The Effect of Low-dose Interleukin-2 on the Immune Landscape of Human Atherosclerotic Plaques at Single Cell Resolution. (ELLIPSE)

NHS Foundation Trust

Status: Active, not recruiting

Conditions: TIA; Carotid Artery Plaque; Carotid Atherosclerosis

Treatments: Drug: Interleukin-2 [IL-2]; Procedure: Standard care - Carotid Endarterectomy

Study type: Interventional

Funder types: Other

Identifiers

NCT05975554

A096090

Details and patient eligibility

About

The goal of this clinical trail is to compare the differences in carotid plaque Treg cells' gene signature for activation, proliferation, and suppressive function using scRNA-seq in patients treated with IL-2 compared to control.

Full description

Up till now our Lab has looked at Tregs and immune cells in the blood. The question remains whether low dose IL-2 can have the desired effect on Tregs in atherosclerotic plaques where they could alter the pathophysiology and potentially clinical outcomes for patients.

Up until recently, the cellular composition and cell-specific expression patterns of human atherosclerotic plaques remained elusive. However, recent breakthroughs studies using scRNA-seq, CITE-seq, and single-cell ATAC-seq on human carotid plaques have offered important insight into plaque composition, cell heterogeneity, and cell-cell interactions giving new perspectives on mechanisms of disease. The next logical stage is to use this new insight and powerful biological tool to assist in drug development for patients.

Therefore, the aims of the study are:

1. To assess if low dose IL-2, given systemically to patients at our proposed dose, can alter Tregs in atherosclerotic plaques (the disease tissue) to exhibit a proliferating, activated, and immunosuppressive phenotype
2. To assess if modulating plaque Tregs can cause a shift in the plaque immune landscape to a less inflammatory phenotype
3. To study the relationship between plaque and circulating immune cells after systemic immune modulation

Enrollment: 30 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Presence of carotid stenosis on either ultrasound or CT scan.
• Planned to undergo carotid endarterectomy.

Exclusion criteria

• Autoimmune disease
• Any regular immunosuppressive treatment [Inhaled or topical steroids are permissible]
• Modified Rankin Scale score of ≥4 at screening
• Known active hepatic disease or alanine aminotransferase (ALT) > 2xULN
• Severe chronic kidney disease (defined as eGFR < 30 ml/min/1.73m2)
• Allergy or intolerance to aldesleukin
• Signs or 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 or plans for vaccination during study period
• Women of child-bearing potential and pregnancy
• Women who are breast-feeding
• Clinically relevant medical or surgical conditions that, in the opinion of the

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

30 participants in 2 patient groups

Low dose interleukin-2

Experimental group

Description:

Commercially available aldesleukin with a UK marketing authorisation will be used and will be initially prepared as per SmPC.

Treatment:

Procedure: Standard care - Carotid Endarterectomy

Drug: Interleukin-2 [IL-2]

Control

Active Comparator group

Description:

Standard of care treatment

Treatment:

Procedure: Standard care - Carotid Endarterectomy