PHASE III STUDY OF DOSE REGIMEN IN INITIAL NEUROLOGICAL WILSON'S DISEASE

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。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。列出的机构是 中心，不一定是研究者的机构。 我们过去的研究已经导致FDA批准锌用于威尔逊病的维持治疗。 锌现在可以取代毒性更大的青霉胺和曲恩汀。 锌对于治疗威尔逊病患者来说作用太慢，当他们首次出现急性铜中毒疾病时。 这些患者可能是急性脑损伤或肝损伤。 对于大脑（神经）发育的患者，我们沿着在开发一种新的药物，四硫代钼酸盐（TM），这是安全的，快速起效，有效。 然而，在当前剂量方案下，约12%的患者出现铜缺乏症症状（贫血、白细胞减少症），12%的患者出现转氨酶轻度升高。 这两种轻微的副作用都很容易通过减少TM剂量而逆转。 我们开发了这种双盲方案来测试一种新的剂量方案，该方案在较长的时间内给予较低剂量的TM，希望消除这些副作用，同时保持治疗效果。 我们将纳入所有患者（包括儿童），包括男性和女性，本研究中的所有种族。 他们将被随机分配标准TM方案或改良TM剂量方案。 所有患者也将获得锌。 患者将在密歇根大学医院的综合临床研究中心接受约6周的治疗，然后在家中接受另外10周的药物治疗。 将在家中每两周抽血一次，以进行持续评估。 治疗16周后，患者将返回UM进行随访。 接受传统TM剂量的患者将在TM治疗8周后继续接受锌维持治疗。 他们将接受TM安慰剂和锌，直到第16周。 接受新TM方案治疗的患者将在TM治疗16周后转为锌维持治疗。 如果本研究显示新的TM剂量方案是此类患者的一种上级治疗，则将降低过度治疗和转氨酶升高的发生率，同时保留患者的神经功能。'

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. Our past research has led to the development of an FDA approval of zinc for maintenance therapy of Wilson's disease. Zinc can now replace penicillamine and trientine, which have much more toxicity. Zinc is too slow acting for treating Wilson's disease patients when they first present with acute copper toxicity illness. These patients may be acutely ill from brain damage or liver damage. For the patients presenting with brain (neurologic) development, we are well along on developing a new drug, tetrathiomolybdate (TM), which is safe, fast-acting, and effective. However, approximately 12% of patients develop symptoms of copper deficiency (anemia, leukopenia), and 12% of patients develop mild elevations in transaminase enzymes under the current dose regimen. Both of these minor side effects are readily reversible by reducing the TM dose. We have developed this double-blind protocol to test a new dose regimen, which gives a lower dose of TM over a longer period of time than the standard regimen, in the hope of eliminating these side effects while preserving the efficacy of the treatment. We will include all patients (including children), both males and females, all ethnic groups in this study. They will be randomly assigned either the standard TM regimen or the modified TM dose regimen. All patients will receive zinc as well. Patients will be in the General Clinical Research Center of University of Michigan Hospital for about 6 weeks, then receive the drugs at home for another 10 weeks. Blood will be drawn every two weeks at home for continuing evaluation. After 16 weeks of therapy, patients will return to UM for a follow-up visit. Patients receiving the traditional TM dose will be kept on zinc maintenance therapy after 8 weeks of TM. They will receive a TM-placebo with the zinc until week 16. Patients on the new TM regimen will be transitioned to zinc maintenance therapy after 16 weeks of TM treatment. If this study shows the new TM dose regimen to be a superior treatment for this kind of patient, it will decrease the incidence of overtreatment and transaminase enzyme elevations, while preserving the neurologic function of patients.'