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

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.

Study Overview

• Status: Recruiting
• Conditions: Coronary Artery Disease; CABG; Myocardial Infarction (MI)
• Intervention / Treatment: Drug: Interleukin-2 (Aldesleukin); Procedure: Standard care; Drug: Interleukin-2 (Aldesleukin)

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • Cambridgeshire
    • Cambridge, Cambridgeshire, United Kingdom, CB2 0QQ
      • Recruiting
      • Addenbrooke's Hospital
      • Contact: Ali Al-Hadithi, MB BChir; Phone Number: 01223768678; Email: abaka2@cam.ac.uk
    • Cambridge, Cambridgeshire, United Kingdom, CB2 0AY
      • Recruiting
      • Royal Papworth Hospital NHS Foundation Trust
      • Contact: Ali Al-Hadithi, MB BChir; Phone Number: 01223768678 Royal Papworth Hospital NHS Fo; Email: abaka2@cam.ac.uk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Aged over 18 years old
• Undergoing CABG surgery

Exclusion Criteria:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Control; Standard of care treatment	Procedure: Standard care; Standard care for patients with coronary artery disease undergoing CABG surgery
Experimental: 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	Drug: Interleukin-2 (Aldesleukin); 5 sequential days of treatment (1.5MIU/day subcutaneously) and, if needed, 1.5MIU/week doses until CABG surgery completed; Other Names: 1.5MIU; Procedure: Standard care; Standard care for patients with coronary artery disease undergoing CABG surgery; Drug: Interleukin-2 (Aldesleukin); 5 sequential days of treatment (2.0MIU/day subcutaneously) and, if needed, 2.0MIU/week doses until CABG surgery completed; Other Names: 2.0MIU
Experimental: 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	Drug: Interleukin-2 (Aldesleukin); 5 sequential days of treatment (1.5MIU/day subcutaneously) and, if needed, 1.5MIU/week doses until CABG surgery completed; Other Names: 1.5MIU; Procedure: Standard care; Standard care for patients with coronary artery disease undergoing CABG surgery; Drug: Interleukin-2 (Aldesleukin); 5 sequential days of treatment (2.0MIU/day subcutaneously) and, if needed, 2.0MIU/week doses until CABG surgery completed; Other Names: 2.0MIU

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Compare the differences in tissue-resident Treg gene signature in patients treated with ld-IL-2 compared to control	Assessing Tregs from the various tissue beds and comparing differential gene expression markers for tissue healing and inflammation using sc/snRNA-sequencing technologies	Time of surgery
Comparing tissue-resident Tregs to peripheral blood Tregs from the same patient to assess the differential effect of ld-IL-2	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.	Time of surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in inflammatory T effector cells	Comparing differential gene expression using sc/snRNA-sequencing technologies from isolated effector T cells between the 3 patient groups (control, 1.5MIU and 2.0MIU)	Time of surgery
Difference in other immune cells	Comparing differential gene expression using sc/snRNA-sequencing technologies from other immune cells (e.g. B cells) between the 3 patient groups (control, 1.5MIU and 2.0MIU)	Time of surgery
Comparing T cell receptor repertoire	Comparing differences in T cell receptor (TCR) repertoire using TCR sequencing technologies between the 3 patient groups (control, 1.5MIU and 2.0MIU)	Time of surgery
Comparing tissue-resident immune cells to circulating immune cells	Tissue-resident immune cells will be compared to peripheral/circulating immune cells from the same patient using sc/snRNA-seq technologies to compare the differential effect of ld-IL-2 on the two compartments.	Time of surgery

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Systemc biomarkers of inflammation and tissue damage	Compare blood-based inflammation markers and assays between the three patient groups (control, 1.5MIU, 2.0MIU)	Time of surgery
Non-immune cells and cardiomyocytes	Compare stromal and myocardial cells on sc/snRNA-seq technologies between the three patient groups (control, 1.5MIU, 2.0MIU)	Time of surgery
Characterise tissue-level gene signatures	Tissue-level RNA expression will be evaluated on sc/snRNA-sequencing technologies	Time of surgery
Gut microbiota	Compare stool-based analysis of microbiota between the three patient groups (control, 1.5MIU, 2.0MIU)	Time of surgery
Safety and tolerability of IL-2 in patients after acute MI undergoing CABG	Safety and tolerability will be assessed by recording adverse events (AEs) and reviewing patient notes.	Time of surgery

Collaborators and Investigators

• Sponsor: Cambridge University Hospitals NHS Foundation Trust
• Collaborators: Royal Papworth Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 31, 2026
• Primary Completion (Estimated): November 1, 2028
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: May 20, 2026
• First Submitted That Met QC Criteria: May 20, 2026
• First Posted (Actual): May 28, 2026

Study Record Updates

• Last Update Posted (Actual): May 28, 2026
• Last Update Submitted That Met QC Criteria: May 20, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Myocardial infarction; CABG; Coronary artery bypass graft; IL-2; Interleukin-2; MI
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Infarction; Necrosis; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Myocardial Ischemia; Ischemia; Pathological Conditions, Signs and Symptoms; Coronary Artery Disease; Myocardial Infarction; Health Services Administration; Health Care Quality, Access, and Evaluation; Quality of Health Care; Quality Indicators, Health Care; Standard of Care; aldesleukin
• Other Study ID Numbers: A097309

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No