Trial of a Glutamate Antagonist in the Treatment of OCD and Autistic Disorders

谷氨酸拮抗剂治疗强迫症和自闭症的试验

基本信息

批准号：
8342177
负责人：
Susan Swedo
金额：
$ 35.3万
依托单位：
NATIONAL INSTITUTE OF MENTAL HEALTH
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/8342177
关键词：
Adolescent Adult Affect Age Anxiety Disorders Autistic Disorder Behavior Behavior Therapy Behavioral Brain Chemicals Child Childhood Clinical Communication Comorbidity Complex Consensus Data Data Analyses Data Collection Depressive disorder Etiology Excitatory Amino Acid Antagonists Fluoxetine Fluvoxamine Frequencies Glutamates Goals Investigation Journals MRI Scans Magnetic Resonance Spectroscopy Medical Medicine Obsession Obsessive compulsive behavior Obsessive-Compulsive Disorder Outcome Measure Participant Patients Peer Review Pharmaceutical Preparations Pharmacotherapy Placebo Control Placebos Public Health Recruitment Activity Refractory Reporting Resistance Riluzole Ritual compulsion Safety Scanning Serious Adverse Event Serotonin Sertraline Severities Stereotyped Behavior Symptoms Work autism spectrum disorder cohort cost disability double-blind placebo controlled trial follow-up improved interest neurochemistry open label primary outcome psychologic reuptake social social cognition social communication success treatment response

项目摘要

The serotonin reuptake blocking medications (SSRIs, such as fluoxetine, fluvoxamine and sertraline) have been demonstrated to be efficacious in the treatment of obsessive-compulsive disorder (OCD), but many patients fail to respond to therapy. Treatment-refractory cases are particularly common among the comorbid ASD-OCD group, suggesting that modulation of serotonin alone is not sufficient for symptom relief in this cohort. The hypothesized etiology of childhood-onset OCD suggests that glutamate antagonists, such as riluzole, might reduce the severity of obsessions and compulsions because the drug works "upstream" from current pharmacotherapies. There has been some preliminary success in the use of riluzole for OCD among both adults and children. An open label trial of riluzole augmentation was conducted in 13 adult patients with treatment-resistant OCD. Concomitant medicines were continued during the trial and Yale-Brown Obsessive Compulsive Scale (Y-BOCS) scores improved significantly over the course of the investigation. Five subjects were categorized as treatment responders (Y-BOCS less than 16, and 35% or greater reduction in baseline score as well as clinical consensus improvement). Four of six pediatric subjects with OCD showed significant improvements after 12 weeks of open-label administration of riluzole; the treatment gains were sustained at one year follow-up with no serious adverse events reported. Compulsions, including simple, repetitive behaviors were improved as much as more complex rituals, suggesting that riluzole might be of benefit for the stereotyped behaviors of autism, as well as for the obsessions and compulsions. Autism spectrum disorders (ASD) are reported to affect as many as 1 in 150 children, with lifelong disabilities affecting social, communication and psychological functioning. With millions of children affected, ASD represents a tremendous public health problem. Compound the ASD symptoms with medical and psychiatric comorbidity, as frequently occurs, and the costs (in both dollars and suffering) are immense. Currently, there are no medications with demonstrated benefits for any of the three core symptoms of autism (social deficits, communication abnormalities and fixated interests/repetitive behaviors). Although some behavioral strategies are reported to be useful for the social and communication spheres, no behavioral interventions have shown consistent benefits for the fixated interests and repetitive behaviors of ASD. However, given the close similarity between these symptoms and the obsessive-compulsive behaviors seen in childhood-onset obsessive-compulsive disorder (OCD), and the frequency with which OCD is present as a comorbidity in ASD, we postulated that medications which reduce OCD symptoms might also improve the repetitive behaviors and fixated interests of ASD. During the study period, data collection was completed for a 12-weeks long, placebo-controlled investigation assessing safety and efficacy of riluzole for the treatment of obsessive-compulsive symptoms among 60 children and adolescents(ages 7 to 17 years)with OCD, up to 30 of whom also had ASD. Data analysis is currently underway and it is expected that we will find riluzole to be superior to placebo in reducing obsessive-compulsive symptom severity, and possibly the frequency and intensity of ASD-related stereotyped behaviors and fixated interests. Overall behavior is also expected to improve. A study of the neurochemical effects of riluzole treatment is underway, utilizing magnetic resonance spectroscopy (MRS). Children and adolescents who participate in the investigation will undergo an MRS scan (similar to an MRI scan) before starting treatment with riluzole and during treatment. Changes in brain concentrations of glutamate and related chemicals will be assessed and compared with symptom severity and degree of treatment response. The MRS study is currently recruiting subjects and further information about the investigation can be found at ClinicalTrials.gov with study identifier: NCT01019967

血清素再摄取阻断药物（SSRI，例如氟西汀，氟氟众和舍曲雷）已被证明可以有效治疗强迫症（OCD），但许多患者未能应对治疗。在合并症ASD-OCD组中，治疗难治性病例尤为常见，这表明单独调节5-羟色胺不足以缓解该队列中的症状。儿童期强迫症的假设病因表明，谷氨酸拮抗剂（例如riluzole）可能会减少痴迷和强迫性的严重程度，因为该药物从当前的药物治疗中“上游”。在成人和儿童中，在Riluzole使用Riluzole方面取得了一些初步的成功。对13例耐药性强迫症患者进行了Riluzole增强的开放标签试验。在试验期间继续进行伴随的药物，在整个研究过程中，耶鲁棕色的强迫性量表（Y-BOC）得分显着提高。将五名受试者归类为治疗响应者（Y-BOC小于16，基线评分降低35％或更高，以及临床共识的改善）。六个患有强迫症的儿科受试者中有四名在开放标签的Riluzole经过12周后显示出显着改善。一年随访的治疗收益持续，没有报道严重的不良事件。包括简单的重复行为在内的强迫症和更复杂的仪式得到了改善，这表明Riluzole可能对自闭症的刻板印象以及对痴迷和强迫有益。据报道，自闭症谱系障碍（ASD）影响了150名儿童中多达1个，终生残疾影响社会，沟通和心理功能。 ASD有数百万儿童受到影响，代表了一个巨大的公共卫生问题。复合了ASD症状与医学和精神病合并症的频率一样，而且成本（以美元和苦难都）巨大。当前，对于自闭症的三种核心症状（社会缺陷，沟通异常和固定的利益/重复行为）的三种核心症状中的任何一种药物都没有证明的好处。尽管据报道某些行为策略对于社会和沟通领域很有用，但没有行为干预措施显示出对固定利益和ASD重复行为的一致好处。但是，鉴于这些症状与儿童强迫症（OCD）中看到的强迫性行为之间的相似之处，以及ASD中强迫症作为合并症的频率，我们假设减少OCD症状的药物也可能会改善重复的行为和ASD的固定利益。在研究期间，为长达12周的安慰剂对照研究完成了数据收集，评估了Riluzole对60名儿童和青少年（7至17岁）强迫症的强迫症治疗的安全性和功效，其中有OCD，其中30名儿童和青少年也有30名儿童和青少年。目前正在进行数据分析，预计我们会发现里卢佐尔在减少强迫症的症状严重程度以及ASD与ASD相关的刻板印象和固定兴趣的频率和强度方面比安慰剂优于安慰剂。总体行为也有望改善。利用磁共振光谱法（MRS），正在对Riluzole处理的神经化学作用进行研究。参加调查的儿童和青少年将在开始使用Riluzole和治疗期间进行治疗之前，将接受MRS扫描（类似于MRI扫描）。将评估谷氨酸和相关化学物质的大脑浓度的变化，并将其与症状严重程度和治疗反应程度进行比较。 MRS研究目前正在招募主题，有关该研究的进一步信息可以在clinicaltrials.gov上找到，并带有研究标识符：NCT01019967