Low-dose Interleukin-2 After Myocardial Infarction to Investigate Effects on Tissue-resident Regulatory T Cells
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 24
- 试验地点
- 2
- 主要终点
- Compare the differences in tissue-resident Treg gene signature in patients treated with ld-IL-2 compared to control
研究概览
简要总结
The primary goals of this study are to compare the differences in tissue-resident Treg gene signature for activation, proliferation, and suppressive function using single-cell/-nucleus RNA sequencing in patients treated with ld-IL-2 compared to control grouped by individual tissue beds from in and around the heart. Additionally, tissue-resident Tregs will be compared to peripheral blood Tregs from the same patient to assess the differential effect of ld-IL-2 on the two compartments.
详细描述
So far, our lab has looked at Tregs and immune cells in the blood. The question remained whether ld-IL-2 can have the desired effect on Tregs in tissues, particularly the vasculature and cardiac tissues, where they could promote tissue repair and potentially improve clinical outcomes for patients after a myocardial infarction which causes significant tissue damage. Clinically, this could lead to lower rates of heart failure.
In both the LILACS and IVORY trials, the effect measured was on circulating Tregs, whilst the effect of ld-IL-2 on tissue resident immune cells remains unknown.
Therefore, the aims of the study are to understand the effect of treatment with ld-IL-2 on tissue-resident immune cells in the context of ischaemic heart disease and acute MI where there has been acute tissue damage. This includes:
- Assessment if ld-IL-2, given systemically to patients at our proposed doses, can alter Tregs in the vasculature and cardiac tissues to exhibit a tissue repair and anti-inflammatory phenotype
- Studying the relationship between the vasculature, cardiac tissues and circulating immune cells after systemic ld-IL-2 administration.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Aged over 18 years old
- •Undergoing CABG surgery
排除标准
- •Critical left main stem coronary disease
- •Severe valvular disease (for example 'severe' aortic stenosis as classified on echocardiogram report)
- •Haemodynamic instability caused by arrhythmia requiring cardioversion in the current admission
- •Non-sustained ventricular tachycardia of >10 beats in the last 48 hours
- •Autoimmune disease
- •Any regular immunosuppressive treatment [Inhaled or topical steroids are permissible]
- •Known active hepatic disease or alanine aminotransferase (ALT) > 3xULN
- •Severe chronic kidney disease (defined as eGFR < 30 ml/min/1.73m2)
- •Allergy or intolerance to aldesleukin
- •Signs and symptoms of active infection
- •History of human immunodeficiency virus (HIV), hepatitis B or C
- •Current malignancy requiring active treatment
- •Vaccine within 4 weeks prior to screening
- •Women of child-bearing potential and pregnancy (women must be either postmenopausal (defined as being amenorrhoeic for greater than 2 years with an appropriate clinical profile (e.g. age appropriate (>55 years old), history of vasomotor symptoms) or having documented hysterectomy and/or bilateral oophorectomy)
- •Women who are breast-feeding
- •Clinically relevant medical or surgical conditions that, in the opinion of the investigator, would put the subject at risk by participating in the study
研究组 & 干预措施
Low dose interleukin-2 at dose 1.5MIU
Commercially available aldesleukin with a UK marketing authorisation will be used and will be initially prepared as per SmPC. Dose of 1.5MIU will be used for all daily and, if needed, weekly doses
干预措施: Standard care (Procedure)
Low dose interleukin-2 at dose 2.0MIU
Commercially available aldesleukin with a UK marketing authorisation will be used and will be initially prepared as per SmPC. Dose of 2.0MIU will be used for all daily and, if needed, weekly doses
干预措施: Standard care (Procedure)
Control
Standard of care treatment
干预措施: Standard care (Procedure)
Low dose interleukin-2 at dose 2.0MIU
Commercially available aldesleukin with a UK marketing authorisation will be used and will be initially prepared as per SmPC. Dose of 2.0MIU will be used for all daily and, if needed, weekly doses
干预措施: Interleukin-2 (Aldesleukin) (Drug)
Low dose interleukin-2 at dose 1.5MIU
Commercially available aldesleukin with a UK marketing authorisation will be used and will be initially prepared as per SmPC. Dose of 1.5MIU will be used for all daily and, if needed, weekly doses
干预措施: Interleukin-2 (Aldesleukin) (Drug)
结局指标
主要结局
Compare the differences in tissue-resident Treg gene signature in patients treated with ld-IL-2 compared to control
时间窗: Time of surgery
Assessing Tregs from the various tissue beds and comparing differential gene expression markers for tissue healing and inflammation using sc/snRNA-sequencing technologies
Comparing tissue-resident Tregs to peripheral blood Tregs from the same patient to assess the differential effect of ld-IL-2
时间窗: Time of surgery
Comparing the tissue Tregs against blood Tregs from the same patient by comparing differential gene expression markers for tissue healing and inflammation using sc/snRNA-sequencing technologies and looking for differences between the two compartments.
次要结局
- Comparing tissue-resident immune cells to circulating immune cells(Time of surgery)
- Difference in inflammatory T effector cells(Time of surgery)
- Difference in other immune cells(Time of surgery)
- Comparing T cell receptor repertoire(Time of surgery)
研究者
Tian Zhao
BHF Intermediate Fellow
Cambridge University Hospitals NHS Foundation Trust