EFFECT OF ORAL MAGNESIUM PIDOLATE IN PATIENTS WITH HEMOGLOBIN SC DISEASE

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。子项目和研究者（PI）可能从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。所列机构为中心机构，不一定为研究者机构。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。在满足合格性标准后，患者将被随机分配至研究药物（匹多乐镁或安慰剂）治疗24周，随后是8周的洗脱期。洗脱期后，每例患者将再接受24周的研究药物治疗。该研究将在德克萨斯州儿童癌症中心和波士顿血液学服务和儿童医院进行。预计将在4年内入组20例患者，每例患者参与研究16个月。需要21次门诊访视，每次门诊访视时进行间隔病史和体格检查（包括所有月经后女性的尿妊娠试验，因为镁对孕妇和胎儿的影响值得怀疑），以监测和评价任何毒性。在整个研究期间将进行血液检查，以监测血液学、血清生化、肾功能和肝功能。在8次访视时，还将抽取血液用于膜转运研究和体外和体内镰状化形态评估，在4次访视时，还将抽取血液用于血清储存。本研究期间每例患者采集的血液总量为120 ml（24茶匙）-13次访视中每次采集2- 3 ml（半茶匙），4次访视中每次采集5 ml（1茶匙），4次访视中每次采集15 ml（3茶匙）。将在4次访视时采集尿液进行尿分析。将要求患者（或其父母，如适用）对所有疼痛发作或任何其他注意到的变化进行书面记录（以日记的形式）。允许对研究药物有反应的患者继续接受研究药物治疗，直至研究关闭。研究药物将是一种含有0.6 meq Mg Pidolate/kg体重/天或等量安慰剂的液体，分为2次每日剂量。该剂量略高于生理镁补充剂（5 mg/kg/天），但低于镁缺乏治疗所用的剂量（>10 mg/kg/天），约相当于每天3片Mylanta双倍强度片剂。将吡哆酸镁（45 g）作为含有KoolAid Tropical Punch粉末（9 g）和蔗糖（67 g）的预混粉末进行分配。这分解为（每1/8茶匙）吡啶酸镁0.29 gm（23.7 mg Mg 2+）= 1.97 meq Mg 2+ = 1 mmol Mg。这种粉末很容易溶于水，味道很好。安慰剂将含有相同量的蔗糖和Tropical Punch粉末以及45 g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.