AspirinNCT06882850
Immunomodulation During Pregnancy
An observational study of Aspirin and Pregnancy Complications, run by Unidade Local de Saúde de Coimbra, EPE at 1 site in Portugal.
Trial summary
The goal of this observational study is to learn about the effects of low dose aspirin in immunity Pregnant women taking aspirin for other reasons (preeclampsia prevention) will be studied. Read more about this study
- Who is it for?
- Ages 18 years and older, women onlyHealthy volunteers can take part
- Conditions the study is for
- Aspirin, Pregnancy Complications, Immunology
- How many people
- 30 participants
- Where
- 1 sitePortugal
- Study dates
- 1 Feb 2024to 31 Mar 2025
- How long will I take part?
- 30 Weeks
- 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 years and older
- Women only
- Healthy volunteers accepted
- Adult, Older adult
Study population: Women attending routine low-risk prenatal consultations at the Department of Obstetrics of the Centro Hospitalar Universitário de Coimbra (CHUC). A written procedure detailing the research and the general objectives of the proposal will be submitted to the hospital's ethics committee for approval. Informed consent from patients will be obtained under strict ethical protocols.
Who may be able to join
- Patients attending prenatal consultations at the Obstetrics Service A of CHUC, with the first consultation occurring before 14 weeks of gestation
- Gestational age determined by first-trimester ultrasound
- Study group: Women classified as high risk for PE according to clinical/historical criteria and the Fetal Medicine Foundation algorithm. LDA-naïve.
Who cannot join
- Autoimmune diseases
- Prior use of LDA or other immunomodulatory medication before potential recruitment
- History of spontaneous miscarriages and/or medical termination of pregnancy
- Fetal malformation
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
João Sargento-Freitas, PhD contact
Portugal1 site, 1 recruiting
- Recruiting
Unidade Local de Saúde de Coimbra, E.P.E.
Coimbra, Coimbra District, 3000-075
Ana Areia, PhD, MD, +351917212222, analuisareia@gmail.com
About this study
Official title: Immunomodulation During Pregnancy Through Low-Dose Aspirin: a Hypothetical Mechanism for the Prevention of Preeclampsia?
The goal of this observational study is to learn about the effects of low dose aspirin in immunity Pregnant women taking aspirin for other reasons (preeclampsia prevention) will be studied. The main question it aims to answer is: evaluate the effect of LDA on the modulation of innate immunity cells (NK cells, monocytes, γδ T cells) and/or acquired immunity (B and T lymphocytes, Treg cells, Th cells).
Participants already taking intervention A as part of their regular medical care for RA will answer online survey questions about their joint pain for 5 years.
Read the detailed description
The main objective of this study is to evaluate the effect of LDA on the modulation of innate immunity cells (NK cells, monocytes, γδ T cells) and/or acquired immunity (B and T lymphocytes, Treg cells, Th cells). The secondary objectives are to quantify pro-inflammatory and anti-inflammatory cytokines before and after LDA administration, as well as to assess maternal and fetal outcomes, comparing these parameters with those of low-risk PE pregnancies that do not require prophylactic LDA administration.
A prospective longitudinal study will be conducted, lasting a minimum of 40 weeks and a maximum of 24 months. Singleton pregnancies monitored at the Centro Hospitalar e Universitário de Coimbra will be included, with the first consultation occurring before 14 weeks of gestation and gestational age determined by first-trimester ultrasound. The study group will consist of women at high risk of PE according to clinical/historical criteria, who have not yet started LDA intake at the time of recruitment. Pregnant women will be classified as having a low or high risk of PE (risk of ≥ 1 in 50 for preterm PE) using the Fetal Medicine Foundation algorithm. This algorithm evaluates maternal clinical risk factors, mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), and pregnancy-associated plasma protein A (PAPP-A). Women classified as high-risk will receive prophylactic aspirin (150 mg once daily).
As this is a preliminary study, 30 pregnant women will initially be included: 15 at high risk of PE (study group) and 15 at low risk (control group). Peripheral blood samples will be collected from both groups, utilizing routine pregnancy blood draws, at three time points (1st, 2nd, and 3rd trimesters). This will allow the evaluation of fluctuations in immune cells (NK cells, B and T lymphocytes, Treg cells, Th cells) and cytokine levels (IL-1, IL-6, IL-8, TNF-α, INF-γ, TGF-β, and IL-10). In high-risk PE pregnancies, additional peripheral blood samples will be collected before LDA administration and four weeks afterward.
Flow cytometry methodology will be used to determine immune cell frequencies, while plasma cytokine levels will be measured using ELISA and Luminex methodologies. After delivery, in both groups, histopathological evaluation (immunohistochemical staining) of the placenta will be performed, analyzing the aforementioned immune cells, as well as umbilical cord blood analysis using flow cytometry.
- Conditions
- Aspirin, Pregnancy Complications, Immunology
- Keywords
- Immunology, Pregnancy, Aspirin, Lymphocytes, T-Lymphocytes
- Medical subject headings
- Pregnancy Complications
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 |
|---|---|---|
| Healthy pregnancies | High-risk preeclampsia pregnencies |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evaluate the effect of Low dose aspirin (LDA) on the modulation of immunity cells
innate immunity cells and/or acquired immunity
Measured: 30 weeks
Th1, Th2, Treg, Th17, and Th1/17
Absolute and relative frequencies in total lymphocytes (LY, x10⁹/L; %)
Measured: 30 weeks
Secondary outcomes (3)
Maternal outcomes
Maternal Complications: Gestational diabetes, gestational hypertension, preterm birth
Measured: 30 weeks
Maternal outcomes
Weeks of Delivery
Measured: 30 weeks
Maternal outcomes
Type of delivery (vaginal or cesarean section)
Measured: 30 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Mar 2025
- Study start1 Feb 2024
- Primary completion30 Mar 2025 (estimated)
- Study completion31 Mar 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for AspirinStudies 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
- 30 participants (estimated)
- Target duration
- 30 Weeks
Sponsor and investigators
- Lead sponsor
- Unidade Local de Saúde de Coimbra, EPE
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ana Luisa Areia, Unidade Local de Saúde de Coimbra, EPE
- Investigators
- Ana L Areia, PhD MD, Principal investigator, University of Coimbra
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06882850
- Sponsor's protocol ID
- OBS.SF.160/2022
- Status last verified
- Feb 2025
- First submitted
- 10 Mar 2025
- Last updated
- 19 Mar 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: All of my research in the form of an article with the whole protocol and results
Publications
1. Cadavid AP. Aspirin: The Mechanism of Action Revisited in the Context of Pregnancy Complications. Front Immunol. 2017;8:261. 2. Mittelberger J, Seefried M, Franitza M, Garrido F, Ditsch N, Jeschke U, et al. The Role of the Immune Checkpoint Molecules PD-1/PD-L1 and TIM-3/Gal-9 in the Pathogenesis of Preeclampsia-A Narrative Review. Medicina (Kaunas). 2022;58(2). 3. Khanabdali R, Shakouri-Motlagh A, Wilkinson S, Murthi P, Georgiou HM, Brennecke SP, et al. Low-dose aspirin treatment enhances the adhesion of preeclamptic decidual mesenchymal stem/stromal cells and reduces their production of pro-inflammatory cytokines. J Mol Med (Berl). 2018;96(11):1215-1225. 4. Panagodage S, Yong HE, Da Silva Costa F, Borg AJ, Kalionis B, Brennecke SP, et al. Low-Dose Acetylsalicylic Acid Treatment Modulates the Production of Cytokines and Improves Trophoblast Function in an in Vitro Model of Early-Onset Preeclampsia. Am J Pathol. 2016;186(12):3217-3224. 5. Robillard PY, Dekker G, Scioscia M, Saito S. Progress in the understanding of the pathophysiology of immunologic maladaptation related to early-onset preeclampsia and metabolic syndrome related to late-onset preeclampsia. Am J Obstet Gynecol. 2022;226(2S):S867-S875. 6. Brox R, Hackstein H. Physiologically relevant aspirin concentrations trigger immunostimulatory cytokine production by human leukocytes. PLoS One. 2021;16(8):e0254606. 7. Dong W, Yin L. Expression of lipoxin A4, TNFalpha and IL-1beta in maternal peripheral blood, umbilical cord blood and placenta, and their significance in pre-eclampsia. Hypertens Pregnancy. 2014;33(4):449-456. 8. Tung YT, Wei CH, Yen CC, Lee PY, Ware LB, Huang HE, et al. Aspirin Attenuates Hyperoxia-Induced Acute Respiratory Distress Syndrome (ARDS) by Suppressing Pulmonary Inflammation via the NF-kappaB Signaling Pathway. Front Pharmacol. 2021;12:793107. 9. Dong W, Liu X, Liu W, Wang C, Zhao S, Wen S, et al. Dual antiplatelet therapy improves functional recovery and inhibits inflammation after ce
Areia AL, Almeida J, Alves V, Mota-Pinto A, Sa H. Modulation of Immune Cells by Aspirin During Pregnancy. Immunology. 2026 Feb;177(2):329-338. doi: 10.1111/imm.70051. Epub 2025 Oct 14.
PubMed 41087834
Study at a glance
From the registry record, last updated by the sponsor on 19 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Immunomodulation During Pregnancy Through Low-Dose Aspirin: a Hypothetical Mechanism for the Prevention of Preeclampsia?
- ClinicalTrials.gov ID
- NCT06882850
- Acronym / sponsor ID
- OBS.SF.160/2022
- Conditions
- Aspirin, Pregnancy Complications, Immunology
- Keywords
- Immunology, Pregnancy, Aspirin, Lymphocytes, T-Lymphocytes
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Unidade Local de Saúde de Coimbra, EPEUniversity, hospital or other
- Study start
- 1 Feb 2024 (actual)
- Primary completion
- 30 Mar 2025 (estimated)
- Study completion
- 31 Mar 2025 (estimated)
- First posted
- 19 Mar 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.
The goal of this observational study is to learn about the effects of low dose aspirin in immunity Pregnant women taking aspirin for other reasons (preeclampsia prevention) will be studied. The main question it aims to answer is: evaluate the effect of LDA on the modulation of innate immunity cells (NK cells, monocytes, γδ T cells) and/or acquired immunity (B and T lymphocytes, Treg cells, Th cells).
Participants already taking intervention A as part of their regular medical care for RA will answer online survey questions about their joint pain for 5 years.
Detailed description
The main objective of this study is to evaluate the effect of LDA on the modulation of innate immunity cells (NK cells, monocytes, γδ T cells) and/or acquired immunity (B and T lymphocytes, Treg cells, Th cells). The secondary objectives are to quantify pro-inflammatory and anti-inflammatory cytokines before and after LDA administration, as well as to assess maternal and fetal outcomes, comparing these parameters with those of low-risk PE pregnancies that do not require prophylactic LDA administration.
A prospective longitudinal study will be conducted, lasting a minimum of 40 weeks and a maximum of 24 months. Singleton pregnancies monitored at the Centro Hospitalar e Universitário de Coimbra will be included, with the first consultation occurring before 14 weeks of gestation and gestational age determined by first-trimester ultrasound. The study group will consist of women at high risk of PE according to clinical/historical criteria, who have not yet started LDA intake at the time of recruitment. Pregnant women will be classified as having a low or high risk of PE (risk of ≥ 1 in 50 for preterm PE) using the Fetal Medicine Foundation algorithm. This algorithm evaluates maternal clinical risk factors, mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), and pregnancy-associated plasma protein A (PAPP-A). Women classified as high-risk will receive prophylactic aspirin (150 mg once daily).
As this is a preliminary study, 30 pregnant women will initially be included: 15 at high risk of PE (study group) and 15 at low risk (control group). Peripheral blood samples will be collected from both groups, utilizing routine pregnancy blood draws, at three time points (1st, 2nd, and 3rd trimesters). This will allow the evaluation of fluctuations in immune cells (NK cells, B and T lymphocytes, Treg cells, Th cells) and cytokine levels (IL-1, IL-6, IL-8, TNF-α, INF-γ, TGF-β, and IL-10). In high-risk PE pregnancies, additional peripheral blood samples will be collected before LDA administration and four weeks afterward.
Flow cytometry methodology will be used to determine immune cell frequencies, while plasma cytokine levels will be measured using ELISA and Luminex methodologies. After delivery, in both groups, histopathological evaluation (immunohistochemical staining) of the placenta will be performed, analyzing the aforementioned immune cells, as well as umbilical cord blood analysis using flow cytometry.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 30 Weeks
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Healthy pregnancies | – | –High-risk preeclampsia pregnencies |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Women attending routine low-risk prenatal consultations at the Department of Obstetrics of the Centro Hospitalar Universitário de Coimbra (CHUC). A written procedure detailing the research and the general objectives of the proposal will be submitted to the hospital's ethics committee for approval. Informed consent from patients will be obtained under strict ethical protocols.
Key inclusion criteria (3 listed)
- Patients attending prenatal consultations at the Obstetrics Service A of CHUC, with the first consultation occurring before 14 weeks of gestation
- Gestational age determined by first-trimester ultrasound
- Study group: Women classified as high risk for PE according to clinical/historical criteria and the Fetal Medicine Foundation algorithm. LDA-naïve.
Key exclusion criteria (4 listed)
- Autoimmune diseases
- Prior use of LDA or other immunomodulatory medication before potential recruitment
- History of spontaneous miscarriages and/or medical termination of pregnancy
- Fetal malformation
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
Evaluate the effect of Low dose aspirin (LDA) on the modulation of immunity cells
Time frame: 30 weeks
innate immunity cells and/or acquired immunity
Th1, Th2, Treg, Th17, and Th1/17
Time frame: 30 weeks
Absolute and relative frequencies in total lymphocytes (LY, x10⁹/L; %)
3 secondary outcomes
Maternal outcomes
Time frame: 30 weeks
Maternal outcomes
Time frame: 30 weeks
Maternal outcomes
Time frame: 30 weeks
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 19 Mar 2025.
- Background1. Cadavid AP. Aspirin: The Mechanism of Action Revisited in the Context of Pregnancy Complications. Front Immunol. 2017;8:261. 2. Mittelberger J, Seefried M, Franitza M, Garrido F, Ditsch N, Jeschke U, et al. The Role of the Immune Checkpoint Molecules PD-1/PD-L1 and TIM-3/Gal-9 in the Pathogenesis of Preeclampsia-A Narrative Review. Medicina (Kaunas). 2022;58(2). 3. Khanabdali R, Shakouri-Motlagh A, Wilkinson S, Murthi P, Georgiou HM, Brennecke SP, et al. Low-dose aspirin treatment enhances the adhesion of preeclamptic decidual mesenchymal stem/stromal cells and reduces their production of pro-inflammatory cytokines. J Mol Med (Berl). 2018;96(11):1215-1225. 4. Panagodage S, Yong HE, Da Silva Costa F, Borg AJ, Kalionis B, Brennecke SP, et al. Low-Dose Acetylsalicylic Acid Treatment Modulates the Production of Cytokines and Improves Trophoblast Function in an in Vitro Model of Early-Onset Preeclampsia. Am J Pathol. 2016;186(12):3217-3224. 5. Robillard PY, Dekker G, Scioscia M, Saito S. Progress in the understanding of the pathophysiology of immunologic maladaptation related to early-onset preeclampsia and metabolic syndrome related to late-onset preeclampsia. Am J Obstet Gynecol. 2022;226(2S):S867-S875. 6. Brox R, Hackstein H. Physiologically relevant aspirin concentrations trigger immunostimulatory cytokine production by human leukocytes. PLoS One. 2021;16(8):e0254606. 7. Dong W, Yin L. Expression of lipoxin A4, TNFalpha and IL-1beta in maternal peripheral blood, umbilical cord blood and placenta, and their significance in pre-eclampsia. Hypertens Pregnancy. 2014;33(4):449-456. 8. Tung YT, Wei CH, Yen CC, Lee PY, Ware LB, Huang HE, et al. Aspirin Attenuates Hyperoxia-Induced Acute Respiratory Distress Syndrome (ARDS) by Suppressing Pulmonary Inflammation via the NF-kappaB Signaling Pathway. Front Pharmacol. 2021;12:793107. 9. Dong W, Liu X, Liu W, Wang C, Zhao S, Wen S, et al. Dual antiplatelet therapy improves functional recovery and inhibits inflammation after ce
- Derived from this study: PubMed 41087834Areia AL, Almeida J, Alves V, Mota-Pinto A, Sa H. Modulation of Immune Cells by Aspirin During Pregnancy. Immunology. 2026 Feb;177(2):329-338. doi: 10.1111/imm.70051. Epub 2025 Oct 14.
- Individual participant dataSharing planned: Yes. All of my research in the form of an article with the whole protocol and results
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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.
João Sargento-Freitas, PhD contact
Ana L Areia, PhD MD principal investigator
University of Coimbra
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 Aspirin and Pregnancy Complications, run by Unidade Local de Saúde de Coimbra, EPE at 1 site in Portugal.
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 4 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: looking for participants now, as of the sponsor's last update on 19 Mar 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 Portugal. 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 Ana L Areia, PhD, MD (+351917212222, analuisareia@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Evaluate the effect of Low dose aspirin (LDA) on the modulation of immunity cells (time frame: 30 weeks). The study lists 2 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 NCT06882850, which also lists 2 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 19 Mar 2025.