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

NCT ID: NCT05975554

Last Updated: 2025-05-30

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-08-26
• Study Completion Date: 2025-09-01

Brief Summary

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.

Detailed 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

Conditions

TIA; Carotid Artery Plaque; Carotid Atherosclerosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Low dose interleukin-2

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

Group Type: EXPERIMENTAL

Interleukin-2 [IL-2]

Intervention Type: DRUG

5 sequential days of treatment (1.5MIU/day subcutaneously)

Standard care - Carotid Endarterectomy

Intervention Type: PROCEDURE

Standard care for patients with carotid stenosis undergoing carotid endarterectomy

Control

Standard of care treatment

Group Type: ACTIVE_COMPARATOR

Standard care - Carotid Endarterectomy

Intervention Type: PROCEDURE

Standard care for patients with carotid stenosis undergoing carotid endarterectomy

Interventions

Interleukin-2 [IL-2]

5 sequential days of treatment (1.5MIU/day subcutaneously)

Intervention Type: DRUG

Standard care - Carotid Endarterectomy

Standard care for patients with carotid stenosis undergoing carotid endarterectomy

Intervention Type: PROCEDURE

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Cambridge University Hospitals NHS Foundation Trust

OTHER

Sponsor Role: lead

Responsible Party

Tian Zhao

BHF Clinical Lecturer in Cardiovascular Medicine.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Addenbrookes Hospital

Cambridge, Cambridgeshire, United Kingdom

Countries

United Kingdom

Other Identifiers

A096090

Identifier Type: -

Identifier Source: org_study_id