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

Asherman's Syndrome Clinical Trial

— BMSCT  

Official title:

New Therapeutic Approaches to Treat Asherman's Syndrome and Endometrial Atrophy Based in BM Stem Cells Autologous Transplantation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02144987
• Other study ID #: 1101-C-092-JS
• Status: Completed
• Phase: Phase 4
• First received: May 19, 2014
• Last updated: April 21, 2015
• Start date: April 2013
• Est. completion date: September 2014

Study information

• Verified date: April 2015
• Source: Instituto Valenciano de Infertilidad, IVI VALENCIA
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Comité Ético de Investigación ClínicaSpain: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: September 2014
• Est. primary completion date: September 2014
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 45 Years

Eligibility

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

• ß-hCG negative

• Absence of SDT

Exclusion Criteria:

• Absence of peripheral vein access

• Lack of accomplish inclusion criteria

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Asherman's Syndrome
• Atrophy
• Endometrium; Atrophy, Cervix
• Syndrome

Intervention

Biological:
• Bone Marrow CD133+ Stem Cell Transplantation
Bone Marrow Stem Cell (BMSC) mobilization peripheral blood induced by granulocyte-CSF (G-CSF) 5 mcg/kg sc every 12 hours for 4 days. 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. CD133+ cells transplantation into the uterine spiral arterioles by intra-arterial catheterization Subsequently Hormonal Replacement Therapy (HRT) will be given to the patients Hysteroscopy will be performed 2-3 months after stem cell transplantation Embryo transfer will be performed 3-6 months after stem cell transplantation with HRT endometrial preparation

Locations

Country	Name	City	State
Spain	Hospital Clinico y Universitario de Valencia	Valencia
Spain	Instituto Valenciano Infertilidad	Valencia

Sponsors (2)

Lead Sponsor	Collaborator
Instituto Valenciano de Infertilidad, IVI VALENCIA	Fundación para la Investigación del Hospital Clínico de Valencia

Country where clinical trial is conducted

Spain, 

References & Publications (10)

Cervelló I, Gil-Sanchis C, Mas A, Faus A, Sanz J, Moscardó F, Higueras G, Sanz MA, Pellicer A, Simón 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. — View Citation

Cervelló I, Mas A, Gil-Sanchis C, Peris L, Faus A, Saunders PT, Critchley HO, Simón 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. — View Citation

Chan RW, Schwab KE, Gargett CE. Clonogenicity of human endometrial epithelial and stromal cells. Biol Reprod. 2004 Jun;70(6):1738-50. Epub 2004 Feb 6. — View Citation

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. — View Citation

Mäkelä J, Anttila V, Ylitalo K, Takalo R, Lehtonen S, Mäkikallio T, Niemelä 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. — View Citation

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. Review. — View Citation

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. — View Citation

Sanz-Ruiz R, Gutiérrez Ibañes E, Arranz AV, Fernández Santos ME, Fernández PL, Fernández-Avilés F. Phases I-III Clinical Trials Using Adult Stem Cells. Stem Cells Int. 2010 Nov 4;2010:579142. doi: 10.4061/2010/579142. — View Citation

Taylor HS. Endometrial cells derived from donor stem cells in bone marrow transplant recipients. JAMA. 2004 Jul 7;292(1):81-5. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Live-birth rate	Live birth rate is the percentage of all cycles that lead to live birth, and is the pregnancy rate adjusted for miscarriages and stillbirths.	15 months	No
Primary	Ongoing pregnancy rate	Ongoing pregnancy rate is the percentage of all cycles that lead to presence of heartbeat in Ultrasound scan at the end of the first trimester	9 months	No
Primary	Implantation Rate	Implantation rate is the percentage of embryos which successfully undergo implantation compared to the number of embryos transferred in a given period.	6 months	No
Secondary	Endometrial thickness prior to the treatment	Endometrial thickness measured with Ultrasound in a previous treatment with Hormonal Replacement Therapy	0	No
Secondary	Endometrial Thickness after treatment	Endometrial thickness measured with Ultrasound with Hormonal Replacement Therapy 3-6 months after Bone Marrow Stem Cell Transplantation	3-6 months	No