TRIAL OF BUTYRATE IN BETA GLOBIN DISORDERS

丁酸盐治疗β珠蛋白疾病的试验

• 批准号: 7379532
• 负责人: SUSAN Park PERRINE
• 金额: $ 0.15万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-12-01 至 2006-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7379532
• 关键词: TRIAL; BUTYRATE; BETA; GLOBIN; DISORDERS

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The experimental design is to administer different doses of Butyrate on an intra-patient, dose escalation schedule and to analyze Hb F production (through measurement of F-cells, F-reticulocytes, globin chain synthesis ratios, Hb F, globin mRNA), and hematologic tests, to determine an effective regimen for the individual patient. The latter tests include CBCs, differentials, reticulocyte counts, plasma free hemoglobin, proportions of irreversibly sickled cells, and globin chain electrophoresis. Chemistry panels and urinalyses will be followed to monitor for side effects. Drug levels are measured in plasma and urine. Optimal globin chain ratios are expected at 24-48 hours after dose, but have persisted for 7-10 days in some thalassemia patients. After a correction or a significant improvement in globin chain ratio or fetal globin synthesis is detected, that dose will be continued and blood drawings will be decreased in frequency. If biochemical responses are not detected, hematologic improvement can not be expected to follow. Accordingly, patients will not be continued on study, if stimulation of Hb F by at least one parameter is not detected after a maximal administered dose of 2000 mg/kg. Infusion rates will be adjusted to deliver the desired total dose at a rate tailored to avoid side effects such as nausea and headache and suppression of hemoglobin synthesis thought to be induced by excessively high plasma levels of the drug. Doses will be infused over 4 to 18 hours, at a rate not to exceed 85 mg/kg/hour. Drug will be given from 1 to 4 days per week, followed by at least 5-14 days without drug, while the patient's blood is sampled and tested. Intervals between drug treatments may be extended beyond 14 days, in order to determine how long the drug effect lasts and how often therapy is really needed once Hb F inverses. After an effective dose for a given patient is identified at the biochemical level, and a rise in total hemoglobin or a decrease in post-transfusion hemoglobin nadir is observed, the frequency of blood testing will be decreased to 4 times/ month.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子弹和调查员（PI）可能已经从其他NIH来源获得了主要资金，因此可以在其他清晰的条目中代表。列出的机构适用于该中心，这不一定是调查员的机构。实验设计是在患者内，剂量升级时间表上施用不同剂量的丁酸酯，并分析HB F的生产（通过测量F细胞，F-续线细胞，Globin链合成率，HB F，Globin mRNA）和血液学测试，以确定对个体患者的有效治疗方案。后者的测试包括CBC，差异，网状细胞计数，无血浆血红蛋白，不可逆疾病的细胞比例和球蛋白链电泳。化学面板和尿液线将被遵循以监测副作用。药物水平在血浆和尿液中测量。预计在剂量后24-48小时内，最佳球蛋白链比率是最佳的，但在一些thalassybia患者中持续了7-10天。在检测到球蛋白链比率或胎儿球蛋白合成的校正或显着改善后，将继续剂量，频率将降低血液图。 如果未检测到生化反应，则不能预期血液学改善。因此，如果在2000 mg/kg的最大剂量后未检测到HB F的刺激，则不会继续进行研究。 输注率将进行调整，以量身定制的速率输送所需的总剂量，以避免副作用，例如恶心，头痛以及抑制血红蛋白合成的抑制作用，被认为是由过高的血浆药物水平诱导的。剂量将在4至18小时内注入，速度不超过85 mg/kg/小时。药物将每周1至4天服用，然后至少5-14天没有药物，而患者的血液进行采样和测试。药物治疗之间的间隔可能会延长14天以上，以确定药物作用持续多长时间，以及一旦HB F逆，真正需要进行治疗的频率。在在生化水平上确定了给定患者的有效剂量后，总血红蛋白升高或观察到转移后血红蛋白NADIR的降低，血液检查的频率将降低到每月4次。