PregnancyCIPATNCT06925399
Changes in Natural Immunity in Pregnant Women With Autoimmune Thyroid Disease
An observational study of Pregnancy and Autoimmune Thyroid Disease, run by University of Rijeka at 1 site in Croatia.
Trial summary
Autoimmune thyroid disease (AITD) is the most common endocrine disorder in women of reproductive age, including during pregnancy. It encompasses two clinical conditions: autoimmune hyperthyroidism and hypothyroidism. Read more about this study
- Who is it for?
- Ages 18 to 45 years, women only
- Conditions the study is for
- Pregnancy, Autoimmune Thyroid Disease
- How many people
- 80 participants
- Where
- 1 siteCroatia
- Study dates
- 1 May 2025to 1 May 2027
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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 45 years
- Women only
- No healthy volunteers
- Adult
Study population: The planned prospective observational study will include pregnant women referred by primary care clinics in Rijeka and Primorsko-goranska County to the Clinical Department of Nuclear Medicine and the Department of Endocrinology, Diabetes and Metabolic Diseases of the Clinic of Internal Medicine of the Clinical Hospital Center Rijeka for thyroid examination and who have signed an informed consent form.
Who may be able to join
None listed.
Who cannot join
- pregnant women who refuse to give informed consent
- pregnant women under the age of 18
- pregnant women with malignant diseases
- pregnant women with thyrotoxicosis or hypothyroidism of a non-autoimmune nature and previous thyroidectomy or ablative therapy with iodine-131
- pregnant women with an acute or chronic disease that is not an autoimmune thyroid disease
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Croatia1 site
Faculty of Medicine University of Rijeka, Clinical Hospital Center Rijeka
Rijeka, Primorsko-goranska County, 51000
About this study
Official title: Dynamic Changes of Innate Immune Cells in Pregnant Women With Autoimmune Thyroid Disease
Autoimmune thyroid disease (AITD) is the most common endocrine disorder in women of reproductive age, including during pregnancy. It encompasses two clinical conditions: autoimmune hyperthyroidism and hypothyroidism. Pregnancy significantly affects thyroid function regulation, while thyroid dysfunction can influence fertility, pregnancy progression, and the postpartum health. Although the role of acquired immunity in AITD is well understood, recent research increasingly emphasizes innate immunity. Key cells involved in innate immunity include neutrophils, monocytes, and NKT cells. However, limited data exist on their role during pregnancy, especially in women with AITD.
This study aims to investigate the dynamic changes in neutrophils, monocytes and NKT cells during pregnancy and compare findings between women with normal pregnancies and those with AITD.
The study will analyze the frequency and activation status of these innate immune cells in peripheral blood samples collected during the first, second, and third trimesters. In addition, concentrations of thyrotropin, thyroid hormones, thyroglobulin, and thyroid autoantibodies, will be measured. A thyroid ultrasound will also be performed.
Read the detailed description
Autoimmune thyroid disease (AITD) affects approximately 2-17% of women of reproductive age, and represents the most common endocrine disorder in pregnancy. It includes autoimmune hyperthyroidism and hypothyroidism. Pregnancy has a significant impact on the regulation of thyroid function, and thyroid dysfunction may contribute to adverse pregnancy outcomes and neonatal complications.
Early detection of thyroid dysfunction during pregnancy is critical for optimal maternal-fetal health. While acquired immunity is a recognized contributor to the development of AITD, increasing attention has been given to the role of innate immunity. Innate immune mechanisms are essential for early immune response initiation and maintaining maternal tolerance toward the fetus, which represents a semi-allogeneic entity. This tolerogenic state is regulated both systemically and locally at the maternal-fetal interface.
The most relevant innate immune cells include neutrophils, monocytes/macrophages, and natural killer T (NKT) cells. Neutrophils participate in immune defense through cytotoxicity, phagocytosis, and cytokine secretion. Their numbers increase during pregnancy, and they play a role in implantation and placental development. Monocytes and decidual macrophages contribute to immune tolerance and placental remodeling. NKT cells, which bridge innate and adaptive immunity, perform immunoregulatory functions and have been observed in increased proportions in the decidua compared to peripheral blood. However, limited data are available regarding their role in pregnancy with thyroid autoimmunity.
The hypothesis of this study is that the numbers of neutrophils, monocytes and NKT cells and activation state of monocytes and NKT cells change during normal pregnancy and in pregnancy affected by AITD. The primary objective is to analyze differences in the frequency and activation marker expression of these immune cells between the two groups.
Peripheral blood mononuclear cells will be isolated, labeled, and analyzed using flow cytometry.
Expression of HLA-DR on monocytes and CD69 and CD25 on NKT cells will be quantified. In parallel, thyroid function parameters will be measured, including thyrotropin (TSH), free thyroxine (FT4), free triiodothyronine (FT3), thyroglobulin (Tg), and thyroid autoantibodies (TPOAb, TgAb, antiTSHR).
Pregnant women will be enrolled prospectively and will undergo blood sampling in each trimester. Ultrasound evaluation of the thyroid gland will be conducted to aid in diagnosis and classification. Participants will be categorized into groups based on thyroid hormone status and autoantibody titers: (1) normal pregnancy and (2) pregnancy with AITD.
The expected enrollment is 80 pregnant women (40 per group). All analyses will be conducted according to standardized laboratory and immunophenotyping protocols.
Statistical analysis will include group comparisons using t-tests or ANOVA for parametric data and Mann-Whitney or Kruskal-Wallis tests for non-parametric data. Correlation analyses will be conducted using Pearson or Spearman coefficients. A p-value < 0.05 will be considered statistically significant.
- Conditions
- Pregnancy, Autoimmune Thyroid Disease
- Keywords
- Pregnancy, Autoimmune thyroid disease, Innate immunity, NKT cells, Monocytes, Neutrophils
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Pregnant women referred for thyroid examination due to suspected thyroid disease | Adult pregnant women referred to the Clinical Department of Nuclear Medicine and the Department of Endocrinology, Diabetes and Metabolic Diseases of the Clinic of Internal Medicine of the Clinical Hospital Center Rijeka for thyroid examination due to suspected or known AITD and who have signed an informed consent form will participate in the study. The following data is collected and analyzed from pregnant women who are included in the examination on the basis of a signed consent form: Age, number of pregnancies, number of abortions, pregnancy outcome (abortion, premature birth, timely birth, delayed birth). The pregnant women included in the study will be tested three times, i.e. in the first, second and third trimester of pregnancy. Depending on the results of the hormone status and the thyroid autoantibody titre, the pregnant women will be divided into two groups: (1) normal pregnancy and (2) pregnant women with autoimmune thyroid disease. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Frequency of Neutrophils in Peripheral Blood
Frequency of neutrophils will be measured by differential blood count. Unit of Measure: Percent (%)
Measured: Within 24 months from enrollment; analysis over a 12-month period.
Frequency of Monocytes in Peripheral Blood
Monocyte frequency will be measured by flow cytometry and expressed as percentage of monocytes among CD45⁺ leukocytes.
Unit of Measure: Percent (%)
Measured: Within 24 months from enrollment; analysis over a 12-month period.
Frequency of NKT Cells in Peripheral Blood
NKT cell frequency will be measured by flow cytometry and expressed as percentage of NKT cells within CD3⁺ T lymphocytes.
Unit of Measure: Percent (%)
Measured: Within 24 months from enrollment; analysis over a 12-month period.
Secondary outcomes (10)
Expression of HLA-DR on Monocytes
HLA-DR expression on CD14⁺ monocytes will be measured using flow cytometry and expressed as percentage of HLA-DR⁺ monocytes.
Unit of Measure: Percent (%)
Measured: Within 24 months from enrollment.
Expression of CD25 on NKT Cells
CD25 expression on CD3⁺CD56⁺ NKT cells will be measured using flow cytometry and expressed as percentage of CD25⁺ cells.
Unit of Measure: Percent (%)
Measured: Within 24 months from enrollment.
Expression of CD69 on NKT Cells
CD69 expression on CD3⁺CD56⁺ NKT cells will be measured using flow cytometry and expressed as percentage of CD69⁺ cells.
Unit of Measure: Percent (%)
Measured: Time Frame: Within 24 months from enrollment.
Serum Concentration of TSH
TSH concentration will be measured using a chemiluminescent immunoassay (CLIA). Unit of Measure: mU/L
Measured: Measured at each trimester; analysis completed within 12 months of final collection.
Serum Concentration of Free T4
Unit of Measure: pmol/L
Measured: Measured at each trimester; analysis completed within 12 months.
Serum Concentration of Free T3
Unit of Measure: pmol/L
Measured: Measured at each trimester; analysis completed within 12 months.
Serum Concentration of Thyroglobulin (Tg)
Unit of Measure: ng/mL
Measured: Measured at each trimester; analysis completed within 12 months.
Serum Concentration of TPOAb
Unit of Measure: IU/mL
Measured: Measured at each trimester; analysis completed within 12 months.
Serum Concentration of TgAb
Unit of Measure: IU/mL
Measured: Measured at each trimester; analysis completed within 12 months.
Serum Concentration of antiTSHR
Unit of Measure: IU/L
Measured: Measured at each trimester; analysis completed within 12 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Apr 2025
- Study start1 May 2025 (estimated)
- Primary completion1 May 2026 (estimated)
- Study completion1 May 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for PregnancyStudies 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Rijeka
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Tatjana Bogović Crnčić, University of Rijeka
- Investigators
- Tatjana Bogović Crnčić, Principal investigator, Faculty of Medicine University of Rijeka
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06925399
- Sponsor's protocol ID
- uniri-iskusni-biomed-23-61
- Acronym
- CIPAT
- Status last verified
- Mar 2025
- First submitted
- 19 Mar 2025
- Last updated
- 13 Apr 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: All IPD that underlie results in a publication will be available upon request from Tatjana Bogović Crnčić
Study at a glance
From the registry record, last updated by the sponsor on 13 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dynamic Changes of Innate Immune Cells in Pregnant Women With Autoimmune Thyroid Disease
- ClinicalTrials.gov ID
- NCT06925399
- Acronym / sponsor ID
- CIPAT / uniri-iskusni-biomed-23-61
- Conditions
- Pregnancy, Autoimmune Thyroid Disease
- Keywords
- Pregnancy, Autoimmune thyroid disease, Innate immunity, NKT cells, Monocytes, Neutrophils
- Study type
- Observational
- Recruitment status
- Not yet recruiting
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- University of RijekaUniversity, hospital or other
- Study start
- 1 May 2025 (estimated)
- Primary completion
- 1 May 2026 (estimated)
- Study completion
- 1 May 2027 (estimated)
- First posted
- 13 Apr 2025 (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.
Autoimmune thyroid disease (AITD) is the most common endocrine disorder in women of reproductive age, including during pregnancy. It encompasses two clinical conditions: autoimmune hyperthyroidism and hypothyroidism. Pregnancy significantly affects thyroid function regulation, while thyroid dysfunction can influence fertility, pregnancy progression, and the postpartum health. Although the role of acquired immunity in AITD is well understood, recent research increasingly emphasizes innate immunity. Key cells involved in innate immunity include neutrophils, monocytes, and NKT cells. However, limited data exist on their role during pregnancy, especially in women with AITD.
This study aims to investigate the dynamic changes in neutrophils, monocytes and NKT cells during pregnancy and compare findings between women with normal pregnancies and those with AITD.
The study will analyze the frequency and activation status of these innate immune cells in peripheral blood samples collected during the first, second, and third trimesters. In addition, concentrations of thyrotropin, thyroid hormones, thyroglobulin, and thyroid autoantibodies, will be measured. A thyroid ultrasound will also be performed.
Detailed description
Autoimmune thyroid disease (AITD) affects approximately 2-17% of women of reproductive age, and represents the most common endocrine disorder in pregnancy. It includes autoimmune hyperthyroidism and hypothyroidism. Pregnancy has a significant impact on the regulation of thyroid function, and thyroid dysfunction may contribute to adverse pregnancy outcomes and neonatal complications.
Early detection of thyroid dysfunction during pregnancy is critical for optimal maternal-fetal health. While acquired immunity is a recognized contributor to the development of AITD, increasing attention has been given to the role of innate immunity. Innate immune mechanisms are essential for early immune response initiation and maintaining maternal tolerance toward the fetus, which represents a semi-allogeneic entity. This tolerogenic state is regulated both systemically and locally at the maternal-fetal interface.
The most relevant innate immune cells include neutrophils, monocytes/macrophages, and natural killer T (NKT) cells. Neutrophils participate in immune defense through cytotoxicity, phagocytosis, and cytokine secretion. Their numbers increase during pregnancy, and they play a role in implantation and placental development. Monocytes and decidual macrophages contribute to immune tolerance and placental remodeling. NKT cells, which bridge innate and adaptive immunity, perform immunoregulatory functions and have been observed in increased proportions in the decidua compared to peripheral blood. However, limited data are available regarding their role in pregnancy with thyroid autoimmunity.
The hypothesis of this study is that the numbers of neutrophils, monocytes and NKT cells and activation state of monocytes and NKT cells change during normal pregnancy and in pregnancy affected by AITD. The primary objective is to analyze differences in the frequency and activation marker expression of these immune cells between the two groups.
Peripheral blood mononuclear cells will be isolated, labeled, and analyzed using flow cytometry.
Expression of HLA-DR on monocytes and CD69 and CD25 on NKT cells will be quantified. In parallel, thyroid function parameters will be measured, including thyrotropin (TSH), free thyroxine (FT4), free triiodothyronine (FT3), thyroglobulin (Tg), and thyroid autoantibodies (TPOAb, TgAb, antiTSHR).
Pregnant women will be enrolled prospectively and will undergo blood sampling in each trimester. Ultrasound evaluation of the thyroid gland will be conducted to aid in diagnosis and classification. Participants will be categorized into groups based on thyroid hormone status and autoantibody titers: (1) normal pregnancy and (2) pregnancy with AITD.
The expected enrollment is 80 pregnant women (40 per group). All analyses will be conducted according to standardized laboratory and immunophenotyping protocols.
Statistical analysis will include group comparisons using t-tests or ANOVA for parametric data and Mann-Whitney or Kruskal-Wallis tests for non-parametric data. Correlation analyses will be conducted using Pearson or Spearman coefficients. A p-value < 0.05 will be considered statistically significant.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Pregnant women referred for thyroid examination due to suspected thyroid disease | – | –Adult pregnant women referred to the Clinical Department of Nuclear Medicine and the Department of Endocrinology, Diabetes and Metabolic Diseases of the Clinic of Internal Medicine of the Clinical Hospital Center Rijeka for thyroid examination due to suspected or known AITD and who have signed an informed consent form will participate in the study. The following data is collected and analyzed from pregnant women who are included in the examination on the basis of a signed consent form: Age, number of pregnancies, number of abortions, pregnancy outcome (abortion, premature birth, timely birth, delayed birth). The pregnant women included in the study will be tested three times, i.e. in the first, second and third trimester of pregnancy. Depending on the results of the hormone status and the thyroid autoantibody titre, the pregnant women will be divided into two groups: (1) normal pregnancy and (2) pregnant women with autoimmune thyroid disease. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
- Study population
- The planned prospective observational study will include pregnant women referred by primary care clinics in Rijeka and Primorsko-goranska County to the Clinical Department of Nuclear Medicine and the Department of Endocrinology, Diabetes and Metabolic Diseases of the Clinic of Internal Medicine of the Clinical Hospital Center Rijeka for thyroid examination and who have signed an informed consent form.
Key inclusion criteria (0 listed)
Key exclusion criteria (5 listed)
- pregnant women who refuse to give informed consent
- pregnant women under the age of 18
- pregnant women with malignant diseases
- pregnant women with thyrotoxicosis or hypothyroidism of a non-autoimmune nature and previous thyroidectomy or ablative therapy with iodine-131
- pregnant women with an acute or chronic disease that is not an autoimmune thyroid disease
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Frequency of Neutrophils in Peripheral Blood
Time frame: Within 24 months from enrollment; analysis over a 12-month period.
Frequency of neutrophils will be measured by differential blood count. Unit of Measure: Percent (%)
Frequency of Monocytes in Peripheral Blood
Time frame: Within 24 months from enrollment; analysis over a 12-month period.
Monocyte frequency will be measured by flow cytometry and expressed as percentage of monocytes among CD45⁺ leukocytes. Unit of Measure: Percent (%)
Frequency of NKT Cells in Peripheral Blood
Time frame: Within 24 months from enrollment; analysis over a 12-month period.
NKT cell frequency will be measured by flow cytometry and expressed as percentage of NKT cells within CD3⁺ T lymphocytes. Unit of Measure: Percent (%)
10 secondary outcomes
Expression of HLA-DR on Monocytes
Time frame: Within 24 months from enrollment.
Expression of CD25 on NKT Cells
Time frame: Within 24 months from enrollment.
Expression of CD69 on NKT Cells
Time frame: Time Frame: Within 24 months from enrollment.
Serum Concentration of TSH
Time frame: Measured at each trimester; analysis completed within 12 months of final collection.
Serum Concentration of Free T4
Time frame: Measured at each trimester; analysis completed within 12 months.
Serum Concentration of Free T3
Time frame: Measured at each trimester; analysis completed within 12 months.
Serum Concentration of Thyroglobulin (Tg)
Time frame: Measured at each trimester; analysis completed within 12 months.
Serum Concentration of TPOAb
Time frame: Measured at each trimester; analysis completed within 12 months.
Serum Concentration of TgAb
Time frame: Measured at each trimester; analysis completed within 12 months.
Serum Concentration of antiTSHR
Time frame: Measured at each trimester; analysis completed within 12 months.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Apr 2025.
- Individual participant dataSharing planned: Yes. All IPD that underlie results in a publication will be available upon request from Tatjana Bogović Crnčić
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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.
Tatjana Bogović Crnčić principal investigator
Faculty of Medicine University of Rijeka
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Pregnancy and Autoimmune Thyroid Disease, run by University of Rijeka at 1 site in Croatia.
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 0 inclusion and 5 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: opening soon, as of the sponsor's last update on 13 Apr 2025. 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 Croatia. 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.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Bogović Crnčić (0038551658365 ext. 0038551658370, tatjanabc@uniri.hr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Frequency of Neutrophils in Peripheral Blood (time frame: Within 24 months from enrollment; analysis over a 12-month period.). 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?
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 13 Apr 2025.