Low-dose Interleukin-2 After Myocardial Infarction to Investigate Effects on Tissue-resident Regulatory T Cells

Обзор

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.

Подробное описание

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:

1. 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 2. Studying the relationship between the vasculature, cardiac tissues and circulating immune cells after systemic ld-IL-2 administration.

Вмешательства

• Препарат Interleukin-2 (Aldesleukin)
  5 sequential days of treatment (1.5MIU/day subcutaneously) and, if needed, 1.5MIU/week doses until CABG surgery completed
• Процедура Standard care
  Standard care for patients with coronary artery disease undergoing CABG surgery
• Препарат Interleukin-2 (Aldesleukin)
  5 sequential days of treatment (2.0MIU/day subcutaneously) and, if needed, 2.0MIU/week doses until CABG surgery completed

Первичные конечные точки

• Compare the differences in tissue-resident Treg gene signature in patients treated with ld-IL-2 compared to control [Срок оценки: Time of surgery]
• Comparing tissue-resident Tregs to peripheral blood Tregs from the same patient to assess the differential effect of ld-IL-2 [Срок оценки: Time of surgery]

Вторичные конечные точки (4)

• Difference in inflammatory T effector cells [Срок оценки: Time of surgery]
• Difference in other immune cells [Срок оценки: Time of surgery]
• Comparing T cell receptor repertoire [Срок оценки: Time of surgery]
• Comparing tissue-resident immune cells to circulating immune cells [Срок оценки: Time of surgery]

Критерии участия

Критерии включения

• Aged over 18 years old
• Undergoing CABG surgery

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Фундаментальное исследование

Центры проведения

Великобритания · 2 центра

• Royal Papworth Hospital NHS Foundation Trust — Cambridge
• Addenbrooke's Hospital — Cambridge

Идентификаторы

NCT: NCT07610538 · A097309

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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