EFFECT OF ORAL MAGNESIUM PIDOLATE IN PATIENTS WITH HEMOGLOBIN SC DISEASE

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。这是一项随机、双盲、安慰剂对照的II期研究，交叉设计如下所示。在达到资格标准后，患者将被随机分配到研究药物(mg匹多酯或安慰剂)24周，然后是8周的冲洗期。在洗涤期结束后，每个患者将再接受24周的研究药物治疗。这项研究将在波士顿的德克萨斯儿童癌症中心、血液学服务和儿童医院进行。预计将在四年内招募20名患者，每个患者进行16个月的研究。将需要21次诊所就诊，每次就诊时要进行间歇性病史和体检(包括对所有月经后女性的尿孕试验，因为镁对孕妇和胎儿的影响有问题)，以监测和评估任何毒性。在整个研究过程中，将进行血液测试，以监测血液学、血清化学、肾功能和肝功能。在8次访问中，还将抽取血液用于膜转运研究和体内外形态镰刀状的评估，在4次访问中，还将抽取血液用于血清储存。在这项研究中，每个患者在13次就诊中每次采集的血液总量为120毫升(24茶匙)-2-3毫升(半茶匙)，每次4次就诊为5毫升(1茶匙)，4次就诊为15毫升(3茶匙)。每次就诊4次将采集尿液进行尿检。患者(或他们的父母，如果合适)将被要求保留一份书面记录(以日记的形式)，记录所有疼痛发作或任何其他通知的变化。对研究药物有反应的患者将被允许继续使用研究药物治疗，直到研究结束。这项研究的药物将是一种液体，每天含有0.6MEQ毫克/公斤体重的匹多酚或等量的安慰剂，分成每天两次剂量。这个剂量略高于生理性镁补充剂(5毫克/公斤/天)，但低于镁缺乏治疗所用的剂量(&gt；10毫克/公斤/天)，大约相当于每天3米兰特双倍强度药片。镁(45克)将以预先混合的粉末的形式分发，其中含有库莱德热带冲压粉(9克)和蔗糖(67克)。每1/8茶匙含镁0.29克(23.7 mg mg 2)=1.97meq mg 2=1 mmol mg。这种粉末易溶于水，味道宜人。安慰剂将含有等量的蔗糖和热带喷雾粉以及45克乳糖。

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. This is a randomized, double-blind, placebo-controlled phase II study with cross-over design as shown below. After meeting eligibility criteria, patients will be randomly assigned to study medication (Mg pidolate or placebo) for 24 weeks, followed by a washout period of 8 weeks. After the washout period, each patient will receive a further 24 weeks of study medication. The study will be conducted at Texas Children's Cancer Center and Hematology Service and Children's Hospital, Boston. It is expected that 20 patients will be enrolled over four years, with each patient on study for 16 months. 21 clinic visits will be required, with interval history and physical examination (including a urine pregnancy tests for all post-menarchal females due to the questionable effects of magnesium on pregnant women and fetuses) at each clinic visit in order to monitor for and evaluate any toxicities. Blood tests will be taken throughout the study to monitor hematology, serum chemistry, renal function and liver function. At 8 visits, blood will also be drawn for membrane transport studies and assessment of morphologic sickling in vitro and in vivo, and at 4 visits, blood will also be drawn for serum storage. The total amount of blood collected per patient during this study is 120ml (24 teaspoons) - 2-3ml (half teaspoon) at each of 13 visits, 5ml (I teaspoon) at each of 4 visits and 15ml (3 teaspoons) on 4 visits. Urine will be collected on 4 visits for urinalysis. The patient (or their parent, if appropriate) will be asked to keep a written record (in the form of a diary) of all episodes of pain or any other changes that are notice. Patients who are responding to the study medication will be allowed to continue treatment with the study medication until the study is closed. The study medication will be a liquid containing either 0.6 meq Mg pidolate/kg body weight per day or an equivalent amount of placebo, divided into 2 daily doses. This dose is slightly higher than physiologic magnesium supplementation (5 mg/kg/day) but lower than the doses used for Mg deficiency treatment (>10 mg/kg/day), and is approximately equivalent to 3 Mylanta double strength tablets per day. The Mg pidolate (45 g) will be distributed as a pre-mixed powder containing KoolAid Tropical Punch powder (9 gm), and sucrose (67 gm). This breaks down to (per 1/8 teaspoon) Magnesium pidolate 0.29 gm (23.7 mg Mg 2+) = 1.97 meq Mg 2+ = 1 mmol Mg. The powder is easily dissolved in water and has a pleasant taste. The placebo will have the same amount of sucrose and Tropical Punch powder as well as 45 g of lactose.