Mechanistic Study of Anti-Platelet Therapy in Atherosclerosis

NCT07169513 | Not Yet Recruiting

• 1 other identifier: 174661
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Many people have a higher chance of getting heart problems. These individuals include people who are very overweight (obesity), have high blood pressure (hypertension), diabetes, or other health concerns. Heart problems often happen because of a condition called atherosclerosis. This condition is when the arteries, which are the blood vessels carrying blood from the heart, become hard and inflamed (swollen and irritated) at the same time. Atherosclerosis causes arteries narrowing, making it harder for blood to flow through. The signs of atherosclerosis can be mild, like feeling chest pain (called angina) because the heart isn't getting enough blood. In more serious cases, it can lead to a heart attack. Think of inflammation as the body's natural alarm system. When a person gets hurt or sick, the body releases special chemicals. These chemicals tell the immune system (the body's defence team) to come and help. Their job is to heal the injury or fight off the infection. While inflammation is usually good, sometimes it can go wrong. Atherosclerosis is one of these conditions where the inflammation in the blood vessels becomes abnormal. This ongoing inflammation can harm the body and lead to various heart problems and other health issues not directly related to the heart. In atherosclerosis, platelets (cell fragments in our blood that form clots and stop or prevent bleeding) bind to monocytes (a type of white blood cell and a type of phagocyte - part of the immune system) to form clusters called monocyte platelet aggregate (MPA). Studies have shown that people with atherosclerosis have higher levels of the monocytes clustering with the platelets. This aggregate contributes to the worsening of atherosclerosis. Additionally, this aggregate can predict the risk of developing various cardiac diseases. Anti-platelet (anti-clotting) medications work by stopping platelet function. In this study, investigators are giving participants two different anti-platelet medications to study the effect of these medications on the level of MPA. The target people of our study are the people with silent atherosclerosis (there is an accumulation of lipids in the blood vessels but no signs or symptoms). No existing research demonstrates whether the two most commonly prescribed anti-platelets (aspirin and clopidogrel) can help reduce MPA levels. This study aims to show the effect of anti-platelet medications on the level of MPA and other inflammatory indicators. The two medications are aspirin and clopidogrel. These two drugs are already available in the market and widely used by different patients for different reasons. Aspirin and clopidogrel have different modes of action to stop platelet function.

Conditions

Peripheral Arterial Disease; Silent Atherosclerosis

Outcome Measures

Primary Outcomes (1)

• Monocyte-platelet aggregates (MPAs)

  Changes in the percentages of monocyte-platelet aggregates (MPAs) in two groups of patients following treatment with aspirin and clopidogrel using flow cytometry

  Maximum 14 weeks

Secondary Outcomes (3)

• Monocyte and platelet activation/phenotype

  Maximum 14 weeks

• Circulating mediators of inflammation

  Maximum 14 weeks

• Gene expression

  Maximum 14 weeks

Study Arms (2)

Aspirin/Clopidogrel

ACTIVE COMPARATOR

Drug: Aspirin 75 mg daily; Drug: Clopidogrel 75 mg daily

Clopidogrel/DAPT

ACTIVE COMPARATOR

Drug: Clopidgrel 75 mg daily; Drug: Aspirin 75 mg daily + Clopidgrel 75 mg daily

Interventions

Aspirin 75 mg daily DRUG

For group 1 patients

Aspirin/Clopidogrel

Clopidogrel 75 mg daily DRUG

For group 2 patients

Aspirin/Clopidogrel

Clopidgrel 75 mg daily DRUG

For group 1 patients

Clopidogrel/DAPT

Aspirin 75 mg daily + Clopidgrel 75 mg daily DRUG

For group 2 patients

Clopidogrel/DAPT

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Group 1:
• Male or female age 18 years or older
• Willing to participate in the study, and able to give informed consent
• Negative pregnancy test for a childbearing age woman
• Receiving standard of care
• Confirmed atherosclerotic cardiovascular risk based on clinical assessment
• Group 2:
• Male or female age 18 years or older
• Willing to participate in the study, and able to give informed consent
• Receiving standard of care
• Negative pregnancy test for a childbearing age woman
• Confirmed diagnosis of peripheral arterial disease (ankle-brachial index below 0.9) with Rutherford grade 1-3.

You may not qualify if:

• Group 1:
• Diabetes
• Receiving any anti-platelet medications within the last two weeks
• Receiving any anticoagulant medications within the last two weeks
• Receiving statin medications within the last two weeks
• Known major organ dysfunction
• Significant co-morbidities
• Pregnancy or lactating woman
• Unwilling, or unable to give informed consent
• Presence of co-existing autoimmune disease
• Hypersensitivity to aspirin or clopidogrel
• Severe hepatic impairment (Child-Pugh grade C)
• Active peptic ulcer
• Presence of co-existing inflammatory or autoimmune diseases
• Frequent use of medications known to affect platelet function five days before baseline phlebotomy and during the study

Sponsors & Collaborators

• Guy's and St Thomas' NHS Foundation Trust: lead
• King's College London: collaborator

Study Sites (1)

Guy's and St Thomas' NHS Foundation Trust

London, SE1 7EH, United Kingdom

Location

MeSH Terms

Conditions

Peripheral Arterial Disease

Interventions

Aspirin; Clopidogrel

Condition Hierarchy (Ancestors)

Atherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Peripheral Vascular Diseases

Intervention Hierarchy (Ancestors)

Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Ticlopidine; Thienopyridines; Thiophenes; Sulfur Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Central Study Contacts

Ashish Patel

CONTACT

0442071880216; ashish.patel@kcl.ac.uk

Eman Al Musalami

CONTACT

eman.1.al_musalami@kcl.ac.uk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The study is a randomised, single-blind, controlled crossover trial in two groups of patients following treatment with aspirin and clopidogrel; (1) patients with abnormally high carotid intima-media thickness (cIMT) - defined by an intima-media thickness (IMT) above the 75th centile for age and sex; and (2) patients with a confirmed diagnosis of PAD (ankle-brachial index below 0.9) with Rutherford classification grade of 1-3.

Study Record Dates

• First Submitted: July 4, 2025
• First Posted: September 11, 2025
• Study Start: October 1, 2025
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2026
• Last Updated: September 11, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)