Bone Marrow Responsiveness to Pharmacologic Mobilization of Progenitor Cells in Diabetic Versus Non-diabetic Patients
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 48
- 试验地点
- 1
- 主要终点
- CPC mobilization after a single G-CSF dose
研究概览
简要总结
Diabetes mellitus is associated with a significant reduction of circulating progenitor cells (CPCs). These include endothelial progenitor cells (EPCs), which are involved in cardiovascular homeostasis and repair. A reduction of CPCs in metabolic patients is associated with an increased risk of future adverse cardiovascular outcomes. Therefore, ways to active stimulate an increase of CPC levels in diabetes are actively pursued.
Experimental animal studies and preliminary data in humans indicate that a bone marrow defect is causally related to the low CPC level in diabetes.
Our previous data in rats indicate that diabetes reduces the bone marrow responsiveness to granulocyte colony-stimulating factor (G-CSF) in terms of progenitor cell mobilization.
In the present study, we aim at investigating bone marrow responsiveness to pharmacological mobilization of CPC in diabetic patients as compared to non-diabetic subjects.
详细描述
Diabetes mellitus is associated with a significant reduction of circulating progenitor cells (CPCs). CPCs are defined by the surface expression of the stem cell antigen CD34 and or CD133. These cells include endothelial progenitor cells (EPCs), which are involved in cardiovascular homeostasis and repair. EPCs are characterized by the co-expression of endothelial antigen(s), such as KDR.
A reduction of CPCs in metabolic patients is associated with an increased risk of future adverse cardiovascular outcomes, such as myocardial infarction, stroke, revascularization, etc. Therefore, ways to active stimulate an increase of CPC levels in diabetes are actively pursued. Indeed, there are several drugs that stimulate CPCs or EPCs, but it is not fully clear if they are active also in diabetic patients.
The mechanisms that account for CPC reduction in diabetes include defective bone marrow mobilization, reduced survival and increased homing outside the bloodstream. Experimental animal studies and preliminary data in humans indicate that a bone marrow defect is causally related to the low CPC level in diabetes.
Our previous data in rats indicate that diabetes reduces the bone marrow responsiveness to G-CSF in terms of c-kit+/Sca-1+ progenitor cell mobilization.
There is also some experimental evidence in type 2 diabetic rats that a specific form of autonomic neuropathy impairs bone marrow mobilization of progenitor cells.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 25 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Diabetes mellitus (for cases) or absence of diabetes (for controls);
- •Age 25-65;
- •Both sexes;
- •Capability of providing informed consent.
排除标准
- •Age <25 or >65;
- •Fertile women;
- •Recent (within 2 months) acute illnesses;
- •Chronic immune of infectious diseases;
- •Current or remote hematological disorders;
- •Leukocytosis, leukopenia or thrombocytopenia;
- •Organ transplantation or immune suppression;
- •Altered liver function;
- •Severe renal failure (eGFR<30 mL/min/m2);
- •Anomalies in lymphocytes subpopulations;
- •High basal level of CD34+ cell count;
- •Allergy to Filgrastim;
- •Bronchial asthma or other chronic lung disorders;
- •Current or remote cancer;
- •Deny or impossibility to provide informed consent.
研究组 & 干预措施
Filgrastim, G-CSF
Single s.c. dose of G-CSF (300 microg)
干预措施: Filgrastim, hrG-CSF (Drug)
结局指标
主要结局
CPC mobilization after a single G-CSF dose
时间窗: 0-24 hours
Circulating progenitor cell level will be assessed before and 24 hours after a single G-CSF dose in both diabetic and non diabetic patients. Change in CPC level will be indicative of bone marrow mobilization. Mobilization will be compared in diabetic versus non diabetic subjects.
次要结局
未报告次要终点
研究者
Angelo Avogaro
Professor of Endocrinology
University of Padova