Effect of Psilocybin and Structured Integrated Reframing Therapy on Gut-Brain Axis Biomarkers and Depression in Trauma-Related Major Depressive Disorder: Randomized Controlled Trial
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 60
- 试验地点
- 3
- 主要终点
- Depression Severity
研究概览
简要总结
Trauma-related Major Depressive Disorder (MDD) is frequently associated with poor response to conventional antidepressants, persistent psychological distress, and alterations in gut-brain axis function. Existing assessment tools primarily diagnose depression or PTSD but provide limited guidance for integrated clinical management. This study aims to develop and validate the Trauma Anxiety Depression Emotion (TADE) management tool while simultaneously evaluating the effectiveness of psilocybin-assisted Structured Integrated Reframing Therapy (SIRT) in improving clinical and biological outcomes.
This prospective, four-arm randomized controlled trial will compare conventional therapy, psilocybin therapy, SIRT, and psilocybin-assisted SIRT. Participants will undergo assessment using the newly developed TADE tool together with established psychometric scales including HAM-D, PCL-5, and GAD-7. Biological outcomes will include serum gut-brain axis and inflammatory biomarkers, including Short-Chain Fatty Acids (SCFAs), Interleukin-6 (IL-6), Interleukin-10 (IL-10), Zonulin, Occludin, and Glial Cell Line-Derived Neurotrophic Factor (GDNF). Assessments will be performed at baseline, during treatment, and at 12-week follow-up. The study aims to determine whether combining psilocybin with SIRT provides superior clinical improvement and favorable biological changes compared with either intervention alone while establishing the validity and clinical utility of the TADE management tool.
详细描述
Major Depressive Disorder (MDD) is among the leading causes of disability worldwide. Individuals with trauma-related MDD frequently experience persistent depressive symptoms, anxiety, emotional dysregulation, post-traumatic stress symptoms, and impaired quality of life despite receiving conventional antidepressant therapy. Emerging evidence suggests that gut microbiota, intestinal permeability, immune activation, neuroplasticity, and inflammatory pathways contribute significantly to the pathophysiology of depression and trauma-related disorders.
This study integrates two novel innovations. First, it will develop and validate the Trauma Anxiety Depression Emotion (TADE) management tool, a comprehensive instrument designed to assess trauma exposure, PTSD symptoms, depression, anxiety, stress, emotional functioning, and treatment priorities. Second, it will evaluate Structured Integrated Reframing Therapy (SIRT), a newly developed psychotherapy integrating Cognitive Behavioral Therapy (CBT), Dialectical Behavior Therapy (DBT), mindfulness, cognitive reframing, and communication-focused therapeutic techniques.
The study is designed as a prospective, four-arm, parallel-group randomized controlled trial. Eligible participants with trauma-related Major Depressive Disorder will be randomly allocated to one of four intervention groups: (1) conventional therapy, (2) psilocybin therapy, (3) Structured Integrated Reframing Therapy (SIRT), or (4) psilocybin-assisted SIRT.
Clinical outcomes will be evaluated using the TADE tool together with validated psychometric instruments including the Hamilton Depression Rating Scale (HAM-D), PTSD Checklist for DSM-5 (PCL-5), and Generalized Anxiety Disorder-7 (GAD-7). Biological outcomes will include measurement of gut-brain axis and inflammatory biomarkers including Short-Chain Fatty Acids (SCFAs), Interleukin-6 (IL-6), Interleukin-10 (IL-10), Zonulin, Occludin, and Glial Cell Line-Derived Neurotrophic Factor (GDNF). Blood samples will be collected at baseline, Week 4, Week 8, and Week 12.
The primary objectives are to determine the effectiveness of psilocybin-assisted SIRT in reducing depressive symptoms and to validate the TADE management tool. Secondary objectives include evaluating changes in gut-brain axis biomarkers, determining correlations between biomarker changes and clinical improvement, and identifying biological predictors of treatment response. This integrated approach aims to provide evidence for a personalized treatment strategy that combines innovative psychotherapeutic interventions, psychedelic-assisted therapy, and biomarker-guided clinical management for trauma-related Major Depressive Disorder.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
盲法说明
This is an open-label study. Participants and treating clinicians will know the assigned intervention because psychotherapy and psilocybin administration cannot be practically blinded. Outcome measures will be collected using standardized validated instruments according to the study protocol.
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adults aged 18-60 years.
- •Diagnosis of Major Depressive Disorder (MDD) according to DSM-5 criteria.
- •Trauma-related depression with clinically significant trauma symptoms.
- •Hamilton Depression Rating Scale (HAM-D) score >
- •PTSD Checklist for DSM-5 (PCL-5) score >
- •Generalized Anxiety Disorder-7 (GAD-7) score >
- •Receiving a stable single SSRI antidepressant regimen for at least 6 weeks before enrollment with adequate treatment adherence.
- •Able and willing to provide written informed consent.
- •Willing to comply with all study procedures and follow-up visits.
- •Women of childbearing potential must agree to use effective contraception throughout the study.
排除标准
- •Significant cardiovascular disease.
- •Clinically significant hepatic or renal impairment.
- •Significant neurological disorders.
- •Current or past psychotic disorder or bipolar disorder.
- •Current substance or alcohol use disorder, including ketamine or psychedelic drug use.
- •Use of more than one antidepressant medication.
- •Pregnancy, planned pregnancy, or breastfeeding.
- •Known hypersensitivity or contraindication to psilocybin.
- •Participation in another interventional clinical trial within the previous 30 days.
- •Inability or unwillingness to provide informed consent.
- •Any medical or psychiatric condition that, in the investigator's opinion, would interfere with safe participation or study assessments.
研究组 & 干预措施
Conventional Therapy (Control)
Participants will receive standard conventional treatment for trauma-related Major Depressive Disorder, consisting of a stable selective serotonin reuptake inhibitor (SSRI) regimen prescribed by the treating psychiatrist. No psilocybin or Structured Integrated Reframing Therapy (SIRT) will be administered. Treatment will continue for 8 weeks with routine clinical follow-up.
干预措施: Selective Serotonin Reuptake Inhibitor (SSRI) (Drug)
Psilocybin Therapy
Participants will continue standard SSRI therapy and receive oral psilocybin administered under medical supervision in a controlled clinical setting. Two supervised dosing sessions will be conducted during the 8-week intervention period according to the study protocol. No SIRT will be provided.
干预措施: Selective Serotonin Reuptake Inhibitor (SSRI) (Drug)
Structured Integrated Reframing Therapy (SIRT)
Participants will continue standard SSRI therapy and receive Structured Integrated Reframing Therapy (SIRT), a trauma-informed psychotherapy integrating Cognitive Behavioral Therapy (CBT), Dialectical Behavior Therapy (DBT), mindfulness, cognitive reframing, and communication-focused therapeutic techniques. Therapy will be delivered once weekly for 8 weeks by trained therapists.
干预措施: Structured Integrated Reframing Therapy (SIRT) (Behavioral)
Structured Integrated Reframing Therapy (SIRT)
Participants will continue standard SSRI therapy and receive Structured Integrated Reframing Therapy (SIRT), a trauma-informed psychotherapy integrating Cognitive Behavioral Therapy (CBT), Dialectical Behavior Therapy (DBT), mindfulness, cognitive reframing, and communication-focused therapeutic techniques. Therapy will be delivered once weekly for 8 weeks by trained therapists.
干预措施: Selective Serotonin Reuptake Inhibitor (SSRI) (Drug)
Psilocybin-Assisted Structured Integrated Reframing Therapy
Participants will continue standard SSRI therapy and receive both supervised oral psilocybin administration and Structured Integrated Reframing Therapy (SIRT). Psilocybin will be administered in two supervised dosing sessions during the 8-week intervention period, while SIRT will be delivered once weekly for 8 weeks. The combined intervention is intended to evaluate the synergistic effects of psychedelic-assisted psychotherapy on clinical outcomes and gut-brain axis biomarkers.
干预措施: Structured Integrated Reframing Therapy (SIRT) (Behavioral)
Psilocybin-Assisted Structured Integrated Reframing Therapy
Participants will continue standard SSRI therapy and receive both supervised oral psilocybin administration and Structured Integrated Reframing Therapy (SIRT). Psilocybin will be administered in two supervised dosing sessions during the 8-week intervention period, while SIRT will be delivered once weekly for 8 weeks. The combined intervention is intended to evaluate the synergistic effects of psychedelic-assisted psychotherapy on clinical outcomes and gut-brain axis biomarkers.
干预措施: Selective Serotonin Reuptake Inhibitor (SSRI) (Drug)
Psilocybin Therapy
Participants will continue standard SSRI therapy and receive oral psilocybin administered under medical supervision in a controlled clinical setting. Two supervised dosing sessions will be conducted during the 8-week intervention period according to the study protocol. No SIRT will be provided.
干预措施: Psilocybin (Drug)
Psilocybin-Assisted Structured Integrated Reframing Therapy
Participants will continue standard SSRI therapy and receive both supervised oral psilocybin administration and Structured Integrated Reframing Therapy (SIRT). Psilocybin will be administered in two supervised dosing sessions during the 8-week intervention period, while SIRT will be delivered once weekly for 8 weeks. The combined intervention is intended to evaluate the synergistic effects of psychedelic-assisted psychotherapy on clinical outcomes and gut-brain axis biomarkers.
干预措施: Psilocybin (Drug)
结局指标
主要结局
Depression Severity
时间窗: Baseline, Week 4, Week 8, and Week 12
Change in depression severity measured using the Hamilton Depression Rating Scale (HAM-D-17). The HAM-D-17 is a clinician-administered scale with a total score ranging from 0 to 52, where higher scores indicate more severe depressive symptoms. The outcome will be reported as the change in total HAM-D-17 score from baseline.
Trauma-Related Symptoms
时间窗: Baseline, Week 4, Week 8, and Week 12
Change in trauma-related symptoms measured using the Posttraumatic Stress Disorder Checklist for DSM-5 (PCL-5). The PCL-5 is a self-report questionnaire with a total score ranging from 0 to 80, where higher scores indicate more severe PTSD symptoms. The outcome will be reported as the change in total PCL-5 score from baseline.
Anxiety Severity
时间窗: Baseline, Week 4, Week 8, and Week 12
Change in anxiety severity measured using the Generalized Anxiety Disorder 7-item Scale (GAD-7). The GAD-7 is a self-report questionnaire with a total score ranging from 0 to 21, where higher scores indicate more severe anxiety symptoms. The outcome will be reported as the change in total GAD-7 score from baseline.
Gut-Brain Axis and Neuroinflammatory Biomarkers
时间窗: Baseline, Week 4, Week 8, and Week 12
Change in serum concentrations of gut-brain axis and neuroinflammatory biomarkers, including: Short-Chain Fatty Acids (SCFAs) Interleukin-6 (IL-6) Interleukin-10 (IL-10) Zonulin Occludin Glial Cell Line-Derived Neurotrophic Factor (GDNF) Biomarkers will be quantified using validated laboratory assays and reported in their respective concentration units (e.g., pg/mL or ng/mL, as appropriate).
次要结局
未报告次要终点