Use of Cyclosporin A for the Treatment of Recurrent Miscarriage

NCT ID: NCT02706470

Last Updated: 2016-03-15

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

UNKNOWN

Clinical Phase

PHASE2/PHASE3

Total Enrollment

384 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-05-31

Study Completion Date

2018-12-31

Brief Summary

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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.

Detailed Description

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Conditions

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Miscarriage, Recurrent

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Cyclosporin A

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.

Group Type EXPERIMENTAL

Cyclosporin A

Intervention Type 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.

Dydrogesterone

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.

Group Type ACTIVE_COMPARATOR

Dydrogesterone

Intervention Type 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.

Interventions

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Cyclosporin A

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.

Intervention Type DRUG

Dydrogesterone

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.

Intervention Type DRUG

Other Intervention Names

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Duphaston

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* 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.
Minimum Eligible Age

20 Years

Maximum Eligible Age

40 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Fudan University

OTHER

Sponsor Role lead

Responsible Party

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Jiangfeng Ye

MD

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Dajin Li, MD

Role: PRINCIPAL_INVESTIGATOR

Obstetrics & Gynecology Hospital of Fudan University

Locations

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Obstetrics and Gynecology Hospital of Fudan University

Shanghai, , China

Site Status

Countries

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China

Central Contacts

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Jiangfeng Ye, MD

Role: CONTACT

86-21-33189900 ext. 8386

Meirong Du, MD

Role: CONTACT

86-21-33189900 ext. 8386

Facility Contacts

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Jiangfeng Ye, MD

Role: primary

86-21-33189900 ext. 8386

Meirong Du, MD

Role: backup

86-21-33189900 ext. 8386

References

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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.

Reference Type BACKGROUND
PMID: 24817934 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24133577 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23028901 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23410723 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22848341 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22766276 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22495096 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18322274 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18299432 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17636278 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17566014 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17229932 (View on PubMed)

Other Identifiers

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2013SY034

Identifier Type: -

Identifier Source: org_study_id

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