EFFECTS OF VPA 985 AND PLACEBO IN TREATMENT OF HYPONATREMIA

本研究的目的是确定VPA-985的剂量，VPA-985是一种选择性的加压素-2受体非肽拮抗剂，可以安全有效地提高各种原因的低钠血症患者的血钠水平。次要目标是比较门诊和住院患者的疗效，并确定纠正低钠血症是否能改善认知功能或其他临床益处的衡量标准。该设计为随机、双盲、平行组、安慰剂对照、多中心、住院和门诊研究。受试者年龄在18-80岁之间，患有因肝功能衰竭或SIADH引起的慢性低钠血症。研究前筛查后，他们将进入GCRC，并随机分配接受安慰剂或三剂VPA-985中的一剂，每天两次，连续七天。将限制液体摄入，并每天测定血钠、体重、尿量、生命体征和身体状况。治疗前后分别测定加压素等激素水平。如果临床表明，患者将在相同的治疗下出院，并在门诊随访两周。然后停止治疗，并进行最后的治疗后检查。认知功能测试将在住院和门诊阶段前后进行。除血钠外的所有测试都将由中心实验室进行或评分，结果将由惠氏-艾尔斯特公司分析。

The objective of this study is to determine the doses of VPA-985, a selective non-peptide antagonist of vasopressin-2 receptors, that safely and efficaciously increase serum sodium in patients with hyponatremia of diverse etiologies. Secondary objectives are to compare efficacy in an outpatient and inpatient setting and to determine if correction of the hyponatremia improves congnitive function or other measures of clinical benefit. The design is a randomized, double-blind, parallel group, placebo controlled, multi-center, inpatient and outpatient study. The subjects will be patients, age 18-80, with chronic hyponatremia due to liver failure or SIADH. After pre-study screening, they will be admitted to the GCRC and randomly assigned to receive placebo or one of three doses of the VPA-985 twice daily for seven days. Fluid intake will be restricted and serum sodium, body weight, urine output, vital signs and physical condition will be determined daily. Vasopressin and other hormones will be measured before and after the treatment. If clinically indicated, the patient will be discharged on the same treatment and followed in the outpatient clinic for two weeks. The treatment then will be stopped and the final post-treatment examination given. Cognitive function tests will be performed before and after the inpatient and oupatient phase. All tests except plasma sodium will be performed or scored by a central laboratory and the results will be analyzed by Wyeth-Ayerst.