PHASE II TRIAL OF DHEA IN CHRONIC RENAL FAILURE

我们已经观察到，在之前由GCRC支持的患者研究中 对于慢性肾功能衰竭，这种进展呈负相关 有脱氢表雄酮-S水平的患者；即水平相对较低的患者 这种荷尔蒙(对于他们的年龄和性别)进展迅速，而 水平相对较高的患者进展缓慢。在此基础上 我们已经建立了双盲、随机、交叉、剂量- 慢性肾脏病患者补充脱氢表雄酮的调整试验 失败了。在确定(通过顺序确定 肾小球滤过率)(GFR)表明进展正在发生，我们 随机将患者首先接受安慰剂或脱氢表雄酮，然后 相反，在两个相等的观察周期中，长度不同 2至6个月(取决于之前的进展速度)。血清 脱氢表雄酮-S的水平在前四周每周测量一次 周期，并向非盲人报告，由其调整剂量 脱氢表雄酮胶囊与安慰剂胶囊的比较以实现血清脱氢表雄酮-S 水平接近12微克/毫升(在接受脱氢表雄酮的人中)。到目前为止有8个 患者已经进入了这个方案。两名患者，一名非 胰岛素依赖型糖尿病和一名IgA肾病患者 在补充脱氢表雄酮的过程中表现出加速进展。一名患者 有胰岛素依赖型糖尿病和多囊肾 在补充脱氢表雄酮的过程中，疾病进展缓慢。我们的 未来的研究将仅限于后两种障碍。脱氢表雄酮 除此之外，毒性还没有被注意到。

We have observed, in previous GCRC-supported studies of patients with chronic renal failure, that progression in negatively correlated with serum level of DHEA-S; i.e., patients with relatively low levels of this hormone (for their age and gender) progress rapidly while patients with relatively high levels progress slowly. Based on this finding, we have instituted a double-blind, randomized, crossover, dose- adjustment trial of DHEA supplementation in patients with chronic renal failure. After establishing (by sequential determinations of glomerular filtration rate) (GFR) that progression is occurring, we randomize patients to receive either placebo or DHEA first, followed by the opposite, in two equal periods of observation, varying in length from 2 to 6 months (depending on the prior rate of progression). Serum levels of DHEA-S are measured weekly for the first four weeks of both periods, and reported to an unblinded individual, who adjusts the dosage of DHEA capsules vs. placebo capsules so as to achieve a serum DHEA-S level approximating 12 ug/ml (in those receiving DHEA). So far 8 patients have entered this protocol. Two patients, one with non- insulin-dependent diabetes mellitus and one with IgA nephropathy, have shown accelerated progression during DHEA supplementation. One patient with insulin-dependent diabetes mellitus and one with polycystic kidney disease have shown slowed progression during DHEA supplementation. Our future studies will be limited to these latter two disorders. DHEA toxicity has not been noted otherwise.