Clinical trial NCT06512194: Investigation to Understand and Optimize Psilocybin
Official title: An Investigation of Strategies to Understand and Optimize the Antidepressant Effects of Psilocybin (The OPTIMIZE Study)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Depression
Keywords: depression
psilocybin
psychedelics
transcutaneous auricular vagus nerve stimulation
depressive symptoms
well-being
adverse events
ecological momentary assessment
electronically activated recorder
dynamical complexity assessment
Lead sponsor: Vail Health Behavioral Health
Sponsor class: OTHER
Collaborators: name: Usona Institute
name: Tiny Blue Dot Foundation
name: Steadman Philippon Research Institute
name: Emory University
First posted: 2024-07-22
Enrollment: 141
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: All subjects will receive a single 25 mg dose of psilocybin administered within a "set and setting" (SaS) framework of psychological support provided by trained clinicians. Post-dosing, subjects will be randomized to 1) taVNS, 2) sham taVNS, or 3) no taVNS.
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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 subjects.

All subjects 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, subjects 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.

Eligibility criteria: Inclusion Criteria:

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.

Exclusion Criteria:

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.

Primary outcomes:
measure: Montgomery-Åsberg Depression Rating Scale (MADRS) score
timeFrame: Baseline 2, Week 8 Post-Psilocybin Dosing
measure: PROMIS Ability to Participate in Social Roles and Activities - Short Form 8a
timeFrame: Baseline 2, Week 8 Post-Dose
measure: Quality of Life Enjoyment and Satisfaction Questionnaire Short-Form (Q-LES-Q) score
timeFrame: Baseline 2, Week 8 Post-Dose
Secondary outcomes:
measure: Electronically Activated Recorder (EAR)
timeFrame: Up to 55 days
measure: Voicediary
timeFrame: Up to 35 days
measure: Ecological Momentary Assessment (EMA)
timeFrame: Up to 35 days
measure: Challenging Experiences Questionnaire (CEQ) score
timeFrame: Day 1 Post-Dose, Week 8 Post-Dose
measure: Warwick-Edinburgh Mental Wellbeing Scale (WEMWBS) score
timeFrame: Baseline 1, Baseline 2, Week 2 Post-Dose, Week 4 Post-Dose, Week 8 Post-Dose
measure: Psychedelic Assisted Therapy Adverse Events (PATAE)
timeFrame: Baseline 1, Baseline 2, Day 1 Post-Dose, Week 1 Post-Dose, Week 2 Post-Dose, Week 4 Post-Dose, Week 8 Post-Dose
measure: 30-item Mystical Experiences Questionnaire (MEQ30) score
timeFrame: Day 1 Post-Dose, Week 8 Post-Dose
measure: Emotional Breakthrough Inventory (EBI) score
timeFrame: Day 1 Post-Dose, Week 8 Post-Dose
measure: Psychological Insight Questionnaire (PIQ) score
timeFrame: Day 1 Post-Dose, Week 8 Post-Dose
measure: Ego Dissolution Inventory (EDI) score
timeFrame: Day 1 Post-Dose, Week 8 Post-Dose
measure: Awe Experiences Questionnaire - Short Form (AWE-SF) score
timeFrame: Day 1 Post-Dose, Week 8 Post-Dose
Other outcomes:
Locations:
city: Edwards
country: United States
facility: Vail Health Behavioral Health
state: Colorado
Study officials:
affiliation: Vail Health Behavioral Health
name: Charles Raison, MD
role: PRINCIPAL_INVESTIGATOR
References: