A Phase 1 Dose Escalation Study of Continuous Intravenous L-citrulline During Sickle Cell Pain Crisis or Acute Chest Syndrome
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 4
- 试验地点
- 1
- 主要终点
- Number of Participants With Adverse Events
研究概览
简要总结
Sickle cell disease is a genetic red blood cell disorder characterized by vaso-occlusion from sickling of red blood cells, that can lead to pain or organ complications such as acute chest syndrome. Sickle cell disease is associated with low amounts of nitric oxide, a compound important for dilating the blood vessel wall. Citrulline is a substance that is known to increase nitric oxide. The goal of this Phase I study are to find the highest safe dose of continuous IV citrulline that can be given to individuals with sickle cell disease experiencing a sickle cell pain crisis or acute chest syndrome without causing severe side effects.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 6 Years 至 50 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Sickle cell disease genotypes (HbSS, HbS/β0-thalassemia, HbS/β+-thalassemia, HbSC)
- •Ages 6 to 50 years old
- •Patients with sickle cell disease aged 6 to 50 years old Presence of sickle cell pain crisis defined by the presence of pain requiring hospitalization and parental opioid therapy
- •Presence of acute chest syndrome defined by the presence of a new CXR infiltrate and any one of the following respiratory symptoms of fever, shortness of breath, wheezing, chest pain, cough or new onset hypoxia.
排除标准
- •Presence of any other complication related to sickle cell disease requiring hospitalization such as splenic sequestration, hepatic sequestration, stroke, avascular necrosis of the hip/shoulder, acute priapism, etc.
- •Severe anemia (hemoglobin < 5g/dL)
- •History of red blood cell transfusion within the last 30 days
- •Systemic steroid therapy within the last 48 hours
- •Pregnant (as confirmed by a negative urine pregnancy test) or lactating female
- •Alanine/aspartate transferase >2x upper limit of normal laboratory range for age.
- •Subject has the following serum creatinine:
- •Age 6 to 13 years > 0.9 mg/dL
- •Age 14-17 years 1.0 mg/dL
- •Age 18 years >1.5mg/dL
- •Patients with an inability to give consent will be excluded
研究组 & 干预措施
Intravenous citrulline
Intravenous citrulline at a bolus dose over 5 minutes and then a continuous rate for the next 23 hours.
干预措施: Intravenous citrulline (Drug)
结局指标
主要结局
Number of Participants With Adverse Events
时间窗: 30 days
The number and severity of adverse event will be determined according to the NCI Common Terminology Criteria for Adverse Events (CTCAE)
Plasma Citrulline Level
时间窗: Plasma citrulline levels will be evaluated at the following time points: trough level, 10 minutes (peak level), 30 minutes, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 24 hours and 48 hours, to evaluate the pharmacokinetic profile
次要结局
未报告次要终点
研究者
Suvankar Majumdar
Associate Professor
University of Mississippi Medical Center