PULSE LOADED IV CLOMIPRAMINE IN UNRESPONSIVE OCD

强迫症（OCD）是美国第四大最常见的精神障碍，经常致残。 20%到40%的强迫症患者对口服药物的反应不令人满意，需要进行8到10周的试验来确定给定的药物是否对患者有效。 这项研究的广泛，长期的目标是调查这些患者的新治疗的有效性，安全性和快速性。 我们提出了一个2个网站，随机，双盲对照试验，在76例治疗无反应的DSM-IV强迫症患者比较脉冲加载静脉氯丙咪嗪（CMI），（第1天，150毫克;第2天，200毫克;第3-5天，零）脉冲加载口服CMI（在相同的剂量），然后口服CMI治疗12周。 我们的主要假设是：1。双盲静脉内脉冲加载的CMI将在第6天之前在对大于或等于2个先前抗OCD药物试验无反应的OCD患者中产生临床上有意义的改善; 2.这种改善将显著超过由口服脉冲加载的CMI产生的改善;以及3.在12周的开放标签口服CMI维持试验结束时，静脉脉冲负荷患者比口服脉冲负荷患者经历了更大的改善。 我们的双盲初步研究结果与这些假设一致。 基于保守效应量0.7的把握度计算表明，76例患者将提供80%的把握度来检验p ≤ 0.05的主要假设。 我们还将探讨是否：1。第6天和第12周的结果与CMI及其代谢物的血浆水平相关;以及，2.可以从基线临床信息预测结果。（在整个修订后的资助申请中，除了新的介绍是普通字体外，修订都用粗体字表示）。

Obsessive-compulsive disorder (OCD) is the 4th most common mental disorder in the U.S. and is frequently disabling. From 20 percent to 40 percent of OCD patients do not respond satisfactorily to oral medications and an 8- to 10-week trial is needed to determine whether a given drug is effective for the patient. This study's broad, long-term objective is to investigate the efficacy, safety and rapidity of effect of a new treatment for these patients. We propose a 2-site, randomized, double-blind controlled trial in 76 patients with treatment-unresponsive DSM-IV OCD comparing pulse loaded intravenous clomipramine (CMI), (day 1, 150 mg; day 2, 200 mg; days 3-5, zero) to pulse loaded oral CMI (in identical doses) followed by 12 weeks of oral CMI treatment. Our primary Hypotheses are: 1. double-blind intravenous pulse loaded CMI will produce by day 6 a clinically meaningful improvement in OCD patients unresponsive to greater than or equal to 2 prior anti-OCD drug trials; 2. this improvement will significantly exceed that produced by oral pulse loaded CMI; and, 3. intravenous pulse loading patients will have experienced greater improvement by the end of a 12-week open-label oral CMI maintenance trial than oral pulse loading patients. Results of our double-blind Preliminary Study are consistent with these hypotheses. Power calculations based on a conservative effect size of 0.7 indicate that 76 patients would provide 80 percent power to test the Primary Hypotheses at p less than or equal to 0.05. We will also explore whether: 1. day 6 and week 12 outcomes are related to plasma levels Of CMI and its metabolites; and, 2. outcome can be predicted from baseline clinical information. (Throughout this revised grant application, revisions are indicated by bold type face, except that the new Introduction is in ordinary typeface).