Use of Cyclosporin A for the Treatment of Recurrent Miscarriage

NCT02706470 | Unknown Phase 2 DMC

• 1 other identifier: 2013SY034
• Study Type: interventional
• Target: 384
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine whether Cyclosporin A (CsA) - an immunosuppressant drug - in early pregnancy will reduce the risk of miscarriage in women who had a history of unexplained recurrent miscarriages, as compared with that treated with Dydrogesterone-an active comparator. The hypothesis is based on the evidence found in vitro and in vivo experiments that CsA can induce maternal-fetal tolerance so that it may reduce the risk of miscarriage.

Conditions

Miscarriage, Recurrent

Keywords

recurrent miscarriage; immunology

Outcome Measures

Primary Outcomes (1)

• Live birth rate

  The difference in the live birth rates between patients with recurrent miscarriage assigned oral CsA and Dydrogesterone.

  Up to 36 months

Secondary Outcomes (5)

• The difference in the rate of miscarriage between patients with recurrent miscarriage treated with CsA and Dydrogesterone.

  Up to 36 months

• Fetal death

  Up to 36 months

• The difference in the rate of premature delivery between patients treated with CsA and Dydrogesterone.

  Up to 36 months

• Congenital malformations

  Up to 36 months

• Maternal outcomes: morbidity of infectious disease

  Up to 36 months

Study Arms (2)

Cyclosporin A

EXPERIMENTAL

Patients allocated to Cyclosporin A group will receive oral Cyclosporin A in a dose of 50 mg three times a day for 20-30 days in early pregnancy.

Drug: Cyclosporin A

Dydrogesterone

ACTIVE COMPARATOR

Patients allocated to dydrogesterone group will receive oral dydrogesterone in a dose of 10 mg three times a day for 30 days in early pregnancy.

Drug: Dydrogesterone

Interventions

Cyclosporin A DRUG

Patients will receive oral CsA in a dose of 50mg three times a day for 20-30 days since the occurrence of positive result in human chorionic gonadotropin (HCG) test in urine and 14 consecutive days of elevated basal body temperature. The dosage of CsA will be adjusted according to baseline and peak value of CsA blood concentration. If the baseline blood concentration of CsA is lower than 40ng/ml or the peak blood concentration of CsA is lower than 500ng/ml, the dosage of CsA will be increased to 75 mg three times a day.

Cyclosporin A

Dydrogesterone DRUG

Patients will receive oral dydrogesterone 10 mg three times a day for 30 days since the occurrence of positive result in HCG test in urine and 14 consecutive days of elevated basal body temperature.

Also known as: Duphaston

Dydrogesterone

Eligibility Criteria

• Age: 20 Years - 40 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Both the woman and her husband agree to participate and sign the informed consent form.
• Have a history of two or more unexplained recurrent miscarriages.
• Spontaneous conception.
• Gestational age less than 5 weeks.
• Have a normal menstrual cycle (\>=23 and \<=35 days) and biphasic pattern of basal body temperature before pregnancy.
• No significant chromosomal aberrations in the couple.
• Semen quality tests show not apparent abnormalities in husband

You may not qualify if:

• Age below 18 or above 41 years at conception.
• Present pregnancy is a result of donor insemination or egg donation.
• Significant uterine anomalies detected by ultrasonography, hysterosalpingography, or hysteroscopy.
• Contraindications of CsA (e.g. severe infectious diseases, tumor or immunodeficiency) or Dydrogesterone.
• Smoking more than 20 daily.

Sponsors & Collaborators

• Fudan University: lead

Study Sites (1)

Obstetrics and Gynecology Hospital of Fudan University

Shanghai, 200011, China

Location

Related Publications (12)

• Huang YH, Ma YL, Ma L, Mao JL, Zhang Y, Du MR, Li DJ. Cyclosporine A improves adhesion and invasion of mouse preimplantation embryos via upregulating integrin beta3 and matrix metalloproteinase-9. Int J Clin Exp Pathol. 2014 Mar 15;7(4):1379-88. eCollection 2014.

  PMID: 24817934 BACKGROUND

• Wang SC, Yu M, Li YH, Piao HL, Tang CL, Sun C, Zhu R, Li MQ, Jin LP, Li DJ, Du MR. Cyclosporin A promotes proliferating cell nuclear antigen expression and migration of human cytotrophoblast cells via the mitgen-activated protein kinase-3/1-mediated nuclear factor-kappaB signaling pathways. Int J Clin Exp Pathol. 2013 Sep 15;6(10):1999-2010. eCollection 2013.

  PMID: 24133577 BACKGROUND

• Piao HL, Wang SC, Tao Y, Zhu R, Sun C, Fu Q, Du MR, Li DJ. Cyclosporine A enhances Th2 bias at the maternal-fetal interface in early human pregnancy with aid of the interaction between maternal and fetal cells. PLoS One. 2012;7(9):e45275. doi: 10.1371/journal.pone.0045275. Epub 2012 Sep 27.

  PMID: 23028901 BACKGROUND

• Wang SC, Tang ChL, Piao HL, Zhu R, Sun Ch, Tao Y, Fu Q, Li DJ, Du MR. Cyclosporine A promotes in vitro migration of human first-trimester trophoblasts via MAPK/ERK1/2-mediated NF-kappaB and Ca2+/calcineurin/NFAT signaling. Placenta. 2013 Apr;34(4):374-80. doi: 10.1016/j.placenta.2013.01.009. Epub 2013 Feb 11.

  PMID: 23410723 BACKGROUND

• Zhao HB, Tang CL, Hou YL, Xue LR, Li MQ, Du MR, Li DJ. CXCL12/CXCR4 axis triggers the activation of EGF receptor and ERK signaling pathway in CsA-induced proliferation of human trophoblast cells. PLoS One. 2012;7(7):e38375. doi: 10.1371/journal.pone.0038375. Epub 2012 Jul 27.

  PMID: 22848341 BACKGROUND

• Tang CL, Zhao HB, Li MQ, Du MR, Meng YH, Li DJ. Focal adhesion kinase signaling is necessary for the Cyclosporin A-enhanced migration and invasion of human trophoblast cells. Placenta. 2012 Sep;33(9):704-11. doi: 10.1016/j.placenta.2012.06.007. Epub 2012 Jul 4.

  PMID: 22766276 BACKGROUND

• Du MR, Zhou WH, Piao HL, Li MQ, Tang CL, Li DJ. Cyclosporin A promotes crosstalk between human cytotrophoblast and decidual stromal cell through up-regulating CXCL12/CXCR4 interaction. Hum Reprod. 2012 Jul;27(7):1955-65. doi: 10.1093/humrep/des111. Epub 2012 Apr 11.

  PMID: 22495096 BACKGROUND

• Du MR, Zhou WH, Dong L, Zhu XY, He YY, Yang JY, Li DJ. Cyclosporin A promotes growth and invasiveness in vitro of human first-trimester trophoblast cells via MAPK3/MAPK1-mediated AP1 and Ca2+/calcineurin/NFAT signaling pathways. Biol Reprod. 2008 Jun;78(6):1102-10. doi: 10.1095/biolreprod.107.063503. Epub 2008 Mar 5.

  PMID: 18322274 BACKGROUND

• Zhou WH, Dong L, Du MR, Zhu XY, Li DJ. Cyclosporin A improves murine pregnancy outcome in abortion-prone matings: involvement of CD80/86 and CD28/CTLA-4. Reproduction. 2008 Mar;135(3):385-95. doi: 10.1530/REP-07-0063.

  PMID: 18299432 BACKGROUND

• Du MR, Zhou WH, Yan FT, Zhu XY, He YY, Yang JY, Li DJ. Cyclosporine A induces titin expression via MAPK/ERK signalling and improves proliferative and invasive potential of human trophoblast cells. Hum Reprod. 2007 Sep;22(9):2528-37. doi: 10.1093/humrep/dem222. Epub 2007 Jul 18.

  PMID: 17636278 BACKGROUND

• Zhou WH, Du MR, Dong L, Zhu XY, Yang JY, He YY, Li DJ. Cyclosporin A increases expression of matrix metalloproteinase 9 and 2 and invasiveness in vitro of the first-trimester human trophoblast cells via the mitogen-activated protein kinase pathway. Hum Reprod. 2007 Oct;22(10):2743-50. doi: 10.1093/humrep/dem097. Epub 2007 Jun 12.

  PMID: 17566014 BACKGROUND

• Du MR, Dong L, Zhou WH, Yan FT, Li DJ. Cyclosporin a improves pregnancy outcome by promoting functions of trophoblasts and inducing maternal tolerance to the allogeneic fetus in abortion-prone matings in the mouse. Biol Reprod. 2007 May;76(5):906-14. doi: 10.1095/biolreprod.106.056648. Epub 2007 Jan 17.

  PMID: 17229932 BACKGROUND

MeSH Terms

Conditions

Abortion, Habitual

Interventions

Cyclosporine; Dydrogesterone

Condition Hierarchy (Ancestors)

Abortion, Spontaneous; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Intervention Hierarchy (Ancestors)

Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds

Study Officials

• Dajin Li, MD

  Obstetrics & Gynecology Hospital of Fudan University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jiangfeng Ye, MD

CONTACT

86-21-33189900; jiangfeng_ye@hotmail.com

Meirong Du, MD

CONTACT

86-21-33189900; dmrlq1973@sina.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: February 2, 2016
• First Posted: March 11, 2016
• Study Start: May 1, 2016
• Primary Completion: February 1, 2018
• Study Completion: December 1, 2018
• Last Updated: March 15, 2016

Record last verified: 2016-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)