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Aspirin and Neutrophils in Preeclampsia

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ClinicalTrials.gov Identifier: NCT04974892
Recruitment Status : Not yet recruiting
First Posted : July 23, 2021
Last Update Posted : August 4, 2021
Sponsor:
Information provided by (Responsible Party):
Queen Mary University of London

Brief 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.


Condition or disease Intervention/treatment
Preeclampsia Neutrophil Immunology Pregnancy Diagnostic Test: Blood test

Detailed 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.

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Study Type : Observational [Patient Registry]
Estimated Enrollment : 60 participants
Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration: 24 Weeks
Official Title: Investigating the Role of Neutrophils in Aspirin Treatment for Women at High Risk of Preeclampsia
Estimated Study Start Date : September 1, 2021
Estimated Primary Completion Date : September 1, 2023
Estimated Study Completion Date : September 1, 2023

Resource links provided by the National Library of Medicine

Drug Information available for: Aspirin

Group/Cohort Intervention/treatment
low dose aspirin
high-risk women given LDA at ≤16 weeks.
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.

Non responders to low dose aspirin
high-risk women who have not responded to LDA and have gone on to develop PE.
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.




Primary Outcome Measures :
  1. To longitudinally define the neutrophil profile in high-risk patients given low dose aspirin (LDA) at ≤16 weeks. [ Time Frame: 2 years ]
    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. 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. [ Time Frame: 2 years ]
    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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Patients at high risk of developing preeclampsia in pregnancy who are started on low dose aspirin at ≤16 weeks.
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04974892


Locations
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United Kingdom
Barts Health NHS Trust, The Royal London Hospital
London, United Kingdom, E1 1BB
Sponsors and Collaborators
Queen Mary University of London
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Responsible Party: Queen Mary University of London
ClinicalTrials.gov Identifier: NCT04974892    
Other Study ID Numbers: IRAS 294761
First Posted: July 23, 2021    Key Record Dates
Last Update Posted: August 4, 2021
Last Verified: May 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Pre-Eclampsia
Hypertension, Pregnancy-Induced
Pregnancy Complications