Type 2 diabetes Nutritional, Metabolic, Endocrine
Conditions
Interventions
We hypothesise that P2Y12 inhibitors and aspirin will differentially modulate the deleterious proinflammatory and prothrombotic consequences of experimental hypoglycaemia in type 2 diabetes (T2D) with
Sponsors
Sheffield Teaching Hospitals NHS Foundation Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Provision of informed consent prior to any study-specific procedures 2. Male or female aged between 18 and 65 years old 3. Confirmed diagnosis of T2D taking oral hypoglycaemic agents and/or glucagon-like peptide 1 analogs/insulin: participants treated with insulin will be eligible if the duration of treatment with insulin is 2 years 4. Screening glycated haemoglobin A1c (HbA1c) 6.5-10.5% (48-91 mmol/mol), if the screening HbA1c is outside this range then participants will be ineligible
Exclusion criteria
Exclusion criteria: 1. History of previous myocardial infarction or any other acute coronary syndrome event, ischaemic heart disease as a clinical diagnosis and/or proven through percutaneous coronary intervention (PCI) and/or cardiac imaging modalities 2. History of cardiac arrhythmia other than ectopic beats 3. History of heart failure (clinical diagnosis and/or based on echocardiographic findings) 4. History of peripheral vascular disease (clinical diagnosis and/or based on vascular imaging studies) 5. History of stroke (haemorrhagic or ischaemic) 6. History of transient ischaemic attack (TIA) 7. Significant visual impairment due to retinopathy in the opinion of the investigator, untreated stage 3 or above diabetic retinopathy, evidence of active retinal haemorrhage as determined by ongoing treatment and/or ophthalmology follow up 8. Diabetic nephropathy defined as an album-to-creatinine ratio > 30 mg/mmol on routine clinical tests performed within the last year or an estimated glomerular filtration rate <30 ml/min/1.73m2 on bloods performed at screening 9. Clinically significant abnormality on resting 12-lead ECG, including a resting heart rate outside the range of 50-100 beats per minute but excluding atrial or ventricular ectopic beats on an ECG performed at screening 10. Significant symptoms suggestive of CV disease 11. Known untreated hyperthyroidism 12. Epilepsy or previous seizures 13. Participants on blockers or QT interval prolonging drugs 14. Cardiac autonomic neuropathy as measured at screening 15. Serious intercurrent illness within the last 6 weeks 16. Previous history of deep vein thrombosis or pulmonary embolism 17. Any active malignant disease (under active treatment and/or oncology follow-up) or a history of any malignant disease in the last 5 years 18. Family history of sudden death 19. Inability to communicate in English 20. Treatment or planned treatment with antiplatelet (including aspirin, prasugrel, clopidogrel, ticagrelor, dipyridamole, cilostazol, or glycoprotein IIb/IIIa antagonists), anti-inflammatory/immunomodulatory (oral, topical or inhaled corticosteroids; disease-modifying anti-rheumatic drugs; immunosuppressants; chemotherapy drugs; oral or topical antihistamines) anticoagulant medications (warfarin, dabigatran, rivaroxaban, edoxaban, apixaban, parenteral anticoagulants) or fibrinolytic agents within 2 months of randomisation 21. Any planned surgery or other procedure that may require suspension or discontinuation of trial medication expected to occur within 2 months of randomisation 22. Current or planned use of a non-steroidal anti-inflammatory drug 23. Known hypersensitivity to aspirin, salicylic acid (including certain asthma patients who may suffer an asthma attack or faint), prasugrel or excipients 24. Clinically significant liver disease, defined as known or suspected diagnosis of hepatic cirrhosis with current Child-Pugh class B or C; or elevation of serum alanine transferase or aspartate transferase greater than 3 times the upper limit of the normal range for the processing laboratory on bloods performed at screening 25. Abnormal clotting profile on screening that in the opinion of the investigator, would preclude safe involvement in the study or compromise its scientific credibility 26. Abnormal full blood count on screening that in the opinion of the investigator, would preclude safe involvement in the study or compromise its scientific credibility 27. Evidence of active pathological bleeding or peptic ulc
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The increase in pre-treatment baseline plasma IL-6 levels measured using enzyme-linked immunosorbent assay (ELISA) in participants with T2D receiving prasugrel (10 mg or 5 mg orally/day according to body weight) compared with aspirin (75 mg orally/day) at 60 minutes of recovery (180 minutes clamp time point) following 60 minutes of hyperinsulinaemic-hypoglycaemia at 2.5 mmol/l | — |
Secondary
| Measure | Time frame |
|---|---|
| Changes in the levels of: 1. Inflammatory cytokines measured using ELISA 2. White cell kinetics measured using a clinical grade haematology analyser 3. Platelets measured using impedance aggregometry 4. Thrombus formation measured using multi-colour flow cytometry - in participants with T2D receiving prasugrel (10 mg or 5 mg orally/day according to body weight) or with aspirin (75 mg orally/day) compared with no antiplatelet drugs in the medication period from 0 to 180 minutes clamp time points | — |
Countries
England, United Kingdom
Outcome results
None listed