Bone Marrow Stem Cell Treatment for Asherman's Syndrome and Endometrial Atrophy

NCT ID: NCT02144987

Last Updated: 2015-04-22

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

16 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-04-30

Study Completion Date

2014-09-30

Brief Summary

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The purpose of this study is to determine whether Bone Marrow Stem Cell transplantation may improve Assisted Reproduction Techniques (ART) outcomes in refractive Asherman's Syndrome or Atrophic Endometrium.

Detailed Description

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This novel technique refers to the use of CD133+ autologous bone marrow stem-cells to regenerate the endometrium in patients with Asherman's Syndrome, Endometrial Atrophy or any condition that produce a destruction of the endometrium or its de novo creation in a bioengineered uterus.

It requires a previous mobilization in the peripheral blood of CD133+ autologous bone marrow stem cells, subsequent apheresis and transplant of the same cells in the spiral arterioles of the uterus with the aim to regenerate de novo the endometrium. This technique represents a new therapeutical approach for the treatment of endometrial regeneration problems such Asherman Syndrome and the endometrial atrophy since currently no specific treatment for these endometrial pathologies exist.

A prospective experimental non controlled study has been designed in order to assess the effectiveness of these technique as a new tool for treat Asherman's Syndrome and Endometrial Atrophy.

Conditions

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Asherman's Syndrome Endometrium; Atrophy, Cervix

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Interventions

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Bone Marrow CD133+ Stem Cell Transplantation

1. Bone Marrow Stem Cell (BMSC) mobilization peripheral blood induced by granulocyte-CSF (G-CSF) 5 mcg/kg sc every 12 hours for 4 days.
2. BMSC recollection with apheresis procedure and positive selection of the CD133+ cells.

The selection procedure will be performed for a maximum of 3 hours or until at least 50 million cells are collected.
3. CD133+ cells transplantation into the uterine spiral arterioles by intra-arterial catheterization
4. Subsequently Hormonal Replacement Therapy (HRT) will be given to the patients
5. Hysteroscopy will be performed 2-3 months after stem cell transplantation
6. Embryo transfer will be performed 3-6 months after stem cell transplantation with HRT endometrial preparation

Intervention Type BIOLOGICAL

Other Intervention Names

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Neupogen

Eligibility Criteria

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Inclusion Criteria

* Patients diagnosed of Asherman Syndrome and absence of pregnancy after treatment
* Endometrial atrophy (\<6mm) with Implantation Failure
* Age 20-45 years-old
* Normal liver, heart and kidney function
* Presence of menstrual bleeding with Natural Cycle or HRT
* Absence of psychiatric pathology and ability to accomplish the treatment
* β-hCG negative
* Absence of SDT

Exclusion Criteria

* Absence of peripheral vein access
Minimum Eligible Age

18 Years

Maximum Eligible Age

45 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Fundación para la Investigación del Hospital Clínico de Valencia

OTHER

Sponsor Role collaborator

Instituto Valenciano de Infertilidad, IVI VALENCIA

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Xavier Santamaria, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Instituto Valenciano Infertilidad

Carlos Simon, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Instituto Valenciano Infertilidad

Locations

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Hospital Clinico y Universitario de Valencia

Valencia, Valencia, Spain

Site Status

Instituto Valenciano Infertilidad

Valencia, Valencia, Spain

Site Status

Countries

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Spain

References

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Chan RW, Schwab KE, Gargett CE. Clonogenicity of human endometrial epithelial and stromal cells. Biol Reprod. 2004 Jun;70(6):1738-50. doi: 10.1095/biolreprod.103.024109. Epub 2004 Feb 6.

Reference Type BACKGROUND
PMID: 14766732 (View on PubMed)

Cervello I, Gil-Sanchis C, Mas A, Faus A, Sanz J, Moscardo F, Higueras G, Sanz MA, Pellicer A, Simon C. Bone marrow-derived cells from male donors do not contribute to the endometrial side population of the recipient. PLoS One. 2012;7(1):e30260. doi: 10.1371/journal.pone.0030260. Epub 2012 Jan 19.

Reference Type BACKGROUND
PMID: 22276168 (View on PubMed)

Ikoma T, Kyo S, Maida Y, Ozaki S, Takakura M, Nakao S, Inoue M. Bone marrow-derived cells from male donors can compose endometrial glands in female transplant recipients. Am J Obstet Gynecol. 2009 Dec;201(6):608.e1-8. doi: 10.1016/j.ajog.2009.07.026. Epub 2009 Oct 3.

Reference Type BACKGROUND
PMID: 19800602 (View on PubMed)

Taylor HS. Endometrial cells derived from donor stem cells in bone marrow transplant recipients. JAMA. 2004 Jul 7;292(1):81-5. doi: 10.1001/jama.292.1.81.

Reference Type BACKGROUND
PMID: 15238594 (View on PubMed)

Cervello I, Mas A, Gil-Sanchis C, Peris L, Faus A, Saunders PT, Critchley HO, Simon C. Reconstruction of endometrium from human endometrial side population cell lines. PLoS One. 2011;6(6):e21221. doi: 10.1371/journal.pone.0021221. Epub 2011 Jun 21.

Reference Type BACKGROUND
PMID: 21712999 (View on PubMed)

Nagori CB, Panchal SY, Patel H. Endometrial regeneration using autologous adult stem cells followed by conception by in vitro fertilization in a patient of severe Asherman's syndrome. J Hum Reprod Sci. 2011 Jan;4(1):43-8. doi: 10.4103/0974-1208.82360.

Reference Type BACKGROUND
PMID: 21772740 (View on PubMed)

March CM. Management of Asherman's syndrome. Reprod Biomed Online. 2011 Jul;23(1):63-76. doi: 10.1016/j.rbmo.2010.11.018. Epub 2010 Dec 4.

Reference Type BACKGROUND
PMID: 21549641 (View on PubMed)

Zhang X, Chen CH, Confino E, Barnes R, Milad M, Kazer RR. Increased endometrial thickness is associated with improved treatment outcome for selected patients undergoing in vitro fertilization-embryo transfer. Fertil Steril. 2005 Feb;83(2):336-40. doi: 10.1016/j.fertnstert.2004.09.020.

Reference Type BACKGROUND
PMID: 15705371 (View on PubMed)

Sanz-Ruiz R, Gutierrez Ibanes E, Arranz AV, Fernandez Santos ME, Fernandez PL, Fernandez-Aviles F. Phases I-III Clinical Trials Using Adult Stem Cells. Stem Cells Int. 2010 Nov 4;2010:579142. doi: 10.4061/2010/579142.

Reference Type BACKGROUND
PMID: 21076533 (View on PubMed)

Makela J, Anttila V, Ylitalo K, Takalo R, Lehtonen S, Makikallio T, Niemela E, Dahlbacka S, Tikkanen J, Kiviluoma K, Juvonen T, Lehenkari P. Acute homing of bone marrow-derived mononuclear cells in intramyocardial vs. intracoronary transplantation. Scand Cardiovasc J. 2009 Dec;43(6):366-73. doi: 10.1080/14017430903045350.

Reference Type BACKGROUND
PMID: 19544220 (View on PubMed)

Santamaria X, Cabanillas S, Cervello I, Arbona C, Raga F, Ferro J, Palmero J, Remohi J, Pellicer A, Simon C. Autologous cell therapy with CD133+ bone marrow-derived stem cells for refractory Asherman's syndrome and endometrial atrophy: a pilot cohort study. Hum Reprod. 2016 May;31(5):1087-96. doi: 10.1093/humrep/dew042. Epub 2016 Mar 22.

Reference Type DERIVED
PMID: 27005892 (View on PubMed)

Cervello I, Gil-Sanchis C, Santamaria X, Cabanillas S, Diaz A, Faus A, Pellicer A, Simon C. Human CD133(+) bone marrow-derived stem cells promote endometrial proliferation in a murine model of Asherman syndrome. Fertil Steril. 2015 Dec;104(6):1552-60.e1-3. doi: 10.1016/j.fertnstert.2015.08.032. Epub 2015 Sep 15.

Reference Type DERIVED
PMID: 26384164 (View on PubMed)

Other Identifiers

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1101-C-092-JS

Identifier Type: -

Identifier Source: org_study_id

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