Immunomodulatory Effects of IVIg on Pregnancy Rate of Patient With Recurrent Pregnancy Loss

NCT03174951 | Completed Phase 2 DMC

• 1 other identifier: TabrizUMS-infertility-003
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

Miscarriage occurs in about 1-2% of human pregnancies and is one of the common pregnancy problems before 12 weeks of pregnancy. Anatomical and chromosomal abnormalities, microbial factors and auto and alloimmune reactions have been speculated to attribute in recurrent miscarriage. Unexplained recurrent miscarriage (URM) is defined as three or more repeated abortions, probably caused by maternal immunological rejection . Given that maternal immune system encounters semi-allogeneic fetus, pregnancy outcome is associated with the interaction between maternal immune system and immuno-regulatory capability of the fetus. Effectiveness of treatment approaches in RM patients has been controversial and remained to be discovered. Immunomodulatory agents such as corticosteroids and allogeneic lymphocyte immunization showed variable success rates in RM patients. Therapeutic effects of IVIG in unexplained RM is controversial and most positive results were obtained from the trials in RM women with cellular immune abnormalities, such as increased NK cell level and/or cytotoxicity, and T cell abnormalities. Previous studies have shown that the incidence of genetic abnormalities in children who have received immunosuppressive drugs such as IVIg like normal people and normal society. In this study we used IVIg at the time of positive pregnancy,400 mg/kg IVIG was administered intravenously. Following the first administration, IVIG well given every 4 weeks through 32 weeks of gestation to suppress the immune system in patients with immunological causes of RPL and the results will be compared with a control group that did not receive any type of drug.

Conditions

Recurrent Pregnancy Loss

Keywords

Recurrent Pregnancy Loss; IVIg; Pregnancy Rate

Outcome Measures

Primary Outcomes (3)

• Changes in NK cells, T reg and Th17 cells frequency.

  Flowcytometry

  up to 8 month of pregnancy

• Changes in secretion levels of cytokines related to Treg and Th17 cells(IL-17,IL-21)

  Elisa

  up to 8 month of pregnancy

• Changes in exoression of cytokines gene.

  RT pcr

  up to 8 month of pregnancy

Secondary Outcomes (2)

• Ongoing pregnancy rate in patients with Recurrent Pregnancy Loss (RPL)

  up to 8 month of pregnancy

• Live berth rate in patients with Recurrent Pregnancy Loss (RPL).

  up to 1 year

Study Arms (2)

Treatment group

EXPERIMENTAL

IVIg group

Drug: IVIg

control group

NO INTERVENTION

Patients who do not receive any treatment despite a history of Recurrent Pregnancy Loss problem as controls

Interventions

IVIg DRUG

Patients will take 400mg/kg IVIg at the time of positive pregnancy,Following the first administration, IVIG well given every 4 weeks through 32 weeks of gestation.

Treatment group

Eligibility Criteria

• Age: 18 Years - 41 Years
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Enrolled patients will experience at least 3 times recurrent pregnancy loss.
• Patients dont have history of any type of immunotherapy.
• Patients must have abnormal NK cell or NK cell cytotoxicity or Th1/Th2 ratio

You may not qualify if:

• Patients or their spouse has abnormal karyotype or chromosomal and genetically disorders.
• Patients who have bleeding problems.
• Patients who have chronic disorders those are forced to use the specific drug.
• Patients who have positive test for HIV, HCV or HBV infection.
• Patients who have a history of asthma and allergies.
• Patients who have uterus abnormalities.

Sponsors & Collaborators

• Tabriz University of Medical Sciences: lead

Study Sites (1)

Alzahra hospital

Tabriz, Iran

Location

Related Publications (7)

• Sugiura-Ogasawara M, Suzuki S, Ozaki Y, Katano K, Suzumori N, Kitaori T. Frequency of recurrent spontaneous abortion and its influence on further marital relationship and illness: the Okazaki Cohort Study in Japan. J Obstet Gynaecol Res. 2013 Jan;39(1):126-31. doi: 10.1111/j.1447-0756.2012.01973.x. Epub 2012 Aug 13.

  PMID: 22889462 RESULT

• Santos MA, Kuijk EW, Macklon NS. The impact of ovarian stimulation for IVF on the developing embryo. Reproduction. 2010 Jan;139(1):23-34. doi: 10.1530/REP-09-0187.

  PMID: 19710204 RESULT

• King K, Smith S, Chapman M, Sacks G. Detailed analysis of peripheral blood natural killer (NK) cells in women with recurrent miscarriage. Hum Reprod. 2010 Jan;25(1):52-8. doi: 10.1093/humrep/dep349. Epub 2009 Oct 9.

  PMID: 19819893 RESULT

• Goring SM, Levy AR, Ghement I, Kalsekar A, Eyawo O, L'Italien GJ, Kasiske B. A network meta-analysis of the efficacy of belatacept, cyclosporine and tacrolimus for immunosuppression therapy in adult renal transplant recipients. Curr Med Res Opin. 2014 Aug;30(8):1473-87. doi: 10.1185/03007995.2014.898140. Epub 2014 Apr 3.

  PMID: 24628478 RESULT

• Yamada H, Morikawa M, Furuta I, Kato EH, Shimada S, Iwabuchi K, Minakami H. Intravenous immunoglobulin treatment in women with recurrent abortions: increased cytokine levels and reduced Th1/Th2 lymphocyte ratio in peripheral blood. Am J Reprod Immunol. 2003 Feb;49(2):84-9. doi: 10.1034/j.1600-0897.2003.01184.x.

  PMID: 12765346 RESULT

• Hutton B, Sharma R, Fergusson D, Tinmouth A, Hebert P, Jamieson J, Walker M. Use of intravenous immunoglobulin for treatment of recurrent miscarriage: a systematic review. BJOG. 2007 Feb;114(2):134-42. doi: 10.1111/j.1471-0528.2006.01201.x. Epub 2006 Dec 12.

  PMID: 17166218 RESULT

• Kolls JK, Khader SA. The role of Th17 cytokines in primary mucosal immunity. Cytokine Growth Factor Rev. 2010 Dec;21(6):443-8. doi: 10.1016/j.cytogfr.2010.11.002. Epub 2010 Nov 20.

  PMID: 21095154 RESULT

MeSH Terms

Interventions

Immunoglobulins, Intravenous

Intervention Hierarchy (Ancestors)

Immunoglobulin G; Immunoglobulin Isotypes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Mohammad Nouri, Ph.D

  Head of SCARM institute

  STUDY CHAIR

• Mehdi Yousefi, Immunologist

  SCARM institute

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 28, 2017
• First Posted: June 5, 2017
• Study Start: September 20, 2016
• Primary Completion: March 10, 2017
• Study Completion: June 20, 2017
• Last Updated: September 17, 2018

Record last verified: 2017-05

Data Sharing

• IPD Sharing: Will not share

Locations

IR (1)