An Investigation of Strategies to Understand and Optimize the Antidepressant Effects of Psilocybin (The OPTIMIZE Study)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 141
- 试验地点
- 1
- 主要终点
- Montgomery-Åsberg Depression Rating Scale (MADRS) score
研究概览
简要总结
This study will examine the effects of a single dose of psilocybin, administered with psychological support, on symptoms of depression. It will also assess whether different post-dosing interventions, including a non-invasive technique called transcutaneous auricular Vagus Nerve Stimulation (taVNS), influence various psychological and behavioral outcomes. In addition, the study will explore objective measures of real-world social behavior and identify early behavioral responses that may be associated with long-term treatment outcomes.
详细描述
One hundred forty-one adults ages 18 to 70 experiencing a major depressive episode of at least 60 days duration of moderate or greater severity at screening will be enrolled to obtain evaluable data on approximately 120 participants.
All participants will receive a single 25 mg dose of psilocybin using a "set and setting" therapeutic approach that will include 1) several hours of preparatory sessions prior to dosing and 2) the presence of two facilitators throughout the dosing session; and 3) several post dosing integration sessions with a facilitator.
Following the psilocybin dosing session, participants will be randomized to 1) taVNS (7 days of twice daily taVNS), 2) sham taVNS (7 days of twice daily sham taVNS), or 3) no taVNS.
Both taVNS and sham sessions will include guided prompts encouraging participants to reflect on key aspects of their psychedelic experience, accompanied by music previously used during the psilocybin dosing session.
Participants will complete assessments at multiple time points to evaluate depression, anxiety, well-being, functional disability, quality of life, social behavior, suicidal ideation, and adverse events before and after psilocybin dosing.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Current diagnosis of Major Depressive Disorder (MDD), with a depressive episode lasting ≥ 60 consecutive days at the time of screening, as confirmed by structured clinical interview
- •Medically healthy, as determined by the screening physician, with no significant medical conditions that would interfere with participation or affect the safety of the subject.
排除标准
- •History or presence of any psychiatric or medical condition that, in the opinion of the investigator, could pose a safety risk, interfere with participation, or confound study results (e.g., bipolar disorder, psychosis, seizure disorder, or cardiovascular disease).
- •Known family history of a psychotic disorder (e.g., schizophrenia or schizoaffective disorder) in a first-degree relative (biological parent, full sibling, or child).
- •Current active suicidal ideation with a specific plan within the prior 2 weeks, as assessed via clinical interview and validated instrument (e.g., C-SSRS).
- •Suicide attempt within the prior 6 months, regardless of intent or lethality.
- •Current diagnosis of a substance use disorder
- •Abnormal ECG at screening that may increase risk during participation (e.g., prolonged QTc, arrhythmias, or other clinically significant findings as determined by the study physician).
- •Unwilling or unable to discontinue prescription psychotropic medications (e.g., antidepressants, antipsychotics, anxiolytics, lithium, anticonvulsants, or mood stabilizers) for the duration of study participation, including any necessary washout period as determined by the investigator.
- •Any condition, finding, or behavior (including suspected deception or noncompliance) that, in the opinion of the investigator, renders the participant unsuitable for the study or likely to interfere with the integrity of the data or safety of the subject.
研究组 & 干预措施
Group 1: Psilocybin + taVNS
Participants in this arm will receive a single 25 mg dose of psilocybin, followed by twice-daily sessions of taVNS for 7 consecutive days. Each taVNS session will be paired with music and prompts related to the participant's psilocybin experience.
干预措施: Transcutaneous Auricular Vagus Nerve Stimulation (taVNS) (Device)
Group 2: Psilocybin + Sham taVNS
Participants in this arm will receive a single 25 mg dose of psilocybin, followed by twice-daily sham taVNS sessions for 7 consecutive days. Each sham session will be paired with music and prompts related to the participant's psilocybin experience.
干预措施: Sham taVNS (Device)
Group 1: Psilocybin + taVNS
Participants in this arm will receive a single 25 mg dose of psilocybin, followed by twice-daily sessions of taVNS for 7 consecutive days. Each taVNS session will be paired with music and prompts related to the participant's psilocybin experience.
干预措施: Psilocybin (Drug)
Group 3: Psilocybin + No taVNS
Participants in this arm will receive a single 25 mg dose of psilocybin, followed by no additional intervention. They will receive the standard psychological support related to their psilocybin experience, but no taVNS or sham device will be used.
干预措施: Psilocybin (Drug)
Group 2: Psilocybin + Sham taVNS
Participants in this arm will receive a single 25 mg dose of psilocybin, followed by twice-daily sham taVNS sessions for 7 consecutive days. Each sham session will be paired with music and prompts related to the participant's psilocybin experience.
干预措施: Psilocybin (Drug)
结局指标
主要结局
Montgomery-Åsberg Depression Rating Scale (MADRS) score
时间窗: Baseline 2, Week 8 Post-Psilocybin Dosing
The MADRS is a 10-item depression rating scale that includes questions on the following symptoms: 1. Reported sadness, 2. Apparent sadness, 3. Inner tension, 4. Reduced sleep, 5. Reduced appetite, 6. Concentration difficulties, 7. Lassitude, 8. Inability to feel, 9. Pessimistic thoughts, and 10. Suicidal thoughts. Items are scored via a blinded clinical interview and rated to capture the patient's clinical state over the prior week. Each item yields a score of 0 to 6, and higher scores indicate more severe depression. The overall score ranges from 0 to 60. For this study, the structured MADRS interview will be used.
PROMIS Ability to Participate in Social Roles and Activities - Short Form 8a
时间窗: Baseline 2, Week 8 Post-Dose
An 8-item validated measure assessing an individual's perceived ability to engage in social roles and activities, such as work, family responsibilities, and leisure. Participants rate each item on a 5-point Likert scale. Total score can range from 8 to 40 with higher scores indicating greater functional ability and social participation.
Quality of Life Enjoyment and Satisfaction Questionnaire Short-Form (Q-LES-Q) score
时间窗: Baseline 2, Week 8 Post-Dose
The Short Form version (Q-LES-Q-SF) will be used in this trial. The measure contains 16 items that assess quality of life. A total score is derived from summing the first 14 items on the scale, with the last 2 items serving as stand-alone queries. Total score can range from 14 to 70 with higher scores indicating better quality of life.
次要结局
- Electronically Activated Recorder (EAR)(Up to 55 days)
- Voicediary(Up to 35 days)
- Ecological Momentary Assessment (EMA)(Up to 35 days)
- Challenging Experiences Questionnaire (CEQ) score(Day 1 Post-Dose, Week 8 Post-Dose)
- Warwick-Edinburgh Mental Wellbeing Scale (WEMWBS) score(Baseline 1, Baseline 2, Week 2 Post-Dose, Week 4 Post-Dose, Week 8 Post-Dose)
- Psychedelic Assisted Therapy Adverse Events (PATAE)(Baseline 1, Baseline 2, Day 1 Post-Dose, Week 1 Post-Dose, Week 2 Post-Dose, Week 4 Post-Dose, Week 8 Post-Dose)
- 30-item Mystical Experiences Questionnaire (MEQ30) score(Day 1 Post-Dose, Week 8 Post-Dose)
- Emotional Breakthrough Inventory (EBI) score(Day 1 Post-Dose, Week 8 Post-Dose)
- Psychological Insight Questionnaire (PIQ) score(Day 1 Post-Dose, Week 8 Post-Dose)
- Ego Dissolution Inventory (EDI) score(Day 1 Post-Dose, Week 8 Post-Dose)
- Awe Experiences Questionnaire - Short Form (AWE-SF) score(Day 1 Post-Dose, Week 8 Post-Dose)
研究者
Charles Raison
Vail Health Behavioral Health Innovation Center Director
Vail Health Behavioral Health