Aspirin and Neutrophils in Preeclampsia

Pregnancy Clinical Trial

Official title:

Investigating the Role of Neutrophils in Aspirin Treatment for Women at High Risk of Preeclampsia

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04974892
• Other study ID #: IRAS 294761
• Status: Active, not recruiting
• Start date: April 1, 2022
• Est. completion date: April 30, 2025

Study information

• Verified date: February 2024
• Source: Queen Mary University of London
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

The exact mechanisms by which aspirin prevents the development of preeclampsia in high-risk patients are currently not fully known. Furthermore, a small proportion of high-risk patients who are on low-dose aspirin (LDA) still go on to develop preeclampsia (PE).

This longitudinal observational study will assess the immune profile in participants who are taking low dose aspirin (LDA) in pregnancy. As part of routine care, patients at high risk of developing preeclampsia are treated with LDA from 16 weeks gestation.

The study will be conducted at Barts Health National Health Service (NHS) Trust. The study population will comprise of 2 groups of participants:

1. Those who respond to LDA and do not develop preeclampsia (responders)

2. Participants who do not respond to LDA and develop preeclampsia (non responders)

Participants will be consented at their booking appointment. Participants will be eligible if they have a singleton pregnancy and are aged over 18 years. They will have an additional blood sample taken at 12, 20, 28 and 36 weeks gestation.

The blood samples will be tested to assess immune cell function, metabolism and genetics. This will identify cumulative changes in immunobiology at key time points in pregnancy.

Description:

The exact mechanisms by which aspirin prevents the development of PE in high-risk patients are currently not fully known. Furthermore, a small proportion of high-risk patients who are on low-dose aspirin still go on to develop PE. This is a big unmet need because although it is known that this treatment is working for some patients, it is not known how it's working in these patients and also why a proportion of patients don't respond to this treatment. If the key mechanisms by which aspirin treatment is beneficial in patients at high risk of PE can be identifies, this will lead to better information for clinicians of why this treatment works and this could then be conveyed to the patient. Moreover, if key differences can be identified between aspirin responders and non-responders, novel therapeutic targets could be developed that could work for all patients at high risk of PE.

One of the main anti-inflammatory actions of aspirin is the release of aspirin-triggered lipoxin (ATL). The receptor for ATL (FPR2/ALX) is highly expressed on neutrophils, suggesting that the anti-inflammatory action of this drug is mediated via neutrophils. The investigators have previously shown that neutrophils are important in mediating anti-inflammatory responses in PE. Thus, taken together, the hypothesis is that neutrophils are key to understanding the mechanisms involved in the use of low-dose aspirin (LDA) treatment in patients at high risk of developing PE and key to understanding why this treatment does not work in some high-risk patients. This hypothesis will be addressed by two objectives both of which will entail in-depth profiling of neutrophils.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 60
• Est. completion date: April 30, 2025
• Est. primary completion date: March 31, 2025
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion criteria

• Age 18-60 years

• Singleton pregnancy

• Live fetus at 11-13 weeks of gestation

• Informed, written consent

• Upper age of 60 years

• Patient taking low dose aspirin as standard of care

Exclusion criteria

• Unwilling or unable to give consent

• Participants who are unable to understand written English

Related Conditions & MeSH terms

• Immunology
• Pre-Eclampsia
• Preeclampsia
• Pregnancy

Intervention

Diagnostic Test:
• Blood test
Blood tests will be taken at 12, 20, 28 and 36 weeks gestation to assess the immune profile and omic profile.

Locations

Country	Name	City	State
United Kingdom	Barts Health NHS Trust, The Royal London Hospital	London

Sponsors (1)

Lead Sponsor	Collaborator
Queen Mary University of London

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To longitudinally define the neutrophil profile in high-risk patients given low dose aspirin (LDA) at =16 weeks.	To address the first objective, to assess the neutrophil profile in high-risk patients given LDA at =16 weeks, a longitudinal analyses will be undertaken of neutrophils taken from participants at high-risk of PE (as identified at their pregnancy booking appointment). The first blood test will occur prior to aspirin commencement and be repeated at 3 other time points in pregnancy. These longitudinal analyses will identify cumulative changes in neutrophils following the commencement of aspirin treatment and pinpoint key timepoints of aspirin on neutrophil biology.	2 years
Primary	To define the neutrophil profile in a cohort of high-risk patients who have not responded to low dose aspirin (LDA) and have gone on to develop PE.	To address the second objective (to assess the neutrophil profile in a cohort of high-risk patients who have not responded to LDA and have gone on to develop PE), 20 LDA non-responders subsequently develop PE will be identified.	2 years