- 27 Jul 2018to Oct 2019
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 30 to 45 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Donors of of hematopoietic stem cells whose written informed consent approved by the Ethics Committee (EC) has been obtained, after having been duly informed of the nature of the study and voluntarily accepted to participate after being fully aware of the potential risks, benefits and any discomfort involved.
- Women of reproductive age between 18-44 years old (both inclusive).
- BMI: 18-30 Kg/m2 (both inclusive)
- Adequate hepatic and renal function defined as:
- Total bilirubin <1.5x Higher Normal Validity (VSN)
- Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) <2.5x VSN and
Show all 15Show fewer
- Serum creatinine <1.0 mg/dl; if the serum creatinine is >1.0 mg/dl, the estimated glomerular filtration rate (EGF) should be >60 ml/min/1.73 m2.
- Absence of severe cardiac pathology.
- Negative blood pregnancy test.
- Eastern Cooperative Oncology Group (ECOG) = 0-1.
- Negative serology for HIV, HCV, HBSAg, HBcAg and Syphilis (recent <30 days).
- Normal coagulation study.
- Adequate peripheral venous access.
- Absence of serious psychiatric illness.
- Ability of the donor to understand and comply with the study procedures.
Who cannot join
- Absence of peripheral venous access.
- Patients who have participated in another clinical trial or have received an investigational treatment during the last 30 days, unless the sponsor approves it.
- Existence of serious or uncontrolled bacterial, fungal or viral infections that, could interfere with the participation of the donor in the study or in the evaluation of the results.
- Any disease or unstable medical condition that may endanger the safety of the donor and their compliance with the study. (i.e., previous or current oncological or hematological diseases).
Trial locations and contacts
1 site in 1 country.
Spain1 site, 1 recruiting
- Recruiting
Hospital Vall D´Hebron
Barcelona
Xavier Santamaria, MD PhD, +34 93 206 30 00, xavier.santamaria@igenomix.com
About this study
Official title: Biomedical Study of Toxicity, Biodistribution, Expression and Cellular Characterization of Autologous CD133+ Stem Cells From Donors of Hematopoietic Progenitors (IGX1) in Murine Model With Asherman-induced Syndrome.
The endometrium is a tissue with high capacity of renewal ("self-renewal"). This process is regulated by stem cells. Recent studies have shown that bone marrow-derived stem cells (BMDSCs) contribute to tissues and organs regeneration, including the murine and human endometrium. Additionally, BMDSCs have the ability to differentiate into functional endometrial and stromal epithelial cells.
Asherman's Syndrome (AS) also referred to as intrauterine adhesions (AIU), is an acquired uterine condition characterized by the formation of adhesions inside the uterus. In many cases the front and back walls of the uterus stick to one another. Most patients with AS have menstrual abnormalities, pelvic pain, recurrent miscarriage, and infertility, and psychological disorders. Currently, hysteroscopy is considered the gold standard of methods for the diagnosis of intrauterine adhesions. However, it has a limited capacity for treatment, especially in moderate or severe cases in which permanent infertility can occur. For the first time, our investigation group demonstrated the possibility of regenerating endometrial tissue through bone marrow-derived stem cells (Santamaria et al., 2016).
Read more
This project aims to determine the safety, tolerability and biodistribution of IGX1 (CD133+ cells selected after mobilization and collection of peripheral blood progenitor cells - CPSP) afte rthe intraarterial injection in rats with induced Asherman's Syndrome.
Therefore, the focus of this project is to satisfy the preclinical requirements set out by the the AEMPS (Agencia Española de Medicamentos y Productos Sanitarios) in relation to the Phase I/II clinical trial "Phase I-II clinical trial of advanced, prospective, open, non-randomized, uncontrolled (before-after study), explanatory, multicentre cell therapy , national, intervention with a single treatment group in patients of reproductive age with gestational desire diagnosed with Asherman's Syndrome grade II, III or IV, treated by autologous non-expanded bone marrow stem/progenitor cells selected (IGX1)" (IGX1-ENT-XS-16-01)
Read the detailed description
The endometrium is the tissue that lines the inside of the uterine cavity and whose function is to enable implantation of the embryo at the right moment. When implantation of the embryo does not occur, the endometrium is partially destroyed and menstruation takes place, producing a new generation of tissue in the next menstrual cycle. It is therefore a high dynamic tissue undergoing changes of growth, differentiation and shedding every 28 days during 400-500 cycles during a woman's reproductive lifetime. This level of tissue regeneration is comparable to other tissues with high cellular turnover, such as epidermis, gut epithelium and bone marrow. This highly regenerative self-renewal capacity of the endometrium seems to be regulated by stem cells. An increased number of studies about endometrium-derived stem cells have been published in the last years. Furthermore, bone marrow-derived stem cells (BMDSCs) have been shown to contribute to the repair and regeneration of tissues and organs, including human and murine endometrium.
Asherman's Syndrome (AS) is characterized by intrauterine adhesions and is associated with infertility due to loss of normal endometrium. Hysteroscopy is the gold standard of methods for diagnosis of these intrauterine adhesions. However, it has certain potential complications such as uterine perforation and the possibility of adhesion recurrence in moderate and severe cases.
Therefore, stem cell therapy targeting the endometrium with the aim of replacing the damaged tissue, offers a promising approach for treating AS and Endometrial atrophy (EA). In a pilot trial, our research group demonstrated, for the first time, that CD133+ BMDSC autologous cell therapy may be useful in treating patients with AS and EA and a wish to conceive. These cells are capable of inducing proliferation of the neighbouring endometrial cells in the damaged endometrium. Given these results, the European Medicines Agency (EMA) approved the designation of orphan drug (ODD) to the investigational product IGX1 (treatment with autologous CD133+ stem cells) for the experimental treatment of Asherman's Syndrome (EMA/OD/313/16).
Based on these previous facts, a phase I/II clinical trial "ENTIRE" (code IGX1-ENT-XS-16-01 and European Union Drug Regulating Authorities Clinical Trials -EudraCT- number 2016-003975-23) was designed.
In order to study relevant effects of stem cell therapy in AS and respond to the clarifications requested by the AEMPs (Agencia Española de Medicamentos y Productos Sanitarios), the main objective of the present study is to evaluate the safety, tolerability, as well as the biodistribution, expression and cellular characterization of IGX1 (CD133+ cells selected after mobilization and collection of peripheral blood progenitor cells - CPSP) in a murine model with Asherman-induced Syndrome (preclinical study). In addition, other possible endothelial and blood markers of this cellular subpopulation will be characterized by flow cytometry, as well as the viability and potency of these cells.
- Conditions
- Asherman Syndrome
- Being tested
- CD133+ cells isolation
- Keywords
- Asherman Syndrome, Bone marrow-derived stem cells, Endometrial regeneration, Assisted reproduction techniques, Endometrial physiopathology, CD133+, Endometrial atrophy, Endometrial thickness
- Medical subject headings
- Gynatresia, Macular Dystrophy, Retinal, 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CD133+ cells isolationProcedure or surgery
Hematopoietic precursors from human donors will be mobilized by administering Colony Stimulating Factors (G-CSF) for 5 days (according to the clinical standard administration) and subsequently CD133+ cells will be isolated and transferred in a murine model.
| Study group | Role | What they receive |
|---|---|---|
| CD133+ human donors | Other | CD133+ cells isolation Receives: Procedure: CD133+ cells isolation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of CD133+
Total number of CD133+ obtained after the apheresis
Measured: 0 hours
Polymorphonuclear cells
Total number of polymorphonuclear cells obtained
Measured: 0 hours
Secondary outcomes (4)
Percentage of viable cells
Evaluation of cell viability
Measured: 0 hours, 3 hours and 18 hours
Number of Colony-forming unit (CFU)
The number of viable bacteria or fungal cells in the sample
Measured: 0 hours, 3 hours and 18 hours
Concentration of Pathogens
Cells culture and gram stain
Measured: 0 hours
Expression of hematopoietic stem cells (subtypes: CD133+, CD56+, CD66+, CD14+, CD19+, CD3+, CD45+, CD34+)
Isolation stem cells by Fluorescence Activated Cell Sorting Cytometry (FACS)
Measured: 18 hours from extraction
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Sep 2018
- Study start27 Jul 2018
- Primary completionOct 2019 (estimated)
- Study completionOct 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Asherman SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 5 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Igenomix
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Xavier Santamaria, MD PhD, Principal investigator, Hospital Vall d'Hebron
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03665649
- Sponsor's protocol ID
- IGX1-ASM-XS-18-06
- Acronym
- PreENTIRE
- Status last verified
- Jul 2019
- First submitted
- 7 Sep 2018
- Last updated
- 17 Jul 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Biomedical Study of Toxicity, Biodistribution, Expression and Cellular Characterization of Autologous CD133+ Stem Cells From Donors of Hematopoietic Progenitors (IGX1) in Murine Model With Asherman-induced Syndrome.
- ClinicalTrials.gov ID
- NCT03665649
- Acronym / sponsor ID
- PreENTIRE / IGX1-ASM-XS-18-06
- Conditions
- Asherman Syndrome
- Keywords
- Asherman Syndrome, Bone marrow-derived stem cells, Endometrial regeneration, Assisted reproduction techniques, Endometrial physiopathology, CD133+, Endometrial atrophy, Endometrial thickness
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 5 participants (estimated)
- Lead sponsor
- IgenomixIndustry (pharma, biotech, devices)
- Study start
- 27 Jul 2018 (actual)
- Primary completion
- Oct 2019 (estimated)
- Study completion
- Oct 2019 (estimated)
- First posted
- 11 Sep 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The endometrium is a tissue with high capacity of renewal ("self-renewal"). This process is regulated by stem cells. Recent studies have shown that bone marrow-derived stem cells (BMDSCs) contribute to tissues and organs regeneration, including the murine and human endometrium. Additionally, BMDSCs have the ability to differentiate into functional endometrial and stromal epithelial cells.
Asherman's Syndrome (AS) also referred to as intrauterine adhesions (AIU), is an acquired uterine condition characterized by the formation of adhesions inside the uterus. In many cases the front and back walls of the uterus stick to one another. Most patients with AS have menstrual abnormalities, pelvic pain, recurrent miscarriage, and infertility, and psychological disorders. Currently, hysteroscopy is considered the gold standard of methods for the diagnosis of intrauterine adhesions. However, it has a limited capacity for treatment, especially in moderate or severe cases in which permanent infertility can occur. For the first time, our investigation group demonstrated the possibility of regenerating endometrial tissue through bone marrow-derived stem cells (Santamaria et al., 2016).
This project aims to determine the safety, tolerability and biodistribution of IGX1 (CD133+ cells selected after mobilization and collection of peripheral blood progenitor cells - CPSP) afte rthe intraarterial injection in rats with induced Asherman's Syndrome.
Therefore, the focus of this project is to satisfy the preclinical requirements set out by the the AEMPS (Agencia Española de Medicamentos y Productos Sanitarios) in relation to the Phase I/II clinical trial "Phase I-II clinical trial of advanced, prospective, open, non-randomized, uncontrolled (before-after study), explanatory, multicentre cell therapy , national, intervention with a single treatment group in patients of reproductive age with gestational desire diagnosed with Asherman's Syndrome grade II, III or IV, treated by autologous non-expanded bone marrow stem/progenitor cells selected (IGX1)" (IGX1-ENT-XS-16-01)
Detailed description
The endometrium is the tissue that lines the inside of the uterine cavity and whose function is to enable implantation of the embryo at the right moment. When implantation of the embryo does not occur, the endometrium is partially destroyed and menstruation takes place, producing a new generation of tissue in the next menstrual cycle. It is therefore a high dynamic tissue undergoing changes of growth, differentiation and shedding every 28 days during 400-500 cycles during a woman's reproductive lifetime. This level of tissue regeneration is comparable to other tissues with high cellular turnover, such as epidermis, gut epithelium and bone marrow. This highly regenerative self-renewal capacity of the endometrium seems to be regulated by stem cells. An increased number of studies about endometrium-derived stem cells have been published in the last years. Furthermore, bone marrow-derived stem cells (BMDSCs) have been shown to contribute to the repair and regeneration of tissues and organs, including human and murine endometrium.
Asherman's Syndrome (AS) is characterized by intrauterine adhesions and is associated with infertility due to loss of normal endometrium. Hysteroscopy is the gold standard of methods for diagnosis of these intrauterine adhesions. However, it has certain potential complications such as uterine perforation and the possibility of adhesion recurrence in moderate and severe cases.
Therefore, stem cell therapy targeting the endometrium with the aim of replacing the damaged tissue, offers a promising approach for treating AS and Endometrial atrophy (EA). In a pilot trial, our research group demonstrated, for the first time, that CD133+ BMDSC autologous cell therapy may be useful in treating patients with AS and EA and a wish to conceive. These cells are capable of inducing proliferation of the neighbouring endometrial cells in the damaged endometrium. Given these results, the European Medicines Agency (EMA) approved the designation of orphan drug (ODD) to the investigational product IGX1 (treatment with autologous CD133+ stem cells) for the experimental treatment of Asherman's Syndrome (EMA/OD/313/16).
Based on these previous facts, a phase I/II clinical trial "ENTIRE" (code IGX1-ENT-XS-16-01 and European Union Drug Regulating Authorities Clinical Trials -EudraCT- number 2016-003975-23) was designed.
In order to study relevant effects of stem cell therapy in AS and respond to the clarifications requested by the AEMPs (Agencia Española de Medicamentos y Productos Sanitarios), the main objective of the present study is to evaluate the safety, tolerability, as well as the biodistribution, expression and cellular characterization of IGX1 (CD133+ cells selected after mobilization and collection of peripheral blood progenitor cells - CPSP) in a murine model with Asherman-induced Syndrome (preclinical study). In addition, other possible endothelial and blood markers of this cellular subpopulation will be characterized by flow cytometry, as well as the viability and potency of these cells.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CD133+ human donors | Other | Procedure: CD133+ cells isolationCD133+ cells isolation |
Who may qualify
- Ages
- 30 to 45 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (15 listed)
- Donors of of hematopoietic stem cells whose written informed consent approved by the Ethics Committee (EC) has been obtained, after having been duly informed of the nature of the study and voluntarily accepted to participate after being fully aware of the potential risks, benefits and any discomfort involved.
- Women of reproductive age between 18-44 years old (both inclusive).
- BMI: 18-30 Kg/m2 (both inclusive)
- Adequate hepatic and renal function defined as:
- Absence of severe cardiac pathology.
Key exclusion criteria (4 listed)
- Absence of peripheral venous access.
- Patients who have participated in another clinical trial or have received an investigational treatment during the last 30 days, unless the sponsor approves it.
- Existence of serious or uncontrolled bacterial, fungal or viral infections that, could interfere with the participation of the donor in the study or in the evaluation of the results.
- Any disease or unstable medical condition that may endanger the safety of the donor and their compliance with the study. (i.e., previous or current oncological or hematological diseases).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CD133+ cells isolationHematopoietic precursors from human donors will be mobilized by administering Colony Stimulating Factors (G-CSF) for 5 days (according to the clinical standard administration) and subsequently CD133+ cells will be isolated and transferred in a murine model. | Procedure or surgery | CD133+ human donors |
Primary outcome
Number of CD133+
Time frame: 0 hours
Total number of CD133+ obtained after the apheresis
Polymorphonuclear cells
Time frame: 0 hours
Total number of polymorphonuclear cells obtained
4 secondary outcomes
Percentage of viable cells
Time frame: 0 hours, 3 hours and 18 hours
Number of Colony-forming unit (CFU)
Time frame: 0 hours, 3 hours and 18 hours
Concentration of Pathogens
Time frame: 0 hours
Expression of hematopoietic stem cells (subtypes: CD133+, CD56+, CD66+, CD14+, CD19+, CD3+, CD45+, CD34+)
Time frame: 18 hours from extraction
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jul 2019.
- Individual participant dataSharing planned: No
Related trials for Asherman Syndrome
Recruiting
CURENDO (Cord-blood Uterine Regeneration Endometrium): Platelet-rich Plasma Therapy Derived From Umbilical Cord Blood for the Treatment of Endometrial Pathologies (Asherman Syndrome / Endometrial Atrophy / Thin Endometrium)
Asherman Syndrome
RecruitingPhase 1
AD-SVF Therapy for Refractory Endometrial Infertility
Endometrium; Atrophy, Intrauterine Synechiae
RecruitingEarly Phase 1
Bone Marrow Derived Stem Cells Mobilization for Treatment of Abnormal Endometrium
Asherman Syndrome, Atrophic Endometrium
Not yet recruitingObservational study
Safety and Performance of the Semical Adhesion Barrier Gel for Prevention of Intra-uterine Adhesion
Intrauterine Abnormalities in Infertility, Asherman Syndrome
Active, not recruitingPhase 1/2
Study on the Effective Dose and Safety of Esketamine in Hysteroscopic Surgery Under Monitored Anesthesia Care
Intrauterine Polyp, Intrauterine Synechiae
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Xavier Santamaria, MD PhD principal investigator
Hospital Vall d'Hebron
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing CD133+ cells isolation in people with Asherman Syndrome, run by Igenomix at 1 site in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 17 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Carlos Gomez, BSc MSc (+34 96 390 53 10 ext. 18543, carlos.gomez@igenomix.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of CD133+ (time frame: 0 hours). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Jul 2019.