Lipoprotein (a) and Vascular Regenerative Cell Content
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 40
- 试验地点
- 2
- 主要终点
- Difference in the frequency or absolute number of circulating ALDHhiSSClo primitive myeloid progenitor cells between individuals with elevated Lp(a) and individuals with non-elevated Lp(a)
研究概览
简要总结
Lp(a)-VRCE is an observational, cross sectional study looking at vessel reparative stem cell content in people with and without elevated lipoprotein (a) [Lp(a)]. Specifically, the type and number of these cells in peripheral blood samples will be measured in participants with Lp(a) ≥100 nmol/L and compared to participants with Lp(a) < 100 nmol/L. Determining the presence or absence of specific cells with blood vessel repair capacity in participants with high Lp(a) will further our knowledge of potential mechanisms through which Lp(a) influences cardiovascular health.
详细描述
Lipoprotein (a) [Lp(a)] is an independent, genetically determined, causal risk factor for the development of atherosclerotic cardiovascular disease. It is estimated that 20-30% of the global population have elevated Lp(a) and recent multinational guideline endorsements strongly advise the routine measuring of Lp(a), at least once in a person's life. Current Lp(a) risk level thresholds are described as <75 nmol/L for low risk and >125 nmol/L for high risk individuals. Despite ongoing clinical trials, there exists no approved therapeutic medication to specifically lower Lp(a).
Vascular regenerative cell exhaustion (VRCE) is described as the depletion of circulating pro-vascular reparative cells responsible for angiogenesis, vasculogenesis and arteriogenesis. Evidence in recent years has implicated VRCE as a novel mechanistic factor contributing to the aberrant cardiometabolic state present in type 2 diabetes, obesity, and in people of South Asian descent. It has been demonstrated that the VRCE phenotype can be reversed by treatment with sodium glucose co-transporter 2 inhibitors or bariatric surgery.
Lp(a)-VRCE is a cross-sectional, observational, two arm study enrolling 20 patients with elevated Lp(a) (≥100 nmol/L) and 20 patients with non-elevated Lp(a) (<100 nmol/L). From peripheral blood, mononuclear cells are isolated and enumerated via a multi-parametric flow cytometry assay utilizing aldehyde dehydrogenase activity and side scatter properties. The hypothesis is that people with elevated Lp(a) have comparatively different progenitor cell phenotypes to people with normal Lp(a) levels.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Cross Sectional
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Adults ≥18 years of age and ≤80 years of age who meet either of the following criteria:
- •Elevated Lp(a) (defined as greater than or equal to 100 nmol/L)
- •Non-elevated Lp(a) (defined as less than 100 nmol/L)
- •Willing and able to provide written informed consent and comply with study procedures.
排除标准
- •Unable or unwilling to provide written informed consent or provide a peripheral blood sample.
- •Any life-threatening disease expected to result in death within two years of consent.
- •Any malignancy not considered cured (except basal cell carcinoma of the skin). An individual is considered cured if there has been no evidence of cancer recurrence for the five years prior to screening.
- •Uncontrolled hypertension.
- •New York Heart Association Class IV heart failure.
- •Active liver disease or liver dysfunction.
- •Active kidney disease or kidney dysfunction.
- •History of hemorrhagic stroke or other major bleeding disorder.
- •White blood cell count ≥15 x 10^9/L.
- •Women who are pregnant or nursing.
- •Previously received ribonucleic acid therapy specifically targeting Lp(a).
- •Active infectious disease requiring systemic antibiotic or anti-viral agents.
- •Known acquired immunodeficiency syndrome, such as human immunodeficiency virus.
- •On oral steroid therapy (e.g., prednisone or other corticosteroids) or other immunosuppressive agents (e.g., methotrexate).
- •Treated autoimmune disorders.
- •Participating in another study/trial that is likely to affect the primary outcome.
结局指标
主要结局
Difference in the frequency or absolute number of circulating ALDHhiSSClo primitive myeloid progenitor cells between individuals with elevated Lp(a) and individuals with non-elevated Lp(a)
时间窗: Baseline
次要结局
- Difference in the frequency/absolute count of ALDHhiSSCmid monocytes between individuals with elevated Lp(a) and individuals with non-elevated Lp(a)(Baseline)