Sargramostim to Reverse Myeloid Dendritic Cell Deficiency
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 4
- 试验地点
- 1
- 主要终点
- Change in peripheral blood mDC levels
研究概览
简要总结
The study will determine whether administration of sargramostim will improve myeloid dendritic cell deficiency in various study groups, including healthy subjects and patients with chronic kidney disease, including those with kidney transplants.
详细描述
The overall objective of this project is to study the ability of sargramostim to enhance mDC level and function, including subsequent stimulation of T cell responses, in various human subjects with demonstrated myeloid dendritic cell (mDC) and T cell deficiency.
Single center nonrandomized trial with an interrupted time series design involving measures on blood samples from three separate populations before and after administration of sargramostim.
The objective is to determine the safety and dose response of sargramostim administration in healthy participants and in patients with chronic kidney disease (CKD) and kidney transplants.
Additionally to determine whether reversal of mDC/T cell deficiency by sargramostim results in augmented T cell responses in these three groups.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
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
- •Age >18 years < 80 years
- •Absence of acute or chronic medical condition and taking no prescription medications (Project I)
- •Stable native or transplant kidney function (Project II/III)
排除标准
- •Age < 18 or > 80 years
- •History of non-adherence to prescribed medications (Projects II and III)
- •Active drug or heavy alcohol use (defined as > 4 drinks/day)
- •Pregnancy or breast feeding
- •Active infection (bacterial or viral) or clinically significant infections within the past three months (e.g. those requiring hospitalization, or as judged by the PI, except for CMV viremia in Project III)
- •Active malignancy (with the exception of excised non-metastatic basal cell carcinoma or squamous cell carcinoma of the skin, or adequately treated pre-invasive cervical cancer in situ)
- •Unstable cardiovascular status (angina, arrhythmias, congestive heart failure (CHF) etc...)
- •History of liver disease (as defined by a diagnosis of uncompensated cirrhosis)
- •History of lung disease (including moderate-severe Chronic Obstructive Pulmonary Disease (COPD), interstitial lung disease, or asthma)
- •Known hypersensitivity to yeast-derived products
- •Hemoglobin < 10 g/dL and hematocrit < 30%.
- •Abnormal white blood cell count (WBC) count at baseline (< 3 or > 12 x 103 cells/mm3, except Project III)
- •Treatment with WBC growth factors (G-CSF or GM-CSF) or immunosuppressive medications (tacrolimus, cyclosporine, mycophenolate, azathioprine, corticosteroids, chlorambucil, cyclophosphamide) within 4 weeks of study (erythropoiesis-stimulating agents will be allowed for Project II and immunosuppression for Project III)
- •Treatment with lithium within 4 weeks of study
- •History of arterial or venous thrombosis
研究组 & 干预措施
Project I: Healthy participants
5 healthy participants will be used to optimize the dosage and timing of sargramostim administration with regard to the primary and secondary outcomes. Blood samples will be drawn and analyzed for mDC levels.
干预措施: Sargramostim (Drug)
Project I: Healthy participants
5 healthy participants will be used to optimize the dosage and timing of sargramostim administration with regard to the primary and secondary outcomes. Blood samples will be drawn and analyzed for mDC levels.
干预措施: Blood samples (Biological)
Project II: Patients with CKD stage IV/V
5 Patients with CKD stage IV/V who are cytomegalovirus (CMV) seropositive with mean blood mDC levels <1.0x104/mL will receive sargramostim treatment once all 5 healthy participants have completed treatment and the data have been analyzed to guide subsequent dosing. Blood samples will be drawn and analyzed for mDC levels.
干预措施: Sargramostim (Drug)
Project II: Patients with CKD stage IV/V
5 Patients with CKD stage IV/V who are cytomegalovirus (CMV) seropositive with mean blood mDC levels <1.0x104/mL will receive sargramostim treatment once all 5 healthy participants have completed treatment and the data have been analyzed to guide subsequent dosing. Blood samples will be drawn and analyzed for mDC levels.
干预措施: Blood samples (Biological)
Project III: kidney transplant patients
5 Kidney transplant recipients who are CMV seropositive with neutropenia (defined as absolute neutrophil count <1.0 x103/mm3) and/or CMV viremia will receive sargramostim treatment once all 5 Project I participants have completed treatment and the data have been analyzed to guide subsequent dosing. Blood samples will be drawn and analyzed for mDC levels.
干预措施: Sargramostim (Drug)
Project III: kidney transplant patients
5 Kidney transplant recipients who are CMV seropositive with neutropenia (defined as absolute neutrophil count <1.0 x103/mm3) and/or CMV viremia will receive sargramostim treatment once all 5 Project I participants have completed treatment and the data have been analyzed to guide subsequent dosing. Blood samples will be drawn and analyzed for mDC levels.
干预措施: Blood samples (Biological)
结局指标
主要结局
Change in peripheral blood mDC levels
时间窗: Baseline to 2 weeks
mDC levels to \>2.0 x104 mDCs/mL, with the target level defined as levels at or above upper quartile values in healthy controls
次要结局
- Proportion of patients with adverse events during the intervention.(Baseline to 2 weeks)
- Increase in T cell levels, mDC Interleukin (IL)-12 production, and interferon-gamma (IFN-y) production in QuantiFERON-CMV and QuantiFERON-Monitor assays after the intervention.(Baseline to 2 weeks)