Immunomodulatory Effects of IVIg on Pregnancy Rate of Patient With Recurrent Pregnancy Loss
Primary Purpose
Recurrent Pregnancy Loss
Status
Completed
Phase
Phase 2
Locations
Iran, Islamic Republic of
Study Type
Interventional
Intervention
IVIg
Sponsored by
About this trial
This is an interventional treatment trial for Recurrent Pregnancy Loss focused on measuring Recurrent Pregnancy Loss, IVIg, Pregnancy Rate
Eligibility Criteria
Inclusion Criteria:
- 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
Exclusion Criteria:
- Our criteria for exclusion of patients from the study include the following:
- 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.
Sites / Locations
- Alzahra hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
No Intervention
Arm Label
Treatment group
control group
Arm Description
IVIg group
Patients who do not receive any treatment despite a history of Recurrent Pregnancy Loss problem as controls
Outcomes
Primary Outcome Measures
Changes in NK cells, T reg and Th17 cells frequency.
Flowcytometry
Changes in secretion levels of cytokines related to Treg and Th17 cells(IL-17,IL-21)
Elisa
Changes in exoression of cytokines gene.
RT pcr
Secondary Outcome Measures
Ongoing pregnancy rate in patients with Recurrent Pregnancy Loss (RPL)
by sonography
Live berth rate in patients with Recurrent Pregnancy Loss (RPL).
Monitoring by gynecologists
Full Information
NCT ID
NCT03174951
First Posted
May 28, 2017
Last Updated
September 13, 2018
Sponsor
Tabriz University of Medical Sciences
1. Study Identification
Unique Protocol Identification Number
NCT03174951
Brief Title
Immunomodulatory Effects of IVIg on Pregnancy Rate of Patient With Recurrent Pregnancy Loss
Official Title
Effect of IVIg on Pregnancy Rate of Patient With Recurrent Pregnancy Loss With Immunological Causes
Study Type
Interventional
2. Study Status
Record Verification Date
May 2017
Overall Recruitment Status
Completed
Study Start Date
September 20, 2016 (Actual)
Primary Completion Date
March 10, 2017 (Actual)
Study Completion Date
June 20, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Tabriz University of Medical Sciences
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Recurrent Pregnancy Loss
Keywords
Recurrent Pregnancy Loss, IVIg, Pregnancy Rate
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
50 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Treatment group
Arm Type
Experimental
Arm Description
IVIg group
Arm Title
control group
Arm Type
No Intervention
Arm Description
Patients who do not receive any treatment despite a history of Recurrent Pregnancy Loss problem as controls
Intervention Type
Drug
Intervention Name(s)
IVIg
Intervention Description
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.
Primary Outcome Measure Information:
Title
Changes in NK cells, T reg and Th17 cells frequency.
Description
Flowcytometry
Time Frame
up to 8 month of pregnancy
Title
Changes in secretion levels of cytokines related to Treg and Th17 cells(IL-17,IL-21)
Description
Elisa
Time Frame
up to 8 month of pregnancy
Title
Changes in exoression of cytokines gene.
Description
RT pcr
Time Frame
up to 8 month of pregnancy
Secondary Outcome Measure Information:
Title
Ongoing pregnancy rate in patients with Recurrent Pregnancy Loss (RPL)
Description
by sonography
Time Frame
up to 8 month of pregnancy
Title
Live berth rate in patients with Recurrent Pregnancy Loss (RPL).
Description
Monitoring by gynecologists
Time Frame
up to 1 year
10. Eligibility
Sex
Female
Gender Based
Yes
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
41 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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
Exclusion Criteria:
- Our criteria for exclusion of patients from the study include the following:
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mohammad Nouri, Ph.D
Organizational Affiliation
Head of SCARM institute
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Mehdi Yousefi, Immunologist
Organizational Affiliation
SCARM institute
Official's Role
Study Director
Facility Information:
Facility Name
Alzahra hospital
City
Tabriz
Country
Iran, Islamic Republic of
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
22889462
Citation
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.
Results Reference
result
PubMed Identifier
19710204
Citation
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.
Results Reference
result
PubMed Identifier
19819893
Citation
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.
Results Reference
result
PubMed Identifier
24628478
Citation
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.
Results Reference
result
PubMed Identifier
12765346
Citation
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.
Results Reference
result
PubMed Identifier
17166218
Citation
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.
Results Reference
result
PubMed Identifier
21095154
Citation
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.
Results Reference
result
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Immunomodulatory Effects of IVIg on Pregnancy Rate of Patient With Recurrent Pregnancy Loss
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