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）：此申请响应PAR-12-071：用于精神疾病创新治疗的试点研究的R34协作R34（协作R34）。 D-胞克氨仁（DCS）是一种部分N-甲基-D-天冬氨酸谷氨酸激动剂，已显示可增强焦虑症的暴露疗法。最近的研究基于理解恐惧灭绝的神经回路的最新研究的基础，并基于转化研究的惊人成功之一。迄今为止，所有人类临床研究都至少在接触会议前1小时给予了DC。这种定量策略限制了这种高度有希望的增强策略的临床实用性，尤其是正弦积累的研究表明，DCS对增强暴露疗法结果的疗效可能取决于暴露会议的成功。临床前和初始临床数据表明，当在成功的暴露会话后，当DC在灭绝试验后立即管理DCS暴露效果。拟议的研究基于这项现有研究，通过测试量身定制的会议后DCS给药的功效（即仅在成功接触课程后）以增加暴露疗法。为了在这项R34研究中保持高度的内部有效性，我们将在先前验证的5份CBT方案中注册患有社交焦虑症的患者（SAD），并将其随机化为：（1）量身定制的后Session DCS管理； （2）会议前DCS管理； （3）安慰剂管理；或（4）未批准的会议后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：我们期望量身定制的会议后的DCS管理状况将优于会议前DCS管理，安慰剂管理和未付费的会议后DCS管理条件，分别在后期治疗，1个月和3个月的随访中。此外，我们将探讨量身定制的会议DCS管理功效以增加暴露疗法的潜在主持人。该应用程序是DC研究的逻辑下一步。它通过在最终开发CBT管理DC的算法中提供第一步，以最大程度地提高焦虑症治疗的疗效和成本效益，这是一些最普遍的精神状况，这是潜在的公共保健意义，这使得焦虑症的疗效和成本效益最大化，这为实现CBT的算法提供了第一步，从而为实现个性化医学的实现提供了重要的创新动作。

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