EFFECT OF ORAL MAGNESIUM PIDOLATE IN PATIENTS WITH HEMOGLOBIN SC DISEASE

口服吡酮酸镁对血红蛋白 SC 疾病患者的影响

• 批准号: 7374937
• 负责人: BRIGITTA U MUELLER
• 金额: $ 0.4万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 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/7374937
• 关键词: EFFECT; ORAL; MAGNESIUM; PIDOLATE; PATIENTS

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.

该子项目是利用 NIH/NCRR 资助的中心拨款提供的资源的众多研究子项目之一。子项目和研究者 (PI) 可能已从另一个 NIH 来源获得主要资金，因此可以在其他 CRISP 条目中得到体现。列出的机构是中心的机构，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，采用交叉设计，如下所示。符合资格标准后，患者将被随机分配接受研究药物（吡酮酸镁或安慰剂）治疗 24 周，然后是 8 周的清除期。清除期结束后，每位患者将再接受 24 周的研究药物治疗。该研究将在德克萨斯儿童癌症中心以及波士顿血液服务和儿童医院进行。预计将在四年内招募 20 名患者，每位患者接受 16 个月的研究。需要 21 次就诊，每次就诊时都要进行间隔病史和体格检查（包括对所有初潮后女性进行尿妊娠测试，因为镁对孕妇和胎儿的影响值得怀疑），以监测和评估任何毒性。在整个研究过程中将进行血液检测，以监测血液学、血清化学、肾功能和肝功能。在 8 次就诊时，还将抽取血液进行膜转运研究以及体外和体内镰状细胞形态评估，在 4 次就诊时，还将抽取血液用于血清储存。本研究期间每位患者采集的血液总量为 120 毫升（24 茶匙） - 13 次就诊每次 2-3 毫升（半茶匙），4 次就诊每次 5 毫升（1 茶匙），4 次就诊每次 15 毫升（3 茶匙）。将在 4 次就诊时收集尿液进行尿液分析。将要求患者（或其父母，如果适用）保留所有疼痛发作或注意到的任何其他变化的书面记录（以日记的形式）。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，每天每公斤体重含有 0.6 meq 吡酮酸镁或等量的安慰剂，分为 2 次每日剂量。该剂量略高于生理性镁补充剂（5 mg/kg/天），但低于镁缺乏治疗的剂量（>10 mg/kg/天），大约相当于每天 3 片 Mylanta 双倍强度片剂。吡酮酸镁（45 克）将以包含 KoolAid 热带潘趣粉（9 克）和蔗糖（67 克）的预混合粉末形式分发。这分解为（每 1/8 茶匙）吡酮酸镁 0.29 gm（23.7 mg Mg 2+）= 1.97 meq Mg 2+ = 1 mmol Mg。该粉末易溶于水，味道宜人。安慰剂含有等量的蔗糖和热带宾治粉以及 45 克乳糖。