A Pilot Study of N-acetylcysteine in Patients With Sickle Cell Disease
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Bloodworks
- 入组人数
- 21
- 试验地点
- 1
- 主要终点
- Laboratory measures of VWF activity
研究概览
简要总结
Part 1: A pilot study in patients with homozygous S (HbSS) or hemoglobin S with beta zero thalassemia(HbS-βo thalassemia), with the aim of examining the effect of intravenous NAC treatment on plasma VWF parameters and measures of redox and RBC function.
Part 2: A pilot study in patients with sickle cell disease admitted to the hospital in vaso-occlusive crisis to determine the effects of NAC infusions on plasma VWF parameters and measures of redox and RBC function, and on measures of pain and hospital length of stay.
详细描述
Two primary processes dominate the complications associated with sickle cell disease (SCD): vasoocclusion and hemolysis. The plasma and vessel wall adhesive protein von Willebrand factor (VWF) is thought to be involved in both of these processes, so strategies aimed at reducing its secretion or reactivity, which could decrease complications in patients with SCD, are being tested.
Based on prior studies, N-acetylcysteine (NAC) treatment may decrease VWF activity in patients with SCD and may be a useful adjunctive treatment in this disorder.
Part 1 enrolls stable outpatients with homozygous S (HbSS) or hemoglobin S with beta zero thalassemia (HbS-βo thalassemia), with the aim of examining the effect of NAC treatment on VWF parameters, measures of oxidation and RBC fragments. Patients receive IV NAC first at 150 mg/kg over 8 hours and if tolerated, at a later date at 300 mg/kg over 8 hours in the University of Washington Clinical Research Center. Blood is collected for laboratory assessment. Subjects are later offered enrollment in an oral phase.
Part 2, patients with a history of vaso-occlusive crisis (VOC) are approached in the outpatient setting to discuss the study. When admitted for VOC, subjects receive NAC as an IV infusion75 mg/kg every 6 hours for up to 5 days. Blood for laboratory assays are collected each morning and pain assessment is performed prior to and following each NAC infusion.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age >= 18 years of age
- •Diagnosis of homozygous sickle cell (SS) or S-beta thalassemia with at least two episodes of vaso-occlusive crises (VOC) requiring narcotics in each of the past 2 years. For part 2 can include hemoglobin SC disease.
- •For females of reproductive age, use of contraception and negative pregnancy test
排除标准
- •An additional hematologic diagnosis
- •Hemoglobin (Hgb) < 7gm/dL for part 1, < 6 gm/dL for part
- •Asthma requiring medication
- •Liver function tests [alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (BilliT) > three times upper normal limit for Part
- •Chronic transfusion therapy, or transfusion within 2 months of enrollment. For part 2 anticipated need for simple or exchange transfusion during hospitalization.
- •VOC requiring narcotic therapy within the prior week or requiring hospitalization with discharge < 2 weeks prior to study enrollment for Part 1, for part 2 admission for VOC within 30 days.
- •Pregnancy or nursing
- •Receiving another investigational drug
- •Known allergy to NAC
- •Per subject's physician not medically stable enough to participate
- •Taking nitroglycerin, carbamazepine, or phosphodiesterase 5 (PDE5) inhibitors
- •Abnormal baseline coagulation tests (> 1.5 times normal limits)
- •Platelets <150,000/microliter for Part
- •For part 2, already enrolled in study twice.
研究组 & 干预措施
Oral N-acetylcysteine (NAC)
Eligible subjects who did not participate in Intravenous NAC or subjects who are at least 4 weeks after participation in Intravenous NAC, will be given Oral NAC at a dose of 2400mg daily, in two equally divided doses, for 4 weeks. Subjects will have blood drawn prior to beginning the phase and weekly for 4 weeks. At each visit interim medical events and adverse events will be collected.
干预措施: N-Acetylcysteine (Drug)
Intravenous N-acetylcysteine (NAC)
For part 1, Eligible subjects who did not participate in Oral NAC or subjects at least 4 weeks after oral NAC will receive IV NAC 150 mg/kg over 8 hours. At least four weeks after the first infusion, the subject will receive IV NAC 300 mg/kg over 8 hours.
For part 2, Eligible subjects with sickle cell disease and hospitalization for VOC within the past 2 years, who now present in VOC will be enrolled. Subjects will receive IV NAC 75 mg/kg over 1 hour every 6 hours for 5 days or discharge, whichever occurs earlier.
干预措施: N-Acetylcysteine (Drug)
结局指标
主要结局
Laboratory measures of VWF activity
时间窗: Part 1, Prior to during and following one day infusion or during oral administration; Part 2, daily during infusion and just following infusion completion
To determine if NAC, given intravenously as a one day infusion, orally as an outpatient or during hospitalization for VOC has an effect on VWF level or function.
次要结局
- Adverse events during and following NAC administration(Adverse events will be measured from time of consent to completion of study, with particular attention to times around and during administration.)
- Pain during VOC(Before and following each NAC infusion while hospitalized)
- Laboratory measures of red blood cell hemolysis and oxidation(Red blood cell (RBC) lab measures will be drawn prior to infusion, at the end of the infusion, 1 and 3 days following the end of the infusion, once a week during oral administration, and daily during hospitalization)
- Use of pain medications in morphine equivalents(Morphine equivalents for the hospitalization during which NAC was administered compared to past VOC admissions)
- Hospital length of stay (LOS)(Days of hospitalization during study compared to past hospitalizations for VOC)
研究者
Barbara A. Konkle, M.D.
Director, Clinical and Translational Research
Bloodworks