EFFECT OF ORAL MAGNESIUM PIDOLATE IN PATIENTS WITH HEMOGLOBIN SC DISEASE

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。这是一项随机、双盲、安慰剂对照的II期研究，交叉设计如下图。在符合资格标准后，患者将被随机分配到研究药物（Mg pidolate或安慰剂）24周，然后是8周的洗脱期。洗脱期结束后，每位患者将再接受24周的研究用药。这项研究将在德克萨斯儿童癌症中心、血液学服务中心和波士顿儿童医院进行。预计将在4年内招募20名患者，每位患者进行16个月的研究。每次就诊需进行21次门诊检查，并定期进行病史和体格检查（包括对所有月经后女性进行尿液妊娠试验，因为镁对孕妇和胎儿的影响值得怀疑），以便监测和评估任何毒性。在整个研究过程中，将进行血液检查，以监测血液学、血清化学、肾功能和肝功能。在8次就诊时，还将抽血用于膜转运研究和体外和体内形态镰状细胞的评估，在4次就诊时，还将抽血用于血清储存。在本研究中，每位患者采集的血液总量为120ml（24茶匙）- 13次每次采集2-3ml（半茶匙），4次每次采集5ml（1茶匙），4次采集15ml（3茶匙）。将于4次访视中收集尿液作分析。将要求患者（或其父母，如果合适）保留所有疼痛发作或注意到的任何其他变化的书面记录（日记形式）。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。研究药物将是一种液体，每天含有0.6 meq Mg /kg体重的pidolate或等量的安慰剂，分为2次每日剂量。该剂量略高于生理性镁补充（5mg /kg/天），但低于镁缺乏症治疗的剂量（10mg /kg/天），大约相当于每天3片mylananta双强度片。Mg pidolate（45克）将作为含有KoolAid Tropical Punch粉（9克）和蔗糖（67克）的预混合粉末分发。这分解为（每1/8茶匙）碘酸镁0.29克（23.7毫克mg 2+） = 1.97毫克mg 2+ = 1毫摩尔mg。这种粉末易溶于水，味道很好。安慰剂将含有相同数量的蔗糖和热带潘趣粉以及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.