NOVEL TREATMENT FOR CYSTINURIA AND STONES OF IMMOBILIZATION

该项目的总体目标是确定新的硫醇 化合物（Rimatil）将比Thiola更有效和安全， 控制胱氨酸尿症和胱氨酸结石形成，并确定是否 一种新的二膦酸盐（阿仑膦酸盐）可能会防止结石形成， 长时间的固定。 将描述剂量反应关系 为了显示Rimatil比Thiola更有效降低 胱氨酸排泄。 3年。Rimatil和Thiola之间的随机试验 将在胱氨酸尿患者中进行，调整每种药物的剂量 以实现胱氨酸排泄的最佳控制（250-400 mg/天）。 终点将是药物剂量和副作用特征， 预期Rimatil组需要更低的剂量， 使用安全。采用卧床模型， 固定（或太空飞行）已被证明是由于增加 骨丢失引起的钙和磷酸盐的肾排泄。阿仑膦酸钠可能 防止尿钙和磷酸盐的上升（以及尿中的钙和磷酸盐）。 结石形成钙盐的饱和）。 该方案将在正常受试者中进行测试， 在达拉斯的卧床休息和那些参加了一项为期17周的卧床休息研究， 休斯顿这些研究具有生物医学的重要性，因为它们可以使 改善胱氨酸尿症的治疗，并导致一种 太空旅行中结石形成有效对策 固定状态。

The overall goal of this project is to determine whether a new thiol compound (Rimatil) would be more effective and safer than Thiola in controlling cystinuria and cystine stone formations, and to ascertain if a new diphosphonate (alendronate) might prevent stone formation from prolonged immobilization. A dose response relation will be characterized in order to show that Rimatil is more effective than Thiola in lowering cystine excretion. A 3 yr. randomized trial between Rimatil and Thiola will be conducted in cystinuric patients, with the dose of each adjusted to achieve an optimum control of cystine excretion (250-400 mg/day). Endpoints will be drug dosage and side effect profile, with the expectation that Rimatil group would require a lower dose and improved safety of usage. Using bedrest model, stone formation during prolonged immobilization (or space flight) has been shown to be due to increased renal excretion of calcium and phosphate from bone loss. Alendronate might prevent the rise in urinary calcium and phosphate (and in urinary saturation of stone-forming calcium salts) by inhibiting bone resorption. This scheme will be tested in normal subjects undergoing 3 weeks of bedrest at Dallas and those participating in a 17-week bedrest study at Houston. These studies have biomedical importance, since they may allow improved treatment of cystinuria, and lead to the development of an effective countermeasure for stone-formation during space travel and other immobilization states.