Back to results

Use of Cyclosporin A for the Treatment of Recurrent Miscarriage

Primary Purpose

Miscarriage, Recurrent

Status

Unknown status

Phase

Phase 2

Locations

China

Study Type

Interventional

Intervention

Cyclosporin A

Dydrogesterone

About this trial

This is an interventional treatment trial for Miscarriage, Recurrent focused on measuring recurrent miscarriage; immunology

Eligibility Criteria

20 Years - 40 Years (Adult)FemaleDoes not accept healthy volunteers

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.

Sites / Locations

Obstetrics and Gynecology Hospital of Fudan University

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Cyclosporin A

Dydrogesterone

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Live birth rate

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

Secondary Outcome Measures

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

The difference in the rates of miscarriage (pregnancy loss before 20 weeks gestation) between patients assigned oral CsA and Dydrogesterone.

Fetal death

The difference in the rates of fetal death (fetal death after 20 weeks of gestational age) between patients assigned oral CsA and Dydrogesterone.

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

The difference in the rates of premature delivery (deliveries with gestational age less than 37 weeks) between patients assigned oral CsA and Dydrogesterone.

Congenital malformations

The difference in the rates of congenital malformations between patients assigned oral CsA and Dydrogesterone.

Maternal outcomes: morbidity of infectious disease

The difference of morbidity of infectious disease in pregnancy between two arms.

Full Information

NCT ID

NCT02706470

First Posted

February 2, 2016

Last Updated

March 12, 2016

Sponsor

Fudan University

1. Study Identification

Unique Protocol Identification Number

NCT02706470

Brief Title

Use of Cyclosporin A for the Treatment of Recurrent Miscarriage

Official Title

A Randomized, Controlled Trial of Cyclosporin A for Women With Unexplained Recurrent Miscarriage

Study Type

Interventional

2. Study Status

Record Verification Date

March 2016

Overall Recruitment Status

Unknown status

Study Start Date

May 2016 (undefined)

Primary Completion Date

February 2018 (Anticipated)

Study Completion Date

December 2018 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Fudan University

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Miscarriage, Recurrent

Keywords

recurrent miscarriage; immunology

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2, Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

384 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Cyclosporin A

Arm Type

Experimental

Arm Description

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.

Arm Title

Dydrogesterone

Arm Type

Active Comparator

Arm Description

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.

Intervention Type

Drug

Intervention Name(s)

Cyclosporin A

Intervention Description

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

Intervention Name(s)

Dydrogesterone

Other Intervention Name(s)

Duphaston

Intervention Description

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.

Primary Outcome Measure Information:

Title

Live birth rate

Description

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

Time Frame

Up to 36 months

Secondary Outcome Measure Information:

Title

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

Description

The difference in the rates of miscarriage (pregnancy loss before 20 weeks gestation) between patients assigned oral CsA and Dydrogesterone.

Time Frame

Up to 36 months

Title

Fetal death

Description

The difference in the rates of fetal death (fetal death after 20 weeks of gestational age) between patients assigned oral CsA and Dydrogesterone.

Time Frame

Up to 36 months

Title

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

Description

The difference in the rates of premature delivery (deliveries with gestational age less than 37 weeks) between patients assigned oral CsA and Dydrogesterone.

Time Frame

Up to 36 months

Title

Congenital malformations

Description

The difference in the rates of congenital malformations between patients assigned oral CsA and Dydrogesterone.

Time Frame

Up to 36 months

Title

Maternal outcomes: morbidity of infectious disease

Description

The difference of morbidity of infectious disease in pregnancy between two arms.

Time Frame

Up to 36 months

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

20 Years

Maximum Age & Unit of Time

40 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Jiangfeng Ye, MD

Phone

86-21-33189900

Ext

8386

jiangfeng_ye@hotmail.com

First Name & Middle Initial & Last Name or Official Title & Degree

Meirong Du, MD

Phone

86-21-33189900

Ext

8386

dmrlq1973@sina.cn

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Dajin Li, MD

Organizational Affiliation

Obstetrics & Gynecology Hospital of Fudan University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Obstetrics and Gynecology Hospital of Fudan University

City

Shanghai

ZIP/Postal Code

200011

Country

China

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Jiangfeng Ye, MD

Phone

86-21-33189900

Ext

8386

jiangfeng_ye@hotmail.com

First Name & Middle Initial & Last Name & Degree

Meirong Du, MD

Phone

86-21-33189900

Ext

8386

dmrlq1973@sina.cn

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

24817934

Citation

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.

Results Reference

background

PubMed Identifier

24133577

Citation

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.

Results Reference

background

PubMed Identifier

23028901

Citation

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.

Results Reference

background

PubMed Identifier

23410723

Citation

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.

Results Reference

background

PubMed Identifier

22848341

Citation

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.

Results Reference

background

PubMed Identifier

22766276

Citation

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.

Results Reference

background

PubMed Identifier

22495096

Citation

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.

Results Reference

background

PubMed Identifier

18322274

Citation

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.

Results Reference

background

PubMed Identifier

18299432

Citation

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.

Results Reference

background

PubMed Identifier

17636278

Citation

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.

Results Reference

background

PubMed Identifier

17566014

Citation

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.

Results Reference

background

PubMed Identifier

17229932

Citation

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.

Results Reference

background

Learn more about this trial

Use of Cyclosporin A for the Treatment of Recurrent Miscarriage

We'll reach out to this number within 24 hrs