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

NCT02144987 | Completed Phase 4

• 1 other identifier: 1101-C-092-JS
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Asherman's Syndrome; Endometrium; Atrophy, Cervix

Outcome Measures

Primary Outcomes (3)

• 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

• 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

• 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

Secondary Outcomes (2)

• Endometrial thickness prior to the treatment

  0

• Endometrial Thickness after treatment

  3-6 months

Interventions

Bone Marrow CD133+ Stem Cell Transplantation BIOLOGICAL

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

Also known as: Neupogen

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• Absence of peripheral vein access

Sponsors & Collaborators

• Instituto Valenciano de Infertilidad, IVI VALENCIA: lead
• Fundación para la Investigación del Hospital Clínico de Valencia: collaborator

Study Sites (2)

Hospital Clinico y Universitario de Valencia

Valencia, Valencia, 46010, Spain

Location

Instituto Valenciano Infertilidad

Valencia, Valencia, 46015, Spain

Location

Related Publications (12)

• 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.

  PMID: 14766732 BACKGROUND

• 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.

  PMID: 22276168 BACKGROUND

• 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.

  PMID: 19800602 BACKGROUND

• 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.

  PMID: 15238594 BACKGROUND

• 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.

  PMID: 21712999 BACKGROUND

• 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.

  PMID: 21772740 BACKGROUND

• 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.

  PMID: 21549641 BACKGROUND

• 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.

  PMID: 15705371 BACKGROUND

• 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.

  PMID: 21076533 BACKGROUND

• 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.

  PMID: 19544220 BACKGROUND

• 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.

  PMID: 27005892 DERIVED

• 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.

  PMID: 26384164 DERIVED

MeSH Terms

Conditions

Gynatresia; Atrophy

Interventions

Filgrastim

Condition Hierarchy (Ancestors)

Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Granulocyte Colony-Stimulating Factor; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• Xavier Santamaria, MD, PhD

  Instituto Valenciano Infertilidad

  PRINCIPAL INVESTIGATOR

• Carlos Simon, MD, PhD

  Instituto Valenciano Infertilidad

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 19, 2014
• First Posted: May 22, 2014
• Study Start: April 1, 2013
• Primary Completion: September 1, 2014
• Study Completion: September 1, 2014
• Last Updated: April 22, 2015

Record last verified: 2015-04

Locations

ES (2)