Phase I/II Study of Simvastatin (Zocor) Therapy in Sickle Cell Disease
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 42
- 试验地点
- 1
- 主要终点
- Change in Serum Creatine Kinase Levels
研究概览
简要总结
Recent clinical and experimental data indicate that statins have effects beyond cholesterol lowering that may be beneficial in sickle cell disease by protecting the vascular endothelium. Statins have been shown to attenuate endothelial dysfunction through their anti-inflammatory, anti-oxidant and anti-thrombotic properties. This phase I/II dose-escalating trial is designed to assess the safety and potential clinical efficacy of oral simvastatin (Zocor)in adolescents and adults with sickle cell disease (SCD).
详细描述
Although statins have been used extensively for their cholesterol-lowering effects, recent clinical and experimental data indicate that statins regulate yet other processes, many of which play a major role in sickle cell disease (SCD). Independent of their cholesterol-lowering effects, statins have been shown to prevent damage to blood vessels in several ways, through upregulation of endothelial nitric oxide (NO)and decreased inflammation. Numerous studies documenting the protective effects of statins, together with data showing the therapeutic role of NO in SCD, provide the basis for investigating the potential clinical benefit of simvastatin in SCD.
Data supporting the safety and tolerability of simvastatin in patients with SCD are now needed. For this phase I/II dose-escalation study of oral simvastatin in SCD, we propose the following specific aims:
- To obtain preliminary efficacy data on the effects of oral simvastatin on plasma biomarkers of endothelial injury in patients with SCD, and
- To assess the safety and tolerability of oral simvastatin in patients with SCD.
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
- 13 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Established diagnosis of sickle cell disease (HbSS, SC or Sβ-thalassemia)
- •Age greater than or equal to thirteen years
- •Weight greater than or equal to 35 kg
排除标准
- •Renal dysfunction (Serum Creatinine > 1.5 UNL)
- •Hepatic dysfunction (ALT > 2X UNL)
- •Pretreatment total cholesterol < 100 mg/dL or triglycerides < 30 mg/dL
- •Pretreatment baseline creatine kinase >1X UNL (215 U/L)
- •Pregnancy/lactation
- •RBC transfusion in the last 30 days
- •Vaso-Occlusive Event needing hospitalization in the past 30 days
- •Treatment with any statin drugs within the past 30 days
- •Treatment with drugs having known metabolic interactions with statin drugs (e.g. cytochrome P450 3A4 metabolism), including ketoconazole, itraconazole, fluconazole, erythromycin, clarithromycin, azithromycin, niacin (nicotinic acid), digoxin, coumadin, sildenafil or amiodarone within the past 30 days
- •Treatment (past or present) with amiodarone
- •Musculoskeletal disorder associated with an elevated creatine kinase level
- •Past or present history of substance abuse (alcohol, cocaine, amphetamines, heroin, PCP)
- •Allergy to statins
研究组 & 干预措施
Simvastatin, Dose Escalation
There are no arms in this study. Simvastatin will be given in a dose-escalating fashion to 3 sequential dosage groups (20 mg/day, 40 mg/day, 80 mg/day).
干预措施: Simvastatin (Drug)
结局指标
主要结局
Change in Serum Creatine Kinase Levels
时间窗: Baseline, 21 days
Change in serum creatine kinase (CK) levels after treatment with simvastatin
Change in Hemoglobin Level
时间窗: Baseline, 21 days
Change in plasma hemoglobin (Hb) level after treatment with simvastatin
Change in Total Cholesterol Level
时间窗: Baseline, 21 days
Change in serum total cholesterol level after treatment with simvastatin
Change in Serum Alanine Transaminase (ALT) Levels
时间窗: Baseline, 21 days
Change in serum alanine transaminase (ALT) after treatment with simvastatin
Change in Serum Creatinine Levels
时间窗: Baseline, 21 days
Change in serum creatinine (Cr) levels after treatment with simvastatin
次要结局
未报告次要终点
研究者
Carolyn Hoppe
Associate Hematologist
UCSF Benioff Children's Hospital Oakland