PILOT STUDY OF EFFICACY OF PROCYSTEINE IN TREATMENT OF HYPEROXALURIA

本研究的主要目的是确定OTZ（原半胱氨酸）短期静脉给药是否导致草酸盐尿排泄的临床相关减少。 如果达到了这一目的，就有必要进一步测试原半胱氨酸治疗原发性高尿酸血症的口服剂量。将入组2例受试者，并在马约GCRC或Bowman Gray医学院GCRC（温斯顿-塞勒姆，北卡罗来纳州）进行研究。入组的受试者将以非盲方式接受OTZ治疗，并在药物给药前后测量尿草酸盐以及血浆草酸盐、OTZ和半胱氨酸。 如果受试者表现出尿草酸盐排泄减少大于50 mg/24小时或>35 mg/gm肌酐基线，这在治疗这种疾病中被认为是临床显著的，则将提交单独的方案用于在盲法、随机化、交叉临床试验中研究OTZ或安慰剂。GCRC研究持续时间为12天。 这可能是一个12天的住宿或两个6天的住宿完成。 在整个研究期间，将保持膳食草酸盐、钙和蛋白质的恒定。OTZ已经在动物和人类中进行了研究，迄今为止在健康志愿者以及患有ARDS、败血症和HIV感染的患者中进行了人类研究。 迄今为止，在140多名艾滋病毒感染者中进行了最大规模的研究。 患者接受高达9000 mg/天的原半胱氨酸治疗6个月，总体而言，药物耐受性良好，具有良好的安全性。

The primary objective of this study is to determine if the short-term intravenous administration of OTZ (procysteine) results in a clinically relevant decrease in the urinary excretion of oxalate. If this objective is met, it will warrant further testing of oral doses of procysteine in the treatment of primary hyperoxaluria. Two subjects wil be enrolled and will be studied either at the Mayo GCRC or at the Bowman Gray School of Medicine GCRC (Winston-Salem, North Carolina). The subjects enrolled will receive OTZ in a nonblinded fashion with measurements of urine oxalate as well as plasma oxalate, OTZ, and cysteine before and after administration of the drug. If the subjects demonstrate a reduction in urine oxalate excretion of greater than 50 mg/24 hours or >35 mg/gm creatinine of baseline, which would be considered clinically significant in the treatment of this disorder, a separate protocol will be submitted for the study of OTZ or placebo in a blinded, randomized, crossover clinical trial. Duration of the study will be 12 days in the GCRC. This may be completed as a single 12 day stay or two 6 day stays. Constancy of dietary oxalate, calcium, and protein will be maintained throughout the study. OTZ has been studied in animals and humans with human studies thus far conducted in healthy volunteers as well as patients with ARDS, sepsis, and HIV infection. The largest study to date was conducted in over 140 patients with HIV infection. Patients received up to 9000 mg/day of procysteine for a six month period and, in general, the drug was well tolerated and had a favorable safety profile.