Dose Timing of D-cycloserine to Augment CBT for Social Anxiety Disorder

D-环丝氨酸增强 CBT 治疗社交焦虑症的剂量时机

• 批准号: 9124959
• 负责人: MARK H POLLACK
• 金额: $ 23.25万
• 依托单位: RUSH UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-15 至 2018-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9124959
• 关键词: Academic Medical Centers; Acute; Address; Agonist; Algorithms; Anxiety Disorders; Basic Science; Boston; Characteristics; Clinical; Clinical Data; Clinical Research; Clinical Trials; Contracts; Cycloserine; Development; Doctor of Medicine; Doctor of Philosophy; Dose; Employee Strikes; Enrollment; Exposure to; Extinction (Psychology); Fright; Future; Glutamate Agonist; Goals; Grant; Health; Hour; Human; Intervention; Learning; Left; Link; Measures; Mental disorders; N-Methylaspartate; Nootropic Agents; Outcome; Patients; Personality Traits; Pharmaceutical Preparations; Pilot Projects; Placebos; Protocols documentation; Psyche structure; Psychopharmacology; Public Health; Publishing; Randomized; Research; Research Personnel; Safety; Severities; Site; Social Anxiety Disorder; Supervision; Testing; Texas; Therapeutic; Time; Training; Translational Research; Universities; arm; austin; base; clinical practice; cost effectiveness; efficacy testing; experience; follow-up; innovation; neural circuit; personalized medicine; pre-clinical; primary outcome; quality assurance; response; social anxiety; success; therapy outcome

DESCRIPTION (provided by applicant): This application is in response to PAR-12-071: Collaborative R34s for Pilot Studies of Innovative Treatments in Mental Disorders (Collaborative R34). D-cycloserine (DCS) is a partial N-methyl-D-aspartate glutamate agonist that has been shown to enhance exposure therapies for anxiety disorders. This approach is grounded in recent research advances in understanding the neural circuitry underlying fear extinction and is based upon one of the striking successes of translational research. All human clinical studies to date have administered DCS at least 1 hour prior to the exposure sessions. This dose-timing strategy limits the clinical utility of this highly promising augmentation strategy, especially sine accumulating research suggest that the efficacy of DCS for enhancing exposure therapy outcomes may depend on the success of exposure sessions. Pre-clinical and initial clinical data suggest that the DCS exposure-augmentation effect can also be obtained when DCS is administered immediately after an extinction trial when it follows successful exposure sessions. The proposed study builds upon this extant research by testing the efficacy of tailored post-session DCS administration (i.e., only following successful exposure sessions) for augmenting exposure therapy. In order to maintain high internal validity in this R34 study, we will enroll patients with social anxiety disorder (SAD) in a previously validated 5-session CBT protocol and randomize them to: (1) tailored post-session DCS administration; (2) pre-session DCS administration; (3) placebo administration; or (4) non-tailored post-session DCS administration. The primary outcomes will be short- and long-term improvements in social anxiety severity: We expect that the tailored post-session DCS administration condition will outperform the pre-session DCS administration, placebo administration, and non-tailored post-session DCS administration conditions, respectively, at posttreatment, 1-month and 3-month follow-up. In addition, we will explore potential moderators of the efficacy of tailored post-session DCS administration for augmenting exposure therapy. This application is the logical next step in the study of DCS. It provides an important innovative move toward the realization of personalized medicine by providing the first step in the eventual development of an algorithm for administering DCS in CBT with the goal of maximizing the efficacy and cost-effectiveness of therapy for anxiety disorders, which are some of the most prevalent mental conditions, making this a project of potentially high public health significance.

描述（由申请人提供）：本申请是对 PAR-12-071 的回应：用于精神障碍创新治疗试点研究的协作 R34（协作 R34）。 D-环丝氨酸 (DCS) 是一种 N-甲基-D-天冬氨酸谷氨酸部分激动剂，已被证明可以增强焦虑症的暴露疗法。这种方法基于最近在理解恐惧消退背后的神经回路方面取得的研究进展，并且基于转化研究的一项惊人成功。迄今为止，所有人体临床研究均在暴露前至少 1 小时进行 DCS。这种剂量计时策略限制了这种非常有前途的增强策略的临床实用性，特别是正弦累积研究表明，DCS 增强暴露治疗结果的功效可能取决于暴露疗程的成功。临床前和初始临床数据表明，在成功的暴露疗程后，在灭绝试验后立即施用 DCS 也可以获得 DCS 暴露增强效果。拟议的研究建立在现有研究的基础上，通过测试定制的会话后 DCS 管理（即仅在成功的暴露会话之后）对于增强暴露疗法的功效。为了在这项 R34 研究中保持较高的内部有效性，我们将在先前验证的 5 次 CBT 方案中招募社交焦虑障碍 (SAD) 患者，并将他们随机分配到：(1) 定制的会后 DCS 给药； (2)会前DCS管理； (3) 安慰剂给药； (4) 非定制的会后 DCS 管理。主要结果将是社交焦虑严重程度的短期和长期改善：我们预计定制的会后 DCS 管理条件将优于会前 DCS 管理、安慰剂管理和非定制的会后 DCS 管理条件，分别在治疗后、1个月和3个月的随访中。此外，我们将探索为增强暴露治疗而定制的会后 DCS 给药效果的潜在调节因素。该应用程序是 DCS 研究中合乎逻辑的下一步。它为最终开发在 CBT 中实施 DCS 的算法迈出了第一步，为实现个性化医疗迈出了重要的创新一步，其目标是最大限度地提高焦虑症治疗的功效和成本效益，焦虑症是其中的一些最普遍的精神状况，使该项目具有潜在的高度公共卫生意义。

项目成果

Dose Timing of D-Cycloserine to Augment Exposure Therapy for Social Anxiety Disorder: A Randomized Clinical Trial.

D-环丝氨酸用于社交焦虑症增强暴露疗法的剂量时机：一项随机临床试验。

• DOI: 10.1001/jamanetworkopen.2020.6777
• 发表时间: 2020
• 期刊: JAMA network open
• 影响因子: 13.8
• 作者: Smits,JasperAJ;Pollack,MarkH;Rosenfield,David;Otto,MichaelW;Dowd,Sheila;Carpenter,Joseph;Dutcher,ChristinaD;Lewis,ElizabethM;Witcraft,SaraM;Papini,Santiago;Curtiss,Joshua;Andrews,Leigh;Kind,Shelley;Conroy,Kristina;Hofman
• 通讯作者: Hofman

Sleep quality and outcome of exposure therapy in adults with social anxiety disorder.

• DOI: 10.1002/da.23167
• 发表时间: 2021-11
• 期刊: Depression and anxiety
• 影响因子: 7.4
• 作者: Dutcher CD;Dowd SM;Zalta AK;Taylor DJ;Rosenfield D;Perrone A;Otto MW;Pollack MH;Hofmann SG;Smits JAJ
• 通讯作者: Smits JAJ