Searching for Exosomal microRNAs and Cellular Biomarkers and Mechanisms Underlying the Differences Between Panic Disorder Patients Who Are Responders and Non-responders to Cognitive Behavior Therapy
试验速览
- 阶段
- 不适用
- 入组人数
- 80
- 试验地点
- 2
- 主要终点
- Differntial expression of plasma exosomal microRNAs
研究概览
简要总结
Cognitive behavior therapy (CBT) has long been known as an effective treatment for anxiety disorders, either when given by a therapist or when self-administered through a computer program. However, the biological effect of CBT remained largely unexplored. Most studies focused on genomic differences and pursued differences in methylation patterns following CBT, but the findings were very limited in scope, especially when comparing responders and non-responders to CBT. In the currently proposed study, the investigators plan to go one step further and look for changes in exosomal microRNAs (miRs) from serum samples taken before and after CBT from Panic Disorder (PD) patients. Notably, miR changes show a much faster biological response than methylation patterns yet had never been used before in PD research. The primary benefit of this work will be in providing biological validation to psychological treatments. PD is a heavy public health burden, associated with significant market potential for both therapeutic and diagnostic uses.
详细描述
Cognitive Behavior Therapy (CBT) is an evidence-based treatment, commonly used for treating anxiety disorders. Patients with anxiety disorders are characterized by having cognitive distortions regarding evaluations of threat, which results in safety behaviors to avoid them thereby causing impairment in the patient's quality of life. CBT focuses on changing those "false beliefs" and "maladaptive behaviors" by exposing the patients to their anxiety source in a gradual way, supervised by the therapist.
Anxiety disorders are relatively common, and many people have difficulty accessing treatment due to a variety of obstacles. Researchers have therefore explored the possibility of using different methods to administer CBT, resulting in the making of internet-delivered CBT (iCBT). iCBT programs can involve therapist guidance through emails or can be entirely unguided. These programs are typically comprised of 6-15 modules, which are text chapters corresponding to sessions in face-to-face therapy. These programs require little therapist involvement other than guidance and feedback on homework assignments. Current meta-analyses suggest that iCBT does not differ from regular CBT in its efficacy, conducted through a guided program.
In this study, the investigators plan to examine whether iCBT and regular CBT can cause biological changes as well as cognitive ones. Few previous studies have shown epigenetic changes in different directions for CBT responders and non-responders. Those studies used methylation patterns as biomarkers, showing that Panic Disorder (PD) patients had lower methylation in specific genes than the control group at the baseline point. After going through CBT the responders showed higher methylation and the non-responders showed even lower methylation than at the baseline point. In addition, a more recent study showed that in comparison to healthy controls, PD patients showed changes in immune system activities. Microglial acid sensing G-protein coupled receptor and T cell death-associated gene-8 (TDAG8), which was found was found higher in PD patients.
The investigators wish to take these findings one step forward by using micro-RNAs (miRs) content of circulation exosomes as our biomarker. Exosomes are a type of extracellular vesicles of endocytic origin, used in signaling and cell to cell communication, by transferring proteins, lipids, and variety of RNAs between cells. miRs are short single-stranded RNA molecules that bind to complementary sequences of target mRNAs, causing inhibition of their translation and/or inducing target degradation and affecting brain functioning and mental processes.
The investigators will base their work on the hypothesis that the brain's state is reflected, to a certain extent in the miR contents of circulating exosomes. Therefore, the aim of the study will be to test the difference between patients and controls as well as between responders and non-responders by profiling miRs content of circulation exosomes from their plasma samples and seeking association with their clinical data. Whole blood samples will also be collected, in order to serve as secondary outcome measurement, checking for changes in expression of other small non-coding circulating RNAs as well.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Principal DSM-5 primary diagnosis of panic disorder and/or agoraphobia.
- •Aged 18 years or older.
- •PD duration of at least 3 months.
- •If participant is on on medications for PD, the dosage has to remain constant for 3 months prior to the start of treatment and cannot be increased during treatment.
- •The participant must have access to the internet and be willing to use it.
排除标准
- •Substance abuse or dependence within the last 6 months.
- •Active suicide potential within the last 6 months.
- •Any current or history of psychosis or bipolar I disorder.
- •Currently in weekly or biweekly psychotherapy.
- •History of a complete course of panic focused CBT
结局指标
主要结局
Differntial expression of plasma exosomal microRNAs
时间窗: Pre and post treatment, up to 6 months apart.
Exosomes are a type of extracellular vesicles of endocytic origin, used in signalling and cell to cell communication, by transferring proteins, lipids, and variety of RNAs between cells. miRs are short single-stranded RNA molecules that bind to complementary sequences of target mRNAs, causing inhibition of their translation and/or inducing target degradation and affecting brain functioning and mental processes. Will be measured twice: pre and post treatment (post or 6 months, whichever is later, to the maximum of 6 months).
次要结局
- Change in the Five-Dimensional Curiosity Scale (DCS-5)(Pre and post treatment, up to 6 months apart.)
- Change in Anxiety Sensitivity Index-3 (ASI-3)(Weekly during treatment and at pre and post treatment evaluations, up to 6 months apart.)
- Changes in Experiences in Close Relationship Scale-Short (ECR-s)(Pre and post treatment, up to 6 months apart.)
- Change in Panic Disorder Severity Scale (PDSS)(Weekly during treatment and at pre and post treatment evaluations, up to 6 months apart.)
- Change in Mobility Inventory(Weekly during treatment and at pre and post treatment evaluations, up to 6 months apart.)
- Differntial expression of whole Blood short non-coding RNAs(Pre and post treatment, up to 6 months apart.)
- Changes in Sexual Functioning Questionnaire(Pre and post treatment, up to 6 months apart.)
研究者
Jonathan D. Huppert
Professor
Hebrew University of Jerusalem