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Miscarriage, RecurrentPhase 2/3NCT02706470

Use of Cyclosporin A for the Treatment of Recurrent Miscarriage

A Phase 2/3 study testing Cyclosporin A and Dydrogesterone in people with Miscarriage, Recurrent, run by Fudan University at 1 site in China.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 20 to 40 years, women only
Conditions the study is for
Miscarriage, Recurrent
What is being tested?
Cyclosporin A and Dydrogesterone
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
384 participants
Where
1 siteChina
Study dates
May 2016to Dec 2018
Phase
Phase 2/3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 20 to 40 years
  • Women only
  • No healthy volunteers
  • Adult

Who may be able to join

  • 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

Who cannot join

  • 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.

Trial locations and contacts

1 site in 1 country.

Jiangfeng Ye, MD contact

86-21-33189900 ext. 8386

jiangfeng_ye@hotmail.com

Meirong Du, MD contact

86-21-33189900 ext. 8386

dmrlq1973@sina.cn

China1 site

  • Obstetrics and Gynecology Hospital of Fudan University

    Shanghai, 200011

    Jiangfeng Ye, MD, 86-21-33189900 ext. 8386, jiangfeng_ye@hotmail.com

    Meirong Du, MD, 86-21-33189900 ext. 8386, dmrlq1973@sina.cn

Other trials in China

About this study

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

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.

Being tested
Cyclosporin A, Dydrogesterone
Keywords
recurrent miscarriage; immunology
Medical subject headings
Abortion, Habitual

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Cyclosporin ADrug

    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.

  • DydrogesteroneDrug

    Also called Duphaston

    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.

Study groups in NCT02706470
Study groupRoleWhat they receive
Cyclosporin AExperimentalPatients 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.
Receives: Drug: Cyclosporin A
DydrogesteroneActive comparatorPatients allocated to dydrogesterone group will receive oral dydrogesterone in a dose of 10 mg three times a day for 30 days in early pregnancy.
Receives: Drug: Dydrogesterone

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Live birth rate

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

    Measured: Up to 36 months

Secondary outcomes (5)

  1. 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.

    Measured: Up to 36 months

  2. 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.

    Measured: Up to 36 months

  3. 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.

    Measured: Up to 36 months

  4. Congenital malformations

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

    Measured: Up to 36 months

  5. Maternal outcomes: morbidity of infectious disease

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

    Measured: Up to 36 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Mar 2016 (estimated)
  2. Study startMay 2016
  3. Primary completionFeb 2018 (estimated)
  4. Study completionDec 2018 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
384 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02706470
Sponsor's protocol ID
2013SY034
Status last verified
Mar 2016
First submitted
2 Feb 2016
Last updated
15 Mar 2016
Results posted
No
Data monitoring committee
Yes
Individual data sharing
No

Publications

  • 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.

    PubMed 24817934

  • 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.

    PubMed 24133577

  • 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.

    PubMed 23028901

  • 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.

    PubMed 23410723

  • 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.

    PubMed 22848341

  • 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.

    PubMed 22766276

  • 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.

    PubMed 22495096

  • 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.

    PubMed 18322274

  • 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.

    PubMed 18299432

  • 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.

    PubMed 17636278

  • 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.

    PubMed 17566014

  • 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.

    PubMed 17229932

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing Cyclosporin A and Dydrogesterone in people with Miscarriage, Recurrent, run by Fudan University at 1 site in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 15 Mar 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Jiangfeng Ye, MD (86-21-33189900 ext. 8386, jiangfeng_ye@hotmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Live birth rate (time frame: Up to 36 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02706470, which also lists 12 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Mar 2016.

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