Clinical trial NCT03866174: A Study of Psilocybin for Major Depressive Disorder (MDD)
Official title: A Randomized, Double-Blind, Support-of-Concept Phase 2 Study of Single-Dose Psilocybin for Major Depressive Disorder (MDD)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Depressive Disorder, Major
Keywords: Psilocybin, Psychedelics, Depression, MDD
Lead sponsor: Usona Institute
Sponsor class: OTHER
Collaborators: name: The Emmes Company, LLC
First posted: 2019-03-07
Enrollment: 104
Sex: ALL
Minimum age (years): 21
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: One hundred participants, ages 21 to 65, who meet Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria for major depressive disorder (MDD) will be stratified by study site and randomized with a 1-to-1 allocation under double-blind conditions to receive a single 25 mg oral dose of psilocybin or a single 100 mg oral dose of niacin. Niacin will serve as an active placebo.

The purpose of this study is to evaluate the potential efficacy of a single 25 mg oral dose of psilocybin for MDD compared to the active placebo in otherwise medically-healthy participants, assessed as the difference between groups in changes in depressive symptoms from Baseline to Day 43 post-dose.

Detailed description: Major depressive disorder (MDD) has become a health crisis of epidemic proportions in the modern world. One in six individuals in the United States will experience an episode of major depression in his or her lifetime, and it is estimated that major depression will rank second after cardiac disease as a cause of international medical morbidity by the year 2020. Depression is associated with greater disability than are most other chronic illnesses and is a risk factor for mortality. Additionally, depression predicts the later development of a number of medical conditions, including cardiac and cerebrovascular disease, hypertension, diabetes, obesity, metabolic syndrome, dementia, and cancer. Unfortunately, most patients with depression do not experience a complete resolution of symptoms with antidepressant treatment. Partial-but incomplete-response to antidepressants is associated with an increased risk of full symptomatic relapse (even when on therapy) and a worse long-term disease course. Combined with the high prevalence and significant disability associated with MDD, the fact that currently available treatments are not fully adequate highlights the tremendous need to identify novel treatment strategies.

Data suggest that psilocybin may have behavioral effects relevant to the treatment of depression and recent studies also suggest that psilocybin may possess antidepressant properties. To further assess the effects of psilocybin on MDD signs and symptoms, this trial will enroll 100 participants, ages 21 to 65, who meet criteria for MDD. Participants will be stratified by study site and randomized with a 1-to-1 allocation under double-blind conditions to receive a single 25 mg oral dose of psilocybin or a single 100 mg oral dose of niacin. Niacin will serve as an active placebo.

To enhance participant safety, a Set and Setting (SaS) protocol will be utilized similar to the protocol that has been used in all modern studies of psilocybin. The SaS protocol for this study includes: 1) a period of preparation with session Facilitators prior to dosing; 2) administration of study medications in an aesthetically pleasing room under the supervision of two Facilitators who are present throughout the session; and 3) three post-dose integration sessions during which participants are encouraged to discuss their intervention experience with the Facilitators. The SaS protocol will be identical for those randomized to psilocybin or active placebo.

The primary objective of this study is to evaluate the potential efficacy of a single 25 mg oral dose of psilocybin for MDD compared to the active placebo (niacin), assessed as the difference between groups in changes in depressive symptoms from Baseline to Day 43 post-dose.

Eligibility criteria: Inclusion Criteria:

* 21 to 65 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
* Have an identified support person and agree to be accompanied home by that person following dosing
* Have sustained moderate-severe depression symptoms at Screening and Baseline
* Meet DSM-5 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

Exclusion Criteria:

* Women who are pregnant or who intend to become pregnant during the study or who are currently nursing
* Have any of the following cardiovascular conditions: uncontrolled hypertension, coronary artery disease, congenital long QT syndrome, cardiac hypertrophy, cardiac ischemia, congestive heart failure, myocardial infarction, tachycardia, artificial heart valve, a clinically significant screening ECG abnormality, or any other significant cardiovascular condition
* Have a history of stroke or Transient Ischemic Attack (TIA)
* Have moderate to severe hepatic impairment
* Have epilepsy
* Have insulin-dependent diabetes
* Have a positive urine drug test
* Nicotine dependence that would disallow an individual to be nicotine free for the 7-10 hours during the dosing period
* Meet DSM-5 criteria for schizophrenia spectrum or other psychotic disorders, including major depressive disorder with psychotic features, or Bipolar I or Bipolar II Disorder
* Meet DSM-5 criteria for antisocial personality disorder
* Meet DSM-5 criteria for a moderate or severe alcohol or drug use disorder

Primary outcomes:
measure: Change in central rater Montgomery-Asberg Depression Rating Scale (MADRS) total score from Baseline to post-dose Day 43
timeFrame: Baseline; Day 43 post-dose
Secondary outcomes:
measure: Change in central rater MADRS score from Baseline to post-dose Day 8
timeFrame: Baseline, Day 8 post-dose
measure: Change in on-site rater administered Sheehan Disability Scale (SDS) score from Baseline to post-dose Day 43
timeFrame: Day 8, 15, 29, and 43 post-dose
measure: Sustained depressive symptom response defined as a ≥ 50% reduction from Baseline central rater MADRS score at all post-dose assessments
timeFrame: Day 8, 15, 29, and 43 post-dose
measure: Sustained depressive symptom remission defined as a central rater MADRS total score ≤ 10 at all post-dose assessments
timeFrame: Day 8, 15, 29, and 43 post-dose
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Santa Monica
country: United States
facility: Pacific Neuroscience Institute
state: California
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Lauderhill
country: United States
facility: Segal Trials
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Chicago
country: United States
facility: Great Lakes Clinical Trials
state: Illinois
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Berlin
country: United States
facility: Hassman Research Institute
state: New Jersey
city: New York
country: United States
facility: New York University School of Medicine
state: New York
city: Draper
country: United States
facility: Cedar Clinical Research
state: Utah
city: Madison
country: United States
facility: University of Wisconsin - Madison
state: Wisconsin
Study officials:
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