This study investigates the immunomodulatory effects of intradermal lymphocyte therapy in patients with RPL with immunological abnormalities such as imbalance of immune system cells including Treg and Th17, as well as other immunological parameters such as transcription factors related to these cells. Changes in the cytokine production and microRNAs involved in their function compared to before treatment will be examined in this study.
Design
200 patients with RPL with immunological disorders are randomly divided into two groups of 100, one group will receive intradermal lymphocyte therapy and other group will not receive intervention.
Settings and conduct
Tabriz Valiasr Hospital
Participants/Inclusion and exclusion criteria
After receiving informed consent from people with RPL and also a control group consisting of healthy and fertile women with a history of successful previous pregnancies, heparinized blood is taken and mononuclear blood cells are isolated. Flow cytometry technique will then be used to count the number of T reg, Th-17, NK and B cells. The results of flow cytometry studies will be compared, and 200 patients with RPL with immunological disorders and 100 people as a healthy control group will be included in this study. The group of 200 patients with RPL was randomly divided into two groups of 100, one group receiving lymphocyte therapy and the other group not receiving treatment.
Intervention groups
According to the standard protocol, 2 × 107 of the husband's lymphocytes will be injected subcutaneously on the forearm or arms of patients with recurrent miscarriages. The number of injections is three times and at intervals of one month.
Main outcome variables
Immunological parameters such as Treg and Th17 cell frequency, gene and protein expression of Foxp3 and RORyt, gene expression of cytokines and the expression of microRNAs, including mir-146a, mir-155 and mir-326.
General information
Reason for update
Acronym
RPL
IRCT registration information
IRCT registration number:IRCT20160422027520N19
Registration date:2021-10-12, 1400/07/20
Registration timing:prospective
Last update:2021-10-12, 1400/07/20
Update count:0
Registration date
2021-10-12, 1400/07/20
Registrant information
Name
Mehdi Yousefi
Name of organization / entity
Department of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
Country
Iran (Islamic Republic of)
Phone
+98 41 3336 4665
Email address
yousefime@tbzmed.ac.ir
Recruitment status
Recruitment complete
Funding source
Expected recruitment start date
2021-10-22, 1400/07/30
Expected recruitment end date
2022-05-20, 1401/02/30
Actual recruitment start date
empty
Actual recruitment end date
empty
Trial completion date
empty
Scientific title
Intradermal lymphocyte therapy in recurrent pregnancy loss patients with immunologic abnormalities
Public title
Intradermal injection of lymphocytes in recurrent pregnancy loss patients
Purpose
Treatment
Inclusion/Exclusion criteria
Inclusion criteria:
Having at least three consecutive abortions
Having regular menstrual cycles
BMI of people below 30
Have no uterine pathology
Our patients will be selected only from Azerbaijan.
Patients were selected whose semen analysis and DNA fragmentation test were normal.
Exclusion criteria:
Patients under the age of 18 and over 40 years
Patients who themselves or their spouse have abnormal karyotypes or genetic or chromosomal abnormalities.
Patients with chronic underlying disease who have to take certain medications.
Patients with intrauterine anomalies.
Having polycystic ovary syndrome
Patients who test positive for HIV, HCV or HBV
Age
From 18 years old to 40 years old
Gender
Both
Phase
1-2
Groups that have been masked
Participant
Data analyser
Sample size
Target sample size:
200
Randomization (investigator's opinion)
Randomized
Randomization description
At first, the sample size of 200 patients with RPL that met our inclusion criteria was considered as the total sample size. 'Random allocation rule' method was used for randomization, where numbers were randomly assigned to cards on a random order of one to 200. Even numbers were assigned to the treatment group and odd numbers to the placebo group. In this method, the balance will be reached at the end of the study in the number of people assigned to each group. Each card was placed in sealed and opaqued envelopes to hide the random assignment.
Blinding (investigator's opinion)
Double blinded
Blinding description
The participants and the person who analyzed the results were blinded in this study. Participants were aware of the study before being randomized and informed consent was obtained from them. It should be noted that the person analyzing the results had no other role in this study.
Placebo
Used
Assignment
Parallel
Other design features
Secondary Ids
empty
Ethics committees
1
Ethics committee
Name of ethics committee
Ethics committee of Tabriz University of Medical Sciences
Street address
Tabriz University of Medical Sciences , Daneshghah st, Tabriz
City
Tabriz
Province
East Azarbaijan
Postal code
5166614766
Approval date
2021-10-06, 1400/07/14
Ethics committee reference number
IR-TBZMED.REC.1400.597
Health conditions studied
1
Description of health condition studied
Recurrent Pregnancy Loss(RPL)
ICD-10 code
ICD-10 code description
Primary outcomes
1
Description
Frequency of Treg and Th17 cells
Timepoint
Before and after the intervention
Method of measurement
Flow cytometry
2
Description
Gene expression levels of Foxp3 and RORyt
Timepoint
Before and after the intervention
Method of measurement
Real-time PCR
3
Description
Protein expression levels of Foxp3 and RORyt
Timepoint
Before and after the intervention
Method of measurement
Western blot
4
Description
Gene expression levels of IL-10, IL-17, IL-21, IL-23, TGF-β
Timepoint
Before and after the intervention
Method of measurement
Real-time PCR
5
Description
Secretion levels of IL-10, IL-17, IL-21, IL-23, TGF-β
Timepoint
Before and after the intervention
Method of measurement
ELISA
6
Description
Gene expression levels of mir-146a و mir-155 و mir-326
Timepoint
Before and after the intervention
Method of measurement
real-time PCR
Secondary outcomes
empty
Intervention groups
1
Description
Intervention group: The group of 200 patients with recurrent miscarriage was randomly divided into two groups of 100, one group receiving lymphocyte therapy and the other group not receiving treatment. Is injected. According to the standard protocol, 2 × 107 of husband's lymphocytes are injected subcutaneously into patients with recurrent miscarriages. The number of injections is three times and at intervals of one month.
Category
Treatment - Other
Recruitment centers
1
Recruitment center
Name of recruitment center
Infertility center at Valiasr Hospital
Full name of responsible person
Dr. Mehdi Yousefi
Street address
Infertility center at Valiasr Hospital, Aflak-nama Sq, Zaferaniyeh Ave, Tabriz
City
Tabriz
Province
East Azarbaijan
Postal code
5166614766
Phone
+98 41 3327 3000
Email
mehdi_yusefi@yahoo.com
Sponsors / Funding sources
1
Sponsor
Name of organization / entity
Tabriz University of Medical Sciences
Full name of responsible person
Mehdi Yousefi
Street address
Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz
City
Tabriz
Province
East Azarbaijan
Postal code
5166614766
Phone
+98 41 3334 9525
Email
mehdi_yusefi@yahoo.com
Web page address
Grant name
Grant code / Reference number
Is the source of funding the same sponsor organization/entity?
Yes
Title of funding source
Tabriz University of Medical Sciences
Proportion provided by this source
100
Public or private sector
Public
Domestic or foreign origin
Domestic
Category of foreign source of funding
empty
Country of origin
Type of organization providing the funding
Academic
Person responsible for general inquiries
Contact
Name of organization / entity
Tabriz University of Medical Sciences
Full name of responsible person
Mehdi Yousefi
Position
PhD in Medical Immunology
Latest degree
Ph.D.
Other areas of specialty/work
Immunology
Street address
Tabriz University of Medical Sciences , Daneshghah st, Tabriz,
City
Tabriz
Province
East Azarbaijan
Postal code
5166614766
Phone
+98 41 3336 4665
Email
mehdi_yusefi@yahoo.com
Person responsible for scientific inquiries
Contact
Name of organization / entity
Tabriz University of Medical Sciences
Full name of responsible person
Mehdi Yousefi
Position
PhD in Immunology- Associate professor
Latest degree
Ph.D.
Other areas of specialty/work
Immunology
Street address
Tabriz University of Medical Sciences , Daneshghah st, Tabriz,
City
Tabriz
Province
East Azarbaijan
Postal code
5166614766
Phone
+98 41 3336 4665
Email
mehdi_yusefi@yahoo.com
Person responsible for updating data
Contact
Name of organization / entity
Tabriz University of Medical Sciences
Full name of responsible person
Sanam Dolati
Position
Assistant Professor of Immunology
Latest degree
Ph.D.
Other areas of specialty/work
Immunology
Street address
Department of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
City
Tabriz
Province
East Azarbaijan
Postal code
5166614766
Phone
00
Email
sanam.dolati@gmail.com
Sharing plan
Deidentified Individual Participant Data Set (IPD)
Undecided - It is not yet known if there will be a plan to make this available
Study Protocol
Undecided - It is not yet known if there will be a plan to make this available
Statistical Analysis Plan
Undecided - It is not yet known if there will be a plan to make this available
Informed Consent Form
Undecided - It is not yet known if there will be a plan to make this available
Clinical Study Report
Undecided - It is not yet known if there will be a plan to make this available
Analytic Code
Undecided - It is not yet known if there will be a plan to make this available
Data Dictionary
Undecided - It is not yet known if there will be a plan to make this available