The Impact of Aspirin Dose Modification on the Innate Immune Response - Will Lower Dose Aspirin Therapy Reduce the Response to Endotoxin

• Status: Recruiting
• Trial end date: 2022-03-31
• Target enrollment: 0
• Participant gender: All

Summary

Heart attacks are usually caused by clots in a coronary artery, depriving the heart muscle of blood. Platelets are the main type of blood cell causing clots to form and physicians typically give a combination of two anti-platelet drugs, aspirin and ticagrelor, to treat this. However, aspirin and ticagrelor have effects not just on the platelets but also on the immune system. The investigator has been investigating the effects of different doses of aspirin in heart attack participants when taken alongside ticagrelor, and have found that a new, lower dose of aspirin given twice daily, rather than the usual standard dose once daily, reduces the tendency to bleed whilst on treatment. The investigators are hoping to study the wider effects of different aspirin doses, with and without ticagrelor, and have therefore developed this study.

During the two periods of the study, the investigator will give healthy volunteers a combinations of these medications and then stimulate their immune system, in order to see if the medications affect the immune response. The study will involve a period of medication for 10-14 days followed by a day in hospital stimulating the immune system with an injection into the bloodstream of a substance known as endotoxin, which causes temporary flu-like symptoms, followed by blood and urine tests. The investigator will then repeat the process, after a minimum of five weeks, taking a different medication combination and having a further endotoxin injection. The investigator will also keep in contact by telephone until 2 weeks after the end of the medication to ensure participant remain well.

• Phase: Phase 4
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Sheffield Teaching Hospitals NHS Foundation Trust
• Treatments: Aspirin; Ticagrelor

Criteria

Inclusion Criteria:

• Healthy male subjects, or female subjects not of childbearing potential (either surgically sterile or post-menopausal)]

• Age between 18 and 65 years inclusive

• Non-smokers

• Body mass index (BMI) between 18 and 28 kg/m2 inclusive, with a body weight between 60-100 kg

• In good health as determined by a medical history, physical examination, vital signs and clinical laboratory test results, including renal and liver function, and full blood count

• Provision of informed consent before any trial-related activity

Exclusion Criteria:

• Any history of cancer, diabetes or, in the opinion of the investigator, clinically-significant cardiovascular, respiratory, metabolic, renal, hepatic, gastrointestinal, haematological, dermatological, neurological, psychiatric or other major disorders

• Any history of either significant multiple drug allergies or known allergy to the study drugs or any medicine chemically related to the study drugs

• A clinically-significant illness within 4 weeks of randomisation

• Any clinically-significant abnormal laboratory test results at screening in the opinion of the investigator

• A supine blood pressure at screening, after resting for 5 minutes, higher than 150/90 mmHg or lower than 105/65 mmHg

• A supine heart rate at screening, after resting for 5 minutes, outside the range of 50-100 beats/min

• Receipt of any prescribed or over-the-counter systemic or topical medication within 48 hours prior to the start of dosing

• Planned or expected requirement, during the next 3 months (at randomisation, or 3 weeks at the start of period 2), for any systemic or topical prescribed drug, or for systemic or topical over-the-counter NSAID, corticosteroid, anthihistamine or any other drug that could affect inflammation, thrombosis or haemostasis in the opinion of the investigator.

• Receipt of an investigational medicinal product within the previous four months (new chemical entity) or three months (licensed product) or subjects who have received a vaccine within three weeks preceding the start of dosing. When reconfirming eligibility at the start of period 2, receipt of aspirin, ticagrelor or endotoxin during period 1 of this study will not be counted for this purpose.

• Any donation of blood or plasma in the month preceding the start of dosing.

• A history of alcohol or drug abuse

• Mental incapacity or language barriers that preclude adequate understanding