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NCT Number: NCT05975554

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

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.

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This study is active but is not currently recruiting participants.

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Key information

Conditions

TIA Arterial Occlusive Diseases Brain Diseases Cardiovascular Diseases Carotid Artery Diseases Carotid Artery Plaque Carotid Atherosclerosis Carotid Stenosis Central Nervous System Diseases Cerebrovascular Disorders Nervous System Diseases Vascular Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Addenbrookes Hospital

Cambridge, Cambridgeshire, CB2 0QQ, United Kingdom

About this study

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:

  • 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
  • To assess if modulating plaque Tregs can cause a shift in the plaque immune landscape to a less inflammatory phenotype
  • To study the relationship between plaque and circulating immune cells after systemic immune modulation

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Interleukin-2 [IL-2]

Drug

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

Standard care - Carotid Endarterectomy

Procedure

Standard care for patients with carotid stenosis undergoing carotid endarterectomy

Primary outcomes

  1. Difference in gene expression in Tregs

    Time frame: Time of surgery

    Comparing differential gene expression using scRNA-seq technologies, from isolated Tregs from carotid plaques from the two patient groups (IL-2 treatment and control). Differential gene expression will be assessed using standard techniques (Z-Score)

Secondary outcomes

  1. Difference in gene expression in Teff cells.

    Time frame: Time of surgery

    Comparing differential gene expression using scRNA-seq technologies, from isolated Teffs from carotid plaques from the two patient groups (IL-2 treatment and control). Differential gene expression will be assessed using standard techniques (Z-Score)

  2. Immune cell gene signature, in plaque and blood.

    Time frame: Time of surgery

    Difference in immune cell gene signature will be compared using scRNA-seq in both plaque and blood samples, and further compared between IL-2 and control groups. Comparative analysis will be completed using gene set enrichment analysis (Enrichment Score).

  3. Difference in gene expression patterns in Treg & Teff cells.

    Time frame: Baseline and at time of surgery

    Comparison between Treg and Teff cells collected at baseline and day of surgery will be compared between IL-2 and control groups. Differential gene expression will be assessed using standard techniques (Z-Score)

Other outcomes

  1. Other immune cell and vascular smooth muscle cell gene expression

    Time frame: Time of surgery

    As per primary outcome measure but in immune cells and vascular smooth muscle cells (excluding Treg & Teff cells). Differential gene expression will be assessed using standard techniques (Z-Score)

  2. Ligand-receptor interactions.

    Time frame: Time of surgery

    Differential regulation of ligand-receptor interactions between control and IL-2 treated cells will be identified by comparing single-cell/single-cell ligand-receptor interaction scores for the two groups. This measure is descriptive in nature.

  3. T-Cell receptor profile

    Time frame: Time of surgery

    Difference in TCR clonality in plaques between the two groups will be assessed from clonotypes based on identical V-J gene usage and identical CDR3 junctions.

  4. Inflammatory pathway activation.

    Time frame: Time of surgery

    Activation of inflammatory pathways both at plaque and systemic level. Assess for enrichment of genes involved in inflammatory pathways - enrichment score.

Sponsors and collaborators

Lead sponsor

Cambridge University Hospitals NHS Foundation Trust

Other

Registry information

Acronym: ELLIPSE

Important dates

Study start
2023
Primary completion
2025
Study completion
2025
First posted
Aug 4, 2023
Registry last updated
May 30, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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