Unexplained Recurrent Miscarriage and Recurrent Implantation FailurePhase 1/2immunotherapyNCT03081325
A Preliminary Study About Unexplained Recurrent Miscarriage and Repeated Implantation Failure Patients Treated With Low-dose Lymphocyte Immunotherapy
A Phase 1/2 study testing low-dose lymphocyte immunotherapy in people with Unexplained Recurrent Miscarriage and Recurrent Implantation Failure, run by Nanjing University at 1 site in China.
Trial summary
Recurrent miscarriage(RM) and recurrent implantation failure (RIF) are clinical challenge for clinicians and patients who are desperate for a healthy child.The specific etiology contains chromosomal abnormalities, reproductive anatomical abnormalities, endocrine disorders, reproductive system infections, autoimmune… Read more about this study
- Who is it for?
- Ages 20 to 40 years, women only
- Conditions the study is for
- Unexplained Recurrent Miscarriage and Recurrent Implantation Failure
- What is being tested?
- low-dose lymphocyte immunotherapy
- Type of treatment
- Vaccines, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 292 participants
- Where
- 1 siteChina
- Study dates
- Mar 2015to 20 Jul 2017
- Phase
- Phase 1/2
- 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 20 to 40 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- Healthy except for their history of recurrent abortions and were negative for blocking antibodies
- Willing to receive follow up
Who cannot join
- Patients with genetic impairment
- Patients with Mullerian anomaly
- Patients with hormonal deficiency
- Patients with metabolic disorder
- Patients with infectious disease
- Patients with autoimmune abnormalities
Trial locations and contacts
1 site in 1 country.
China1 site
Reproductive Medicine Center, The Affiliated Drum Tower Hospital of Nanjing University Medical School
Nanjing, Jiangsu, 210008
About this study
Recurrent miscarriage(RM) and recurrent implantation failure (RIF) are clinical challenge for clinicians and patients who are desperate for a healthy child.The specific etiology contains chromosomal abnormalities, reproductive anatomical abnormalities, endocrine disorders, reproductive system infections, autoimmune and environmental factors. However there are still 50% to 60% RM and RIF which don't have a clear cause,mainly associated with alloimmune factors.Among various treatments,lymphocytes active immunotherapy is the most common treatment method, and its clinical efficacy is widely recognized although its action mechanism is not clear so far.
Read the detailed description
The main mechanism of active immunotherapy includes upregulating Th2-type cytokines, downregulating Th1-type cytokines, making Th1 / Th2 shift to Th2, inducing maternal serum IL-6 and sIL6R, PIBF, EGF; inducing the expression of Fas / Fasl on lymphocyte surface; increasing the proportion of CD8 + cells, Th2-type cells and CD + CD25 + Treg cells, decreasing the activity of CD56 + CD16 + NK cell and so on.The purpose of this study is to observe the treatment effects of active immunotherapy on uRM and RIF patients. What's more,we will used flow cytometry, and quantitative real-time PCR (qPCR) methods to characterize Th1、Th2 and Treg cell populations after immunotherapy,ecpecting to find out the exact molecule mechanism of immunotherapy with paternal or third party lymphocytes.
- Being tested
- low-dose lymphocyte immunotherapy
- Keywords
- uRM, RIF, Th1, Th2, Treg, lymphocyte immunotherapy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
low-dose lymphocyte immunotherapyProcedure or surgery
Peripheral venous blood (PBMCs) was drawn from the husbands of uRM and RIF patients and then the PBMCs were resuspended and administered intradermally to uRM and RIF patients 3 times at 3-week intervals. Once conceived, the uRM and RIF patients undergo 2 rounds of treatment at 8-week intervals.
| Study group | Role | What they receive |
|---|---|---|
| lymphocyte immunotherapy on uRM and RIF | Experimental | Donor (husband or third party) lymphocytes were prepared by Ficoll-Paque centrifugation; the cells were washed with sterile saline and resuspended in 1 ml at a concentration of 20-40 × 106 cells/ml. The cells were given to the female partner by 4-6 intradermal injected. In this study, the lymphocyte immunization therapies were performed every 3 weeks for 3 times. After that we test Th1/Th2/Treg, if they become normal, the patients can prepare for pregnancy. Receives: Procedure: low-dose lymphocyte immunotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
T cell proportion
We use flow cytometry to detecte peripheral blood Th1、Th2 and Treg cells of uRM and RIF patients before and after low-dose lymphocyte immunotherapy to see if the immunotherapy have treatment effect on Th1/Th2/Treg paradigm disorder
Measured: 1 year
Abortion rate
We undergo follow-up of all the uRM patients to see the abortion rate (miscarriage was confirmed by ultrasound before the 20th week of gestation) after lymphocyte immunotherapy
Measured: 1 year
IVF outcomes
We observed the the implantation rate, clinical pregnancy rate, and ongoing pregnancy rate of RIF patients after low-dose lymphocyte immunotherapy
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Mar 2017
- Study startMar 2015
- Primary completionJun 2017
- Study completion20 Jul 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Unexplained Recurrent Miscarriage and Recurrent Implantation FailureStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 292 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nanjing University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Li-jun Ding, Nanjing University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03081325
- Sponsor's protocol ID
- BL2015007
- Acronym
- immunotherapy
- Status last verified
- Apr 2018
- First submitted
- 8 Mar 2017
- Last updated
- 11 Apr 2018
- Results posted
- No
Publications
Liu M, Zhen X, Song H, Chen J, Sun X, Li X, Zhou J, Yan G, Ding L, Sun H. Low-dose lymphocyte immunotherapy rebalances the peripheral blood Th1/Th2/Treg paradigm in patients with unexplained recurrent miscarriage. Reprod Biol Endocrinol. 2017 Dec 16;15(1):95. doi: 10.1186/s12958-017-0315-9.
PubMed 29246150
Study at a glance
From the registry record, last updated by the sponsor on 11 Apr 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Preliminary Study About Unexplained Recurrent Miscarriage and Repeated Implantation Failure Patients Treated With Low-dose Lymphocyte Immunotherapy
- ClinicalTrials.gov ID
- NCT03081325
- Acronym / sponsor ID
- immunotherapy / BL2015007
- Keywords
- uRM, RIF, Th1, Th2, Treg, lymphocyte immunotherapy
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 292 participants (actual)
- Lead sponsor
- Nanjing UniversityUniversity, hospital or other
- Study start
- Mar 2015
- Primary completion
- Jun 2017 (actual)
- Study completion
- 20 Jul 2017 (actual)
- First posted
- 16 Mar 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.
Recurrent miscarriage(RM) and recurrent implantation failure (RIF) are clinical challenge for clinicians and patients who are desperate for a healthy child.The specific etiology contains chromosomal abnormalities, reproductive anatomical abnormalities, endocrine disorders, reproductive system infections, autoimmune and environmental factors. However there are still 50% to 60% RM and RIF which don't have a clear cause,mainly associated with alloimmune factors.Among various treatments,lymphocytes active immunotherapy is the most common treatment method, and its clinical efficacy is widely recognized although its action mechanism is not clear so far.
Detailed description
The main mechanism of active immunotherapy includes upregulating Th2-type cytokines, downregulating Th1-type cytokines, making Th1 / Th2 shift to Th2, inducing maternal serum IL-6 and sIL6R, PIBF, EGF; inducing the expression of Fas / Fasl on lymphocyte surface; increasing the proportion of CD8 + cells, Th2-type cells and CD + CD25 + Treg cells, decreasing the activity of CD56 + CD16 + NK cell and so on.The purpose of this study is to observe the treatment effects of active immunotherapy on uRM and RIF patients. What's more,we will used flow cytometry, and quantitative real-time PCR (qPCR) methods to characterize Th1、Th2 and Treg cell populations after immunotherapy,ecpecting to find out the exact molecule mechanism of immunotherapy with paternal or third party lymphocytes.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| lymphocyte immunotherapy on uRM and RIF | Experimental | Procedure: low-dose lymphocyte immunotherapyDonor (husband or third party) lymphocytes were prepared by Ficoll-Paque centrifugation; the cells were washed with sterile saline and resuspended in 1 ml at a concentration of 20-40 × 106 cells/ml. The cells were given to the female partner by 4-6 intradermal injected. In this study, the lymphocyte immunization therapies were performed every 3 weeks for 3 times. After that we test Th1/Th2/Treg, if they become normal, the patients can prepare for pregnancy. |
Who may qualify
- Ages
- 20 to 40 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- Healthy except for their history of recurrent abortions and were negative for blocking antibodies
- Willing to receive follow up
Key exclusion criteria (6 listed)
- Patients with genetic impairment
- Patients with Mullerian anomaly
- Patients with hormonal deficiency
- Patients with metabolic disorder
- Patients with infectious disease
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 |
|---|---|---|
| low-dose lymphocyte immunotherapyPeripheral venous blood (PBMCs) was drawn from the husbands of uRM and RIF patients and then the PBMCs were resuspended and administered intradermally to uRM and RIF patients 3 times at 3-week intervals. Once conceived, the uRM and RIF patients undergo 2 rounds of treatment at 8-week intervals. | Procedure or surgery | lymphocyte immunotherapy on uRM and RIF |
Primary outcome
T cell proportion
Time frame: 1 year
We use flow cytometry to detecte peripheral blood Th1、Th2 and Treg cells of uRM and RIF patients before and after low-dose lymphocyte immunotherapy to see if the immunotherapy have treatment effect on Th1/Th2/Treg paradigm disorder
Abortion rate
Time frame: 1 year
We undergo follow-up of all the uRM patients to see the abortion rate (miscarriage was confirmed by ultrasound before the 20th week of gestation) after lymphocyte immunotherapy
IVF outcomes
Time frame: 1 year
We observed the the implantation rate, clinical pregnancy rate, and ongoing pregnancy rate of RIF patients after low-dose lymphocyte immunotherapy
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 11 Apr 2018.
- Derived from this study: PubMed 29246150Liu M, Zhen X, Song H, Chen J, Sun X, Li X, Zhou J, Yan G, Ding L, Sun H. Low-dose lymphocyte immunotherapy rebalances the peripheral blood Th1/Th2/Treg paradigm in patients with unexplained recurrent miscarriage. Reprod Biol Endocrinol. 2017 Dec 16;15(1):95. doi: 10.1186/s12958-017-0315-9.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing low-dose lymphocyte immunotherapy in people with Unexplained Recurrent Miscarriage and Recurrent Implantation Failure, run by Nanjing 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 2 inclusion and 6 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 11 Apr 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 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
T cell proportion (time frame: 1 year). 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 NCT03081325, which also lists 1 linked publication.
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 11 Apr 2018.