Psilocybin for Major Depressive Disorder (MDD)

Depressive Disorder, Major Clinical Trial

— uAspire  

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06308653
• Other study ID #: PSIL301
• Status: Recruiting
• Phase: Phase 3
• Start date: March 5, 2024
• Est. completion date: April 2026

Study information

• Verified date: May 2024
• Source: Usona Institute
• Contact: Kasia Warchol
• Phone: 608-210-6016
• Email: ClinicalTrials[@]usonainstitute.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 240
• Est. completion date: April 2026
• Est. primary completion date: April 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Major

Intervention

Drug:
• Psilocybin 25 mg
The Psilocybin used in this study is synthetically manufactured in a laboratory and meets quality specifications suitable for human research use. The active drug is encapsulated within a hydroxypropyl methylcellulose (HPMC) capsule and contains 25 mg of Psilocybin.
• Inactive Placebo
The inactive placebo is encapsulated within a hydroxypropyl methylcellulose (HPMC) capsule and contains 25 mg of Microcrystalline Cellulose (MCC). The MCC is synthetically manufactured in a laboratory and meets quality specifications suitable for human research use.
• Psilocybin 5 mg
The Psilocybin used in this study is synthetically manufactured in a laboratory and meets quality specifications suitable for human research use. The active comparator is encapsulated within a hydroxypropyl methylcellulose (HPMC) capsule and contains 5 mg of Psilocybin.

Behavioral:
• Psychosocial Support
Psychosocial Support, including psychoeducation, begins after the Double-blind Period and continues throughout the 1-year Follow-up Period in order to enhance participant safety and maximize retention for the entire trial duration.

Locations

Country	Name	City	State
United States	Great Lakes Clinical Trials	Chicago	Illinois
United States	CenExel iResearch, LLC	Decatur	Georgia
United States	Mountain View Clinical Research	Denver	Colorado
United States	Cedar Clinical Research	Draper	Utah
United States	Clinical Neuroscience Solutions Inc.	Jacksonville	Florida
United States	Innovative Clinical Research, Inc.	Lauderhill	Florida
United States	Preferred Research Partners, Inc.	Little Rock	Arkansas
United States	Cedar Clinical Research, Inc.	Murray	Utah
United States	Clinical Neuroscience Solutions, Inc.	Orlando	Florida
United States	Global Medical Institutes, LLC; Princeton Medical Institute	Princeton	New Jersey

Sponsors (1)

Lead Sponsor	Collaborator
Usona Institute

Country where clinical trial is conducted

United States, 

References & Publications (1)

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, — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in central rater Montgomery-Asberg Depression Rating Scale (MADRS) total score from Baseline to Trial Day 43	The MADRS is a clinician-rated scale designed to measure depression severity and to detect changes due to antidepressant treatment. The scale consists of 10 items, each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total possible score of 60. Higher scores represent a more severe condition. The total (composite) MADRS score is used as the endpoint.	From Trial Baseline to Trial Day 43
Secondary	Change in central rater Clinical Global Impression-Severity (CGI-S) total score from Baseline to Trial Day 43	The CGI-S is a 7-point scale, with a minimum score of 1 and a maximum score of 7, with higher scores representing more severe illness, that assesses the global severity of the participant's illness at the time of assessment relative to the clinician's past experience with patients who have the same diagnosis.	From Trial Baseline to Trial Day 43
Secondary	Change in on-site rater administered Sheehan Disability Scale (SDS) score from Baseline to post-dose Day 43	The SDS is a composite of three self-rated items designed to measure the extent to which three major sectors in the patient's life are impaired by psychiatric symptoms, including depression. The SDS total score ranges from 0 to 30 with higher representing greater functional disability.	From Trial Baseline to Trial Day 43