Thin EndometriumPhase 2NCT03067623
Autologous Platelet-Rich Plasma (PRP) and Endometrial Thickness
A Phase 2 study testing PRP and Tomcat catheter in people with Thin Endometrium and Endometrial Disorder, run by University Magna Graecia at 1 site in Italy.
Trial summary
The goal of this interventional study is to evaluate the increasing in endometrial thickening after the intrauterine infusion of 0,5-1 ml of autologous Platelet-Rich Plasma (PRP) and the implantation rate in women with thin endometrium undergoing Embryo-transfer, in order to propose a novel therapeutic approach for… Read more about this study
- Who is it for?
- Ages 18 to 46 years, women only
- Conditions the study is for
- Thin Endometrium, Endometrial Disorder, Endometrial Thickness Not Growing Under Estrogen Stimulation
- What is being tested?
- PRP and Tomcat catheter
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 200 participants
- Where
- 1 siteItaly
- Study dates
- 27 Feb 2017to 27 Feb 2020
- Phase
- Phase 2
- 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 18 to 46 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- Endometrial thickness < 7 mm under estrogen replacement therapy or repeated implantation failure
- Age between 18 and 46 years
Who cannot join
- Age < 18 and > 46 years
- Pregnancy
- Bleeding diathesis
- Previous uterine surgery (miomectomy, cesarean section, etc...)
- Platelet count < 105/μL
- Hemoglobin < 10 g/dL
Show all 9Show fewer
- Presence of a tumor in the wound bed or metastatic disease
- Current diagnosis of cancer
- Other concomitant active infections
Trial locations and contacts
1 site in 1 country.
Italy1 site, 1 recruiting
- Recruiting
Pugliese Ciaccio Hospital
Catanzaro, 88100
Roberta Venturella, MD, +390961883234, venturella@unicz.it
Adalgisa Brescia, MD
About this study
Official title: Intrauterine Infusion of Autologous Platelet-Rich Plasma (PRP) in Women With Thin Endometrium Undergoing Embryo-transfer.
The goal of this interventional study is to evaluate the increasing in endometrial thickening after the intrauterine infusion of 0,5-1 ml of autologous Platelet-Rich Plasma (PRP) and the implantation rate in women with thin endometrium undergoing Embryo-transfer, in order to propose a novel therapeutic approach for women with an endometrium < 7 mm unresponsive to standard treatments.
Read the detailed description
In clinical practice, a thin endometrium, unresponsive to conventional therapies, usually results in cycle cancellation and embryo cryopreservation. The evaluation of an adequate endometrial growth is performed using grey-scale ultrasound. The minimal endometrial thickness required for embryo transfer is now considered about 7 mm at the end of natural or medically induced follicular phase, despite some investigators reported different cutoff values, ranging between 7 and 10 mm. Currently, no evidence-based data show the predictive positive value of endometrial thickness on pregnancy rate after Embryo-transfer, but if the endometrial lining is below 7mm the chance of pregnancy is statistically significant reduced.
Thin endometrium is relatively frequent in women with previous trauma of the uterus (cesarean sections, repetitive curettage), patients subjected to antitumoral treatments in childhood (Radiotherapy, Chemotherapy, Surgery), women affected by Asherman's syndrome, chronic infections (endometritis, Pelvic Inflammatory Disease) and inadequate blood flow (stress, malposition of uterus, fibrosis), patients with low estradiol values or excessive use of Clomiphene Citrate.
Several alternative treatments have been proposed over the years to improve the endometrial thickening, then showed themselves to be not considered the answer in many cases: some of them, indeed, require a not damaged endometrium, other act on endometrial blood flow and have no direct proliferative effect on the endometrium. The only factor presumed to have a proliferative effect on endometrium is the Granulocyte-Colony Stimulating Factor (G-CSF) but this hypothesis is not supported by in vitro studies.
Recently, first results from an in vitro study ongoing on the evaluation of Platelet-Rich Plasma (PRP) effect on endometrial cell proliferation have been presented (Aghayanova et al., 2016). The authors demonstrated that PRP increased proliferation not only on cultured fibroblasts, as currently known but also on mesenchymal cells, which are progenitors of different types of cells, including endometrial cells. This evidence supports the hypothesis that PRP stimulates some of the cellular processes involved in endometrial regeneration, that can be relevant to the management of a thin lining.
Autologous Platelet-Rich Plasma is prepared from fresh whole blood which is collected from a peripheral vein and processed to separate platelets from the other blood components. PRP contains activating platelets that stimulate the action of cytokines and growth factors. On the basis of this evidence, local intrauterine infusion of PRP may improve endometrial growth and implantation.
Patients considered to be candidates for a PRP application must undergo a minor hematological evaluation to exclude blood disorders or platelet dysfunction. The study, since it involves the use of a blood component, was approved by Ethical Committee and all participant have to sign an informed written consent before undergoing the procedure.
Any concerns of immunogenic reactions or disease transmission, that exist with homologous blood products, are eliminated because PRP is produced from autologous blood. Preparation of PRP, however, demands many processing steps, thus there is the theoretic possibility of contamination. For these reasons, all samples are subjected to quality and sterility controls within a closed mechanism. No wound infections after PRP applications have been reported. Despite PGF has mitogenic properties, there is no evidence that the growth factors included in PRP promote tumor growth or that they are involved in carcinogenesis.
- Conditions
- Thin Endometrium, Endometrial Disorder, Endometrial Thickness Not Growing Under Estrogen Stimulation
- Being tested
- PRP, Tomcat catheter
- Keywords
- Thin endometrium, Endometrial thickness
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PRPDrug
PRP intrauterine infusion
Tomcat catheterDevice
PRP intrauterine infusion by means Tomcat catheter
| Study group | Role | What they receive |
|---|---|---|
| PRP-infusion | Experimental | PRP will be obtained from a fresh whole blood collected from a peripheral vein; the blood sample will be centrifuged at 1500g (RCF) for 10 minutes and the repeated reversal of the tube will allow obtaining the PRP at the concentration required. Then 0,5-1ml of PRP will be infused into the uterine cavity through a Tomcat catheter. The endometrial thickening will be evaluated by ultrasonography 24-48h after the instillation and, if the endometrial lining reaches 7mm the Embryo-transfer will be arranged. Receives: Drug: PRP; Device: Tomcat catheter |
What is being measured
The primary outcome is the main question the study is designed to answer.
Endometrial thickness
Endometrial thickness > 7 mm measured by means of transvaginal ultrasound
Measured: 24-48h after the intrauterine PRP infusion
Secondary outcomes (2)
Positive pregnancy test rate
Positive pregnancy test rate after Embryo-transfer
Measured: Approximately 3 weeks after treatment
Implantation rate
defined by number of gestational sacs seen on early pregnancy 6-week ultrasound divided by number of embryos transferred
Measured: Approximately 6 weeks after treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Mar 2017
- Study start27 Feb 2017
- Primary completion31 Dec 2019 (estimated)
- Study completion27 Feb 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Thin EndometriumStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Magna Graecia
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Roberta Venturella, University Magna Graecia
- Investigators
- Roberta Venturella, MD, Principal investigator, Magna Graecia University of Catanzaro
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03067623
- Sponsor's protocol ID
- PRP-Et
- Status last verified
- May 2019
- First submitted
- 26 Feb 2017
- Last updated
- 23 May 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Chang Y, Li J, Chen Y, Wei L, Yang X, Shi Y, Liang X. Autologous platelet-rich plasma promotes endometrial growth and improves pregnancy outcome during in vitro fertilization. Int J Clin Exp Med. 2015 Jan 15;8(1):1286-90. eCollection 2015.
PubMed 25785127Nazari L, Salehpour S, Hoseini S, Zadehmodarres S, Ajori L. Effects of autologous platelet-rich plasma on implantation and pregnancy in repeated implantation failure: A pilot study. Int J Reprod Biomed. 2016 Oct;14(10):625-628.
PubMed 27921085L. Aghajanova, S. Houshdaran, S. Balayan, J. Irwin, H. Huddleston, L. Giudice. Platelets for endometrial regeneration: a novel approach. Fertil Steril. Volume 106, Issue 3, Supplement, Page e82
Study at a glance
From the registry record, last updated by the sponsor on 23 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Intrauterine Infusion of Autologous Platelet-Rich Plasma (PRP) in Women With Thin Endometrium Undergoing Embryo-transfer.
- ClinicalTrials.gov ID
- NCT03067623
- Acronym / sponsor ID
- PRP-Et
- Conditions
- Thin Endometrium, Endometrial Disorder, Endometrial Thickness Not Growing Under Estrogen Stimulation
- Keywords
- Thin endometrium, Endometrial thickness
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- University Magna GraeciaUniversity, hospital or other
- Study start
- 27 Feb 2017 (actual)
- Primary completion
- 31 Dec 2019 (estimated)
- Study completion
- 27 Feb 2020 (estimated)
- First posted
- 1 Mar 2017 (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 goal of this interventional study is to evaluate the increasing in endometrial thickening after the intrauterine infusion of 0,5-1 ml of autologous Platelet-Rich Plasma (PRP) and the implantation rate in women with thin endometrium undergoing Embryo-transfer, in order to propose a novel therapeutic approach for women with an endometrium < 7 mm unresponsive to standard treatments.
Detailed description
In clinical practice, a thin endometrium, unresponsive to conventional therapies, usually results in cycle cancellation and embryo cryopreservation. The evaluation of an adequate endometrial growth is performed using grey-scale ultrasound. The minimal endometrial thickness required for embryo transfer is now considered about 7 mm at the end of natural or medically induced follicular phase, despite some investigators reported different cutoff values, ranging between 7 and 10 mm. Currently, no evidence-based data show the predictive positive value of endometrial thickness on pregnancy rate after Embryo-transfer, but if the endometrial lining is below 7mm the chance of pregnancy is statistically significant reduced.
Thin endometrium is relatively frequent in women with previous trauma of the uterus (cesarean sections, repetitive curettage), patients subjected to antitumoral treatments in childhood (Radiotherapy, Chemotherapy, Surgery), women affected by Asherman's syndrome, chronic infections (endometritis, Pelvic Inflammatory Disease) and inadequate blood flow (stress, malposition of uterus, fibrosis), patients with low estradiol values or excessive use of Clomiphene Citrate.
Several alternative treatments have been proposed over the years to improve the endometrial thickening, then showed themselves to be not considered the answer in many cases: some of them, indeed, require a not damaged endometrium, other act on endometrial blood flow and have no direct proliferative effect on the endometrium. The only factor presumed to have a proliferative effect on endometrium is the Granulocyte-Colony Stimulating Factor (G-CSF) but this hypothesis is not supported by in vitro studies.
Recently, first results from an in vitro study ongoing on the evaluation of Platelet-Rich Plasma (PRP) effect on endometrial cell proliferation have been presented (Aghayanova et al., 2016). The authors demonstrated that PRP increased proliferation not only on cultured fibroblasts, as currently known but also on mesenchymal cells, which are progenitors of different types of cells, including endometrial cells. This evidence supports the hypothesis that PRP stimulates some of the cellular processes involved in endometrial regeneration, that can be relevant to the management of a thin lining.
Autologous Platelet-Rich Plasma is prepared from fresh whole blood which is collected from a peripheral vein and processed to separate platelets from the other blood components. PRP contains activating platelets that stimulate the action of cytokines and growth factors. On the basis of this evidence, local intrauterine infusion of PRP may improve endometrial growth and implantation.
Patients considered to be candidates for a PRP application must undergo a minor hematological evaluation to exclude blood disorders or platelet dysfunction. The study, since it involves the use of a blood component, was approved by Ethical Committee and all participant have to sign an informed written consent before undergoing the procedure.
Any concerns of immunogenic reactions or disease transmission, that exist with homologous blood products, are eliminated because PRP is produced from autologous blood. Preparation of PRP, however, demands many processing steps, thus there is the theoretic possibility of contamination. For these reasons, all samples are subjected to quality and sterility controls within a closed mechanism. No wound infections after PRP applications have been reported. Despite PGF has mitogenic properties, there is no evidence that the growth factors included in PRP promote tumor growth or that they are involved in carcinogenesis.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| PRP-infusion | Experimental | Drug: PRP, Device: Tomcat catheterPRP will be obtained from a fresh whole blood collected from a peripheral vein; the blood sample will be centrifuged at 1500g (RCF) for 10 minutes and the repeated reversal of the tube will allow obtaining the PRP at the concentration required. Then 0,5-1ml of PRP will be infused into the uterine cavity through a Tomcat catheter. The endometrial thickening will be evaluated by ultrasonography 24-48h after the instillation and, if the endometrial lining reaches 7mm the Embryo-transfer will be arranged. |
Who may qualify
- Ages
- 18 to 46 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- Endometrial thickness < 7 mm under estrogen replacement therapy or repeated implantation failure
- Age between 18 and 46 years
Key exclusion criteria (9 listed)
- Age < 18 and > 46 years
- Pregnancy
- Bleeding diathesis
- Previous uterine surgery (miomectomy, cesarean section, etc...)
- Platelet count < 105/μL
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 |
|---|---|---|
| PRPPRP intrauterine infusion | Drug | PRP-infusion |
| Tomcat catheterPRP intrauterine infusion by means Tomcat catheter | Device | PRP-infusion |
Primary outcome
Endometrial thickness
Time frame: 24-48h after the intrauterine PRP infusion
Endometrial thickness > 7 mm measured by means of transvaginal ultrasound
2 secondary outcomes
Positive pregnancy test rate
Time frame: Approximately 3 weeks after treatment
Implantation rate
Time frame: Approximately 6 weeks after treatment
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 May 2019.
- Background: PubMed 25785127Chang Y, Li J, Chen Y, Wei L, Yang X, Shi Y, Liang X. Autologous platelet-rich plasma promotes endometrial growth and improves pregnancy outcome during in vitro fertilization. Int J Clin Exp Med. 2015 Jan 15;8(1):1286-90. eCollection 2015.
- Background: PubMed 27921085Nazari L, Salehpour S, Hoseini S, Zadehmodarres S, Ajori L. Effects of autologous platelet-rich plasma on implantation and pregnancy in repeated implantation failure: A pilot study. Int J Reprod Biomed. 2016 Oct;14(10):625-628.
- BackgroundL. Aghajanova, S. Houshdaran, S. Balayan, J. Irwin, H. Huddleston, L. Giudice. Platelets for endometrial regeneration: a novel approach. Fertil Steril. Volume 106, Issue 3, Supplement, Page e82
- Ongoing TrialLink provided by the sponsor.
- Individual participant dataSharing planned: No
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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.
Roberta Venturella, MD principal investigator
Magna Graecia University of Catanzaro
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing PRP and Tomcat catheter in people with Thin Endometrium and Endometrial Disorder, run by University Magna Graecia at 1 site in Italy.
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 2 inclusion and 9 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 23 May 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 Italy. 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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 Roberta Venturella, MD (+390961883234, venturella@unicz.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Endometrial thickness (time frame: 24-48h after the intrauterine PRP infusion). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03067623, which also lists 3 linked publications.
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 23 May 2019.