Clinical trial NCT05975554: The Effect of Low-dose Interleukin-2 on the Immune Landscape of Human Atherosclerotic Plaques at Single Cell Resolution.
Official title: The Effect of Low-dose Interleukin-2 on the Immune Landscape of Human Atherosclerotic Plaques at Single Cell Resolution.
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: TIA
Carotid Artery Plaque
Carotid Atherosclerosis
Keywords: Interleukin-2
IL-2
TIA
Carotid Stenosis
Lead sponsor: Cambridge University Hospitals NHS Foundation Trust
Sponsor class: OTHER
First posted: 2023-08-04
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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

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

Primary outcomes:
measure: Difference in gene expression in Tregs
timeFrame: Time of surgery
Secondary outcomes:
measure: Difference in gene expression in Teff cells.
timeFrame: Time of surgery
measure: Immune cell gene signature, in plaque and blood.
timeFrame: Time of surgery
measure: Difference in gene expression patterns in Treg & Teff cells.
timeFrame: Baseline and at time of surgery
Other outcomes:
measure: Other immune cell and vascular smooth muscle cell gene expression
timeFrame: Time of surgery
measure: Ligand-receptor interactions.
timeFrame: Time of surgery
measure: T-Cell receptor profile
timeFrame: Time of surgery
measure: Inflammatory pathway activation.
timeFrame: Time of surgery
Locations:
city: Cambridge
country: United Kingdom
facility: Addenbrookes Hospital
state: Cambridgeshire
Study officials:
References: