protocolSection identificationModule nctId: NCT06308653, orgStudyIdInfo id: PSIL301, briefTitle: Psilocybin for Major Depressive Disorder (MDD), acronym: uAspire, statusModule overallStatus: RECRUITING, startDateStruct date: 2024-03-05, primaryCompletionDateStruct date: 2025-04, completionDateStruct date: 2026-04, studyFirstPostDateStruct date: 2024-03-13, lastUpdatePostDateStruct date: 2024-03-26, sponsorCollaboratorsModule leadSponsor name: Usona Institute, class: OTHER, descriptionModule briefSummary: Approximately 240 eligible adult participants (≥18 years old) who meet Diagnostic and Statistical Manual of Mental Disorders (DSM-5-TR) criteria for Major Depressive Disorder (MDD) will be enrolled. Participants will be randomly assigned to receive a single oral dose of Psilocybin 25 mg, Psilocybin 5 mg, or inactive placebo.The purpose of this study is to evaluate the efficacy, safety, and tolerability of Psilocybin 25 mg versus placebo in adults with MDD, as assessed by the difference between groups in change in depressive symptoms from Baseline to Day 43 post-dose, and to characterize the durability of initial treatment effect and subsequent response to optional Psilocybin 25 mg re-administration(s) during the 1-year Follow-up Period., conditionsModule conditions: Depressive Disorder, Major, designModule studyType: INTERVENTIONAL, phases: PHASE3, designInfo allocation: RANDOMIZED, interventionModel: PARALLEL, interventionModelDescription: Participants will be randomized to receive Psilocybin 25 mg, Psilocybin 5 mg, or inactive placebo under double-blind conditions. After the initial 6-week Double-blind Period, all participants will proceed into a 1-year Follow-up Period. During this 1-year Follow-up Period, eligible participants who meet pre-determined criteria may be offered open-label Psilocybin 25 mg in the context of a "Set and Setting" (SaS) Protocol., primaryPurpose: TREATMENT, maskingInfo masking: TRIPLE, maskingDescription: The following roles will be blinded to the treatment group assignment in the Double-blind Period during the trial: Participant, Investigator, Site Personnel, Facilitators, Efficacy Raters (including Site Raters, Participant Raters, and Central Raters), Contract Research Organization (CRO) Staff, and Sponsor.All roles other than the Sponsor, CRO, and Ethics Committees will also be blinded to the randomization ratio and Patient Health Questionnaire-9 (PHQ-9) score for re-administration eligibility.The Central MADRS Rater will also be blinded to all aspects of the protocol and trial visit for each participant.Blinded trial site personnel will complete administration of the IP.Full blinding of trial personnel, Sponsor, and participants will be maintained until database lock at the conclusion of the trial., whoMasked: PARTICIPANT, whoMasked: INVESTIGATOR, whoMasked: OUTCOMES_ASSESSOR, enrollmentInfo count: 240, type: ESTIMATED, armsInterventionsModule interventions name: Psilocybin 25 mg, interventions name: Inactive Placebo, interventions name: Psilocybin 5 mg, interventions name: Psychosocial Support, outcomesModule primaryOutcomes measure: Change in central rater Montgomery-Asberg Depression Rating Scale (MADRS) total score from Baseline to Trial Day 43, secondaryOutcomes measure: Change in central rater Clinical Global Impression-Severity (CGI-S) total score from Baseline to Trial Day 43, secondaryOutcomes measure: Change in on-site rater administered Sheehan Disability Scale (SDS) score from Baseline to post-dose Day 43, eligibilityModule sex: ALL, minimumAge: 18 Years, stdAges: ADULT, stdAges: OLDER_ADULT, contactsLocationsModule locations facility: Mountain View Clinical Research, status: RECRUITING, city: Denver, state: Colorado, zip: 80209, country: United States, contacts name: Brian Johnson, role: CONTACT, phone: 720-941-9363, phoneExt: 703, email: Brian@mtnresearch.com, contacts name: David Weiss, MD, role: PRINCIPAL_INVESTIGATOR, geoPoint lat: 39.73915, lon: -104.9847, locations facility: Innovative Clinical Research, Inc., status: RECRUITING, city: Lauderhill, state: Florida, zip: 33319, country: United States, contacts name: Shelbie Bobrow, role: CONTACT, phone: 954-769-1397, email: sbobrow@segaltrials.com, contacts name: Louis Sotolongo, role: CONTACT, phone: 954-769-1397, email: lsotolongo@segaltrials.com, contacts name: Rishi Kakar, MD, role: PRINCIPAL_INVESTIGATOR, geoPoint lat: 26.14036, lon: -80.21338, locations facility: Cedar Clinical Research, status: RECRUITING, city: Draper, state: Utah, zip: 84020, country: United States, contacts name: Jane Bjorklund, role: CONTACT, phone: 801-369-4219, email: jane.bjorklund@numinus.com, contacts name: Reid Robison, MD, role: PRINCIPAL_INVESTIGATOR, geoPoint lat: 40.52467, lon: -111.86382, locations facility: Cedar Clinical Research, Inc., status: RECRUITING, city: Murray, state: Utah, zip: 84107, country: United States, contacts name: Jane Bjorklund, role: CONTACT, phone: 801-369-4219, email: jane.bjorklund@numinus.com, contacts name: Paul Thielking, MD, role: PRINCIPAL_INVESTIGATOR, geoPoint lat: 40.66689, lon: -111.88799, hasResults: False