Clinical trial NCT06308653: Psilocybin for Major Depressive Disorder (MDD)
Official title: A Phase 3, Randomized, Double-Blind, Multicenter Study to Evaluate the Efficacy, Safety, and Tolerability of Psilocybin in Adults With Major Depressive Disorder (MDD)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Depressive Disorder, Major
Keywords: Psilocybin
Psychedelic
Depression
Major Depressive Disorder
MDD
Psychosocial
Psychoeducation
Set and Setting
Lead sponsor: Usona Institute
Sponsor class: OTHER
First posted: 2024-03-13
Enrollment: 240
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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.
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: Double-blind Period:

Participants who show stable depression symptoms between Screening and Trial Baseline will be randomly assigned to receive a single oral dose of Psilocybin 25 mg, Psilocybin 5 mg, or inactive placebo.

Investigational Product (IP) will be administered in the context of a "Set and Setting" (SaS) Protocol for psychosocial support, comprised of 1) a period of preparation with Facilitators prior to dosing; 2) administration of IP in an aesthetically pleasing room under the supervision of two Facilitators; and 3) post-dose integration sessions during which participants will discuss their dosing experience with the Facilitators.

Trial outcome measures will assess depressive symptoms, functional disability, health-related quality of life, and clinical global impression of disease severity.

Long-term Follow-up Period:

After the initial 6-week Double-blind Period and completion of the post-dosing Trial Day 43 assessments, all participants will proceed into a 1-year Follow-up Period.

During the 1-year Follow-up Period, participants will be followed regularly by clinic staff to assess MDD symptom severity, functional disability, and health-related quality of life; long-term safety data will also be collected. In addition to scheduled clinic visits, clinic staff will contact participants by telephone every two weeks to assess for changes in MDD symptom severity, concomitant medications, adverse events (AEs), and suicidal ideation and behavior.

Participants who meet the pre-defined MDD severity criteria and meet all re-administration eligibility criteria may be offered re-administration(s) of open-label Psilocybin 25 mg administered under a "Set and Setting" (SaS) Protocol. Psychosocial support, including psychoeducation, is also incorporated in the long-term Follow-up Period.

Eligibility criteria: Inclusion Criteria:

* Adults ≥18 years old.
* Able to swallow capsules.
* If of childbearing potential, agree to practice an effective means of birth control throughout the duration of the study.
* Meet the DSM-5-TR criteria for a diagnosis of major depressive disorder and are currently experiencing a major depressive episode of at least a 60-day duration at the time of Screening.
* Have at least moderate severity of depression symptoms at Screening and Trial Baseline.

Exclusion Criteria:

* Participants who are pregnant, who intend to become pregnant during the trial, or who are currently nursing.
* Have any of the following cardiovascular conditions: coronary artery disease, congenital long QT syndrome, cardiac hypertrophy, cardiac ischemia, congestive heart failure, clinically-relevant valvular heart disease, pulmonary hypertension, myocardial infarction, a clinically significant ECG abnormality, or tachycardia.
* Have elevated blood pressure.
* Have neurological conditions such as stroke, including transient ischemic attack, epilepsy, neurodegenerative disease (e.g., dementia, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, etc.), or brain tumor.
* Have severe hepatic or renal impairment.
* Have uncontrolled diabetes mellitus or unstable existing thyroid disorder.
* Are hepatitis or HIV positive.
* Have a positive urine drug test for illicit, non-prescribed, or prohibited substances.
* Meet DSM-5-TR criteria for schizophrenia spectrum or other psychotic disorders, including major depressive disorder with psychotic features ,bipolar disorder (types 1 or 2), antisocial personality disorder, borderline personality disorder or moderate or severe alcohol or drug use disorder
* Meet DSM-5-TR criteria for active post-traumatic stress disorder within 6 months prior to Screening.
* Have a first-degree relative with schizophrenia spectrum or other psychotic disorders, or bipolar I disorder.

Primary outcomes:
measure: Change in central rater Montgomery-Asberg Depression Rating Scale (MADRS) total score from Baseline to Trial Day 43
timeFrame: From Trial Baseline to Trial Day 43
Secondary outcomes:
measure: Change in central rater Clinical Global Impression-Severity (CGI-S) total score from Baseline to Trial Day 43
timeFrame: From Trial Baseline to Trial Day 43
measure: Change in on-site rater administered Sheehan Disability Scale (SDS) score from Baseline to post-dose Day 43
timeFrame: From Trial Baseline to Trial Day 43
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama Clinical Research Unit
state: Alabama
city: Fayetteville
country: United States
facility: Preferred Research Partners-NWA, LLC
state: Arkansas
city: Little Rock
country: United States
facility: Preferred Research Partners, Inc.
state: Arkansas
city: La Jolla
country: United States
facility: Kadima Neuropsychiatry Institute
state: California
city: Los Angeles
country: United States
facility: West LA VA Medical Center - Mental Health Department
state: California
city: Santa Monica
country: United States
facility: Pacific Neuroscience Institute (PNI) at Saint John's Physician Partners
state: California
city: Denver
country: United States
facility: Mountain View Clinical Research
state: Colorado
city: New Haven
country: United States
facility: Connecticut Mental Health Center, Yale University
state: Connecticut
city: Jacksonville
country: United States
facility: Clinical Neuroscience Solutions Inc.
state: Florida
city: Lauderhill
country: United States
facility: Innovative Clinical Research, Inc.
state: Florida
city: Orlando
country: United States
facility: Clinical Neuroscience Solutions, Inc.
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Decatur
country: United States
facility: CenExel iResearch, LLC
state: Georgia
city: Chicago
country: United States
facility: Great Lakes Clinical Trials
state: Illinois
city: Baltimore
country: United States
facility: Johns Hopkins School of Medicine, Center for Psychedelic and Consciousness Research
state: Maryland
city: Rockville
country: United States
facility: Sunstone Medical PC
state: Maryland
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Omaha
country: United States
facility: VA Nebraska Western Iowa Health Care System
state: Nebraska
city: Princeton
country: United States
facility: Global Medical Institutes, LLC; Princeton Medical Institute
state: New Jersey
city: Albuquerque
country: United States
facility: University of New Mexico (UNM) Interdisciplinary Substance Use and Brain Injury (ISUBI) Center
state: New Mexico
city: Bronx
country: United States
facility: Bronx Veterans Research Foundation at the James J. Peters VAMC
state: New York
city: New York
country: United States
facility: NYU Clinical & Translational Science Institute
state: New York
city: Moosic
country: United States
facility: Scranton Medical Institute, LLC
state: Pennsylvania
city: Plano
country: United States
facility: AIM Trials, LLC
state: Texas
city: San Antonio
country: United States
facility: Clinical Trials of Texas, LLC
state: Texas
city: Draper
country: United States
facility: Cedar Clinical Research
state: Utah
city: Murray
country: United States
facility: Cedar Clinical Research, Inc.
state: Utah
city: Bellevue
country: United States
facility: Seattle Neuropsychiatric Treatment Center
state: Washington
city: Vancouver
country: United States
facility: VA Portland Health Care System
state: Washington
Study officials:
References:
citation: Raison CL, Sanacora G, Woolley J, Heinzerling K, Dunlop BW, Brown RT, Kakar R, Hassman M, Trivedi RP, Robison R, Gukasyan N, Nayak SM, Hu X, O'Donnell KC, Kelmendi B, Sloshower J, Penn AD, Bradley E, Kelly DF, Mletzko T, Nicholas CR, Hutson PR, Tarpley G, Utzinger M, Lenoch K, Warchol K, Gapasin T, Davis MC, Nelson-Douthit C, Wilson S, Brown C, Linton W, Ross S, Griffiths RR. Single-Dose Psilocybin Treatment for Major Depressive Disorder: A Randomized Clinical Trial. JAMA. 2023 Sep 5;330(9):843-853. doi: 10.1001/jama.2023.14530.