Recurrent Pregnancy LossPhase 2NCT03174951
Immunomodulatory Effects of IVIg on Pregnancy Rate of Patient With Recurrent Pregnancy Loss
A Phase 2 study testing IVIg in people with Recurrent Pregnancy Loss, run by Tabriz University of Medical Sciences at 1 site in Iran.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 41 years, women only
- Conditions the study is for
- Recurrent Pregnancy Loss
- What is being tested?
- IVIg
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteIran
- Study dates
- 20 Sep 2016to 20 Jun 2017
- Phase
- Phase 2
- 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 18 to 41 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- 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
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effect of IVIg on Pregnancy Rate of Patient With Recurrent Pregnancy Loss With Immunological Causes
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
- Being tested
- IVIg
- Keywords
- Recurrent Pregnancy Loss, IVIg, Pregnancy Rate
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IVIgDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Treatment group | Experimental | IVIg group Receives: Drug: IVIg |
| control group | No intervention | Patients who do not receive any treatment despite a history of Recurrent Pregnancy Loss problem as controls |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in NK cells, T reg and Th17 cells frequency.
Flowcytometry
Measured: up to 8 month of pregnancy
Changes in secretion levels of cytokines related to Treg and Th17 cells(IL-17,IL-21)
Elisa
Measured: up to 8 month of pregnancy
Changes in exoression of cytokines gene.
RT pcr
Measured: up to 8 month of pregnancy
Secondary outcomes (2)
Ongoing pregnancy rate in patients with Recurrent Pregnancy Loss (RPL)
by sonography
Measured: up to 8 month of pregnancy
Live berth rate in patients with Recurrent Pregnancy Loss (RPL).
Monitoring by gynecologists
Measured: up to 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jun 2017
- Study start20 Sep 2016
- Primary completion10 Mar 2017
- Study completion20 Jun 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Recurrent Pregnancy LossStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tabriz University of Medical Sciences
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Mohammad Nouri, Ph.D, Study chair, Head of SCARM instituteMehdi Yousefi, Immunologist, Study director, SCARM institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03174951
- Sponsor's protocol ID
- TabrizUMS-infertility-003
- Status last verified
- May 2017
- First submitted
- 28 May 2017
- Last updated
- 17 Sep 2018
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 22889462Santos 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.
PubMed 19710204King 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.
PubMed 19819893Goring 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.
PubMed 24628478Yamada 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.
PubMed 12765346Hutton 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.
PubMed 17166218Kolls 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.
PubMed 21095154
Study at a glance
From the registry record, last updated by the sponsor on 17 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of IVIg on Pregnancy Rate of Patient With Recurrent Pregnancy Loss With Immunological Causes
- ClinicalTrials.gov ID
- NCT03174951
- Acronym / sponsor ID
- TabrizUMS-infertility-003
- Conditions
- Recurrent Pregnancy Loss
- Keywords
- Recurrent Pregnancy Loss, IVIg, Pregnancy Rate
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- Tabriz University of Medical SciencesUniversity, hospital or other
- Study start
- 20 Sep 2016 (actual)
- Primary completion
- 10 Mar 2017 (actual)
- Study completion
- 20 Jun 2017 (actual)
- First posted
- 5 Jun 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Treatment group | Experimental | Drug: IVIgIVIg group |
| control group | No intervention | –Patients who do not receive any treatment despite a history of Recurrent Pregnancy Loss problem as controls |
Who may qualify
- Ages
- 18 to 41 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (7 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IVIgPatients 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. | Drug | Treatment group |
Primary outcome
Changes in NK cells, T reg and Th17 cells frequency.
Time frame: up to 8 month of pregnancy
Flowcytometry
Changes in secretion levels of cytokines related to Treg and Th17 cells(IL-17,IL-21)
Time frame: up to 8 month of pregnancy
Elisa
Changes in exoression of cytokines gene.
Time frame: up to 8 month of pregnancy
RT pcr
2 secondary outcomes
Ongoing pregnancy rate in patients with Recurrent Pregnancy Loss (RPL)
Time frame: up to 8 month of pregnancy
Live berth rate in patients with Recurrent Pregnancy Loss (RPL).
Time frame: up to 1 year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Sep 2018.
- Results publication: PubMed 22889462Sugiura-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 publication: PubMed 19710204Santos 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 publication: PubMed 19819893King 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 publication: PubMed 24628478Goring 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 publication: PubMed 12765346Yamada 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 publication: PubMed 17166218Hutton 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 publication: PubMed 21095154Kolls 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mohammad Nouri, Ph.D study chair
Head of SCARM institute
Mehdi Yousefi, Immunologist study director
SCARM institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing IVIg in people with Recurrent Pregnancy Loss, run by Tabriz University of Medical Sciences at 1 site in Iran.
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 3 inclusion and 7 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: finished, as of the sponsor's last update on 17 Sep 2018. 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 Iran. 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 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in NK cells, T reg and Th17 cells frequency. (time frame: up to 8 month of pregnancy). The study lists 3 primary outcomes in all. 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 NCT03174951, which also lists 7 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 17 Sep 2018.