Clinical trial NCT06303739: Psilocybin-Assisted Therapy in Treatment-Resistant Depression
Official title: Induction Protocol for Psilocybin-Assisted Therapy in Treatment-Resistant Depression (TRD): A Pilot Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Refractory Depression
Treatment Resistant Depression
Keywords: psilocybin
psychedelic
refractory depression
psychedelic-assisted therapy
treatment-resistant depression
TRD
depression
Lead sponsor: University of North Carolina, Chapel Hill
Sponsor class: OTHER
Collaborators: name: Foundation of Hope, North Carolina
First posted: 2024-03-12
Enrollment: 20
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: Participants are randomized into one of two groups and will receive either one single treatment of psilocybin-assisted therapy with follow-up therapy and assessments or two treatments spaced two weeks apart with follow-up therapy and assessments.
Primary purpose: TREATMENT

Brief summary: The goal of this clinical trial is to test how well psilocybin-assisted therapy works in treating people with depression. The main questions this study aims to answer are:

* Does psilocybin with assisted therapy help improve symptoms for people with depression?
* How long do the effects of this treatment last?

Participants will:

* Take part in a couple of screening and preparation visits.
* Be given psilocybin in one or two treatment sessions.
* Attend a series of follow-up sessions over the following year.
* Complete forms and surveys to test how their symptoms have changed and what they thought of their experience.

Researchers will also compare whether one treatment or two treatments help improve symptoms more for participants.

Detailed description: Major depressive disorder (MDD) ranks fourth in global disease burden and has significant morbidity, mortality, societal and financial costs. However, few adequate and effective treatments exist with 60% of MDD patients not responding sufficiently to an initial oral antidepressant treatment. These patients who experience treatment resistant depression (TRD), defined as an intolerance or lack of response to two antidepressants of different classes, have limited treatment options beyond the antidepressant treatments that often yield insufficient results or relapse. Psilocybin, a novel treatment, has been found to relieve symptoms of TRD, but there are limited studies on specific dosing and long term treatment follow-up. In this study, the investigators will look closer at the effectiveness of one treatment with psilocybin versus two treatments with psilocybin, as well as the long term effectiveness over the first 12 months after treatment.

Eligibility criteria: Inclusion Criteria:

* Provision of signed and dated informed consent form.
* Willingness to comply with all study procedures and availability for the study.
* Diagnostic and Statistical Manual of Mental Disorders 5 (DSM-V) diagnosis of major depressive disorder.
* Currently experiencing a major depressive episode, lasting at least 3 months
* Failure to respond or inability to tolerate at least 2 guideline-concordant pharmacological treatments from different pharmacologic classes during the current major depressive episode
* Good health evidenced by medical history and routine lab tests
* No central nervous system (CNS) or neurocognitive impairment
* Ability to take oral medication and to follow to the psilocybin-assisted therapy protocol
* Identified support person to accompany patient home after dosing
* Use of effective contraception throughout the study by those with child-bearing potential
* Use of condoms or other effective contraceptive methods by males with reproductive potential
* Fully vaccinated and up to date on vaccination against COVID-19, as defined by Center for Disease Control guidelines
* Following Lifestyle Considerations throughout study (no nicotine containing products in clinical unit, refrain from operating heavy machinery for the duration of treatment day, no more than two servings 8 hours prior to treatment, no psychoactive drugs 72 hours before treatment, refrain from consuming foods that would interfere with drug absorption, minimize interaction with household immunocompromised contacts)

Exclusion Criteria:

* Family history (first- or second-degree relatives) or diagnosis of bipolar disorder with psychotic features, schizophrenia, schizoaffective disorder, hallucinogen-induced psychosis, anti-social personality disorder, or other psychotic disorder.
* Borderline personality disorder, defined by DSM-V criteria, that in the judgement of the Investigator is likely to complicate the assessment of clinical response to study treatments or limits the patient's ability to comply with study procedures.
* Alcohol or other substance use disorder (except tobacco/nicotine) that has been active within the 6 months prior to enrollment.
* Recent use (within past 6 months) of esketamine, ketamine or classic hallucinogens (psilocybin-containing mushrooms or LSD) or use of psychedelics more than 10 times in lifetime.
* Participants with active suicidal ideation or plan with a Columbia Suicide Severity Rating Scale (C-SSRS) score greater than or equal to 4.
* Current active self-injurious behavior, requiring medical attention or per investigator discretion.
* Diagnosis of Obsessive-compulsive disorder or post-traumatic stress disorder.
* Within 72 hours of psilocybin administration, use of nicotine, alcohol, or other controlled substances.
* Current delirium, dementia, amnestic disorder, or other cognitive disorders.
* Any current or past medical or neurological illness (including chronic pain syndromes and/or history of cerebrovascular event (excluding migraine)) that, in the opinion of the investigator, may confound the interpretation of study assessments
* Known allergic reactions to components of psilocybin.
* Medically instability at screening, including hepatic, renal, circulatory, cardiac (arrhythmia, uncontrolled hypertension, systolic BP \> 140 mmHg or diastolic BP \> 90 mmHg, abnormal QTc), pulmonary or CNS (seizure disorder or treatment with antiepileptic drugs) impairment.
* Current pregnancy or lactation.
* Febrile illness in last 3 weeks.
* Current use or use within 4 weeks of psilocybin administration of Monoamine oxidase inhibitors (MAOIs), alcohol dehydrogenase inhibitors and antipsychotics (concomitant medications will be allowed per investigator discretion).
* Current treatment with buproprion greater than 300mg/day.
* Current use of tramadol.
* Prior participation in psilocybin-assisted therapy trial and or regular use of hallucinogens
* Treatment with another investigational drug or other intervention during study period.

Primary outcomes:
measure: Change in HAM-D-17 Scores between Baseline and 2 Weeks after Treatment
timeFrame: Baseline, 2 weeks
measure: Change in QIDS SR-16 Scores between Baseline and 2 Weeks after Treatment
timeFrame: Baseline, 2 weeks
measure: Number of Participants Achieving Remission 2 Weeks after Treatment
timeFrame: up to 2 weeks
measure: Number of Participants Achieving Response 2 weeks after treatment
timeFrame: up to 2 weeks
Secondary outcomes:
measure: Number of Participants Achieving Remission at 6 Weeks
timeFrame: up to 6 weeks
measure: Number of Participants Achieving Response at 6 Weeks
timeFrame: up to 6 weeks
measure: Number of Participants Achieving Remission at 3 Months
timeFrame: up to 3 months
measure: Number of Participants Achieving Response at 3 Months
timeFrame: up to 3 months
measure: Number of Participants Achieving Remission at 6 Months
timeFrame: up to 6 months
measure: Number of Participants Achieving Response at 6 Months
timeFrame: up to 6 months
measure: Number of Participants Achieving Remission at 9 Months
timeFrame: up to 9 months
measure: Number of Participants Achieving Response at 9 Months
timeFrame: up to 9 months
measure: Number of Participants Achieving Remission at 12 Months
timeFrame: up to 12 months
measure: Number of Participants Achieving Response at 12 Months
timeFrame: up to 12 months
measure: Time to Relapse in Participants Who Showed Remission at 2 weeks
timeFrame: up to 1 year after treatment
measure: Time to Relapse in Participants Who Showed Response at 2 Weeks
timeFrame: up to 1 year after treatment
measure: Change in HAM-D-17 Scores between Baseline and 6 Weeks after Treatment
timeFrame: Baseline, 6 weeks
measure: Change in HAM-D-17 Scores between Baseline and 3 Months after Treatment
timeFrame: Baseline, 3 Months
measure: Change in HAM-D-17 Scores between Baseline and 6 Months after Treatment
timeFrame: Baseline, 6 Months
measure: Change in HAM-D-17 Scores between Baseline and 9 Months after Treatment
timeFrame: Baseline, 9 Months
measure: Change in HAM-D-17 Scores between Baseline and 12 Months after Treatment
timeFrame: Baseline, 12 months
measure: Change in QIDS SR-16 Scores between Baseline and 6 Weeks after Treatment
timeFrame: Baseline, 6 weeks
measure: Change in QIDS SR-16 Scores between Baseline and 3 Months after Treatment
timeFrame: Baseline, 3 Months
measure: Change in QIDS SR-16 Scores between Baseline and 6 Months after Treatment
timeFrame: Baseline, 6 Months
measure: Change in QIDS SR-16 Scores between Baseline and 9 Months after Treatment
timeFrame: Baseline, 9 Months
measure: Change in QIDS SR-16 Scores between Baseline and 12 Months after Treatment
timeFrame: Baseline, 12 Months
Other outcomes:
Locations:
city: Chapel Hill
country: United States
facility: UNC Chapel Hill Medical Center
state: North Carolina
Study officials:
affiliation: Director of Interventional Psychiatry
name: Robert K McClure, MD
role: PRINCIPAL_INVESTIGATOR
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