The Effects of Psilocybin on Self-Focus and Self-Related Processing in Treatment Resistant MDD

NCT05381974 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: 2021P000863
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This open-label fMRI study will assess the effects of a single dose of psilocybin on rumination and the neural correlates of rumination in individuals with treatment-resistant major depressive disorder.

Conditions

Treatment-Resistant Major Depressive Disorder

Keywords

Psilocybin; Neuroimaging; Rumination; Treatment-Resistant Depression

Outcome Measures

Primary Outcomes (4)

• Change in Massachusetts General Hospital Rumination Questionnaire (MGH-RQ)

  A transdiagnostic state measure of rumination over the previous two weeks consisting of 9 items on a 5 point Likert scale from 0 (Never/Rarely) to 4 (All The Time).

  Baseline, and 3 weeks, 6 weeks, 9 weeks, and 12 weeks after psilocybin administration.

• Change in Resting-State Functional Connectivity

  Changes in resting-state activity during functional magnetic resonance imaging(fMRI) scans.

  Baseline, day of psilocybin administration, and 3 weeks, and 12 weeks after psilocybin administration.

• Change in Self-Attribution Task performance

  Participants are shown words one at a time and asked to answer if each of the words apply to 'Self' or 'Other'

  Baseline, day of psilocybin administration, and 3 weeks, and 12 weeks after psilocybin administration.

• Change in Task-Based Activity during Self-Attribution Task

  Changes in task-based activity during functional magnetic resonance imaging(fMRI) scans.

  Baseline, day of psilocybin administration, and 3 weeks, and 12 weeks after psilocybin administration.

Secondary Outcomes (12)

• Change in Montgomery-Asberg Depression Rating Scale(MADRS)

  Baseline, the day before psilocybin administration and at 1 day, 1 week, 2 weeks, 3 weeks, 6 weeks, 9 weeks and 12 weeks after psilocybin administration.

• Change in Quick Inventory of Depressive Symptomatology - 16 item (QIDSR-SR-16)

  Baseline, the day before psilocybin administration and at 1 day, 1 week, 2 weeks, 3 weeks, 6 weeks, 9 weeks and 12 weeks after psilocybin administration.

• Change in Positive and Negative Affect Schedule (PANAS)

  Baseline, the day of psilocybin administration and at 3 weeks and 12 weeks after psilocybin administration.

• Change in Hamilton Depression Rating Scale - 17 item (HAM-D-17)

  Baseline and 3 weeks and 12 weeks after psilocybin administration.

• Change in Ruminative Response Scale (RRS)

  Baseline and 12 weeks after psilocybin administration.

Other Outcomes (6)

• Change in Social Adjustment Scale-Self-Report - Short Version (SAS-SR: Short)

  Baseline and 2 weeks, 3 weeks, and 12 weeks after psilocybin administration.

• Change in UCLA Loneliness Scale

  Baseline and 2 weeks, 3 weeks, and 12 weeks after psilocybin administration.

• Change in Brief Fear of Negative Evaluation Scale - Second Version (BFNE-II)

  Baseline and 2 weeks, 3 weeks, and 12 weeks after psilocybin administration.

Study Arms (1)

Psilocybin

EXPERIMENTAL

25mg of Psilocybin

Drug: Psilocybin

Interventions

Psilocybin DRUG

Open-Label

Psilocybin

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Must be able to sign the informed consent form (ICF).
• Be 18-55 years of age at screening.
• At least moderate MDD based on clinical assessment and a structured clinical interview, the Mini International Neuropsychiatric Interview Version 7.02 (MINI).
• Hamilton Depression Rating Scale - 17 item (HAM-D-17) score ≥ 18 at Screening and at Baseline.
• Failure to respond to an adequate dose and duration of 2, 3, or 4 pharmacological treatments for the current episode as determined through the Massachusetts General Hospital Antidepressant Treatment History Response Questionnaire (MGH-ATRQ) and using the supplementary advice on additional antidepressants not included in MGH-ATRQ. Augmentation with an add-on treatment counts as a second treatment, provided it is approved for the adjunctive treatment of MDD.
• McLean Screening Instrument for Borderline Personality Disorder (MSI-BPD) \< 7 at Screening.
• Have successfully discontinued all antidepressant medications at least 2 weeks prior to Baseline Scan. (Please note: once enrolled in the study, participants will have to successfully undergo a taper off of all psychotropic medications under the supervision of a study psychiatrist and in coordination with their treatment team).
• A score \> 40 on the Wechsler Test of Adult Reading.
• Be right-handed as determined by the Edinburg Handedness Inventory.
• Ability to complete all protocol required assessment tools without any assistance or alteration to the copyrighted assessments, and to comply with all study visits.
• Have ongoing established mental health care.

You may not qualify if:

• Current, past history, or family history, of schizophrenia, psychotic disorder (unless substance induced or due to a medical condition), bipolar disorder, delusional disorder, paranoid personality disorder, schizoaffective disorder, borderline personality disorder, or any serious psychiatric comorbidity as assessed by medical history and a structured clinical interview (version 7.0.2 MINI).
• Positive MR screen (e.g., metal implant, claustrophobia, etc).
• Prior electroconvulsive therapy and/or ketamine for current episode.
• Current cognitive behavioral therapy (CBT) that will not remain stable for the duration of the study. CBT cannot be initiated within 21 days of Baseline.
• Current (within the last year) alcohol or substance abuse as informed by DSM-5 at Screening.
• Significant suicide risk as defined by (1) suicidal ideation as endorsed on items 4 or 5 on the Columbia-Suicide Severity Rating Scale (C-SSRS) within the past year, at Screening or at Baseline, or; (2) suicidal behaviors within the past year, or; (3) clinical assessment of significant suicidal risk during clinical interview.
• Significant homicide risk as defined by clinical interview.
• Depression secondary to other severe medical conditions.
• Currently taking benzodiazepines daily.
• Other personal circumstances and behavior judged to be incompatible with establishment of rapport or safe exposure to psilocybin, as well as exposure to psilocybin or other psychedelics within one year of screening.
• Women who are pregnant, nursing, or planning a pregnancy. Participants who are sexually active must agree to use a highly effective contraceptive method throughout their participation in the study. Women of childbearing potential must have a negative urine pregnancy test at Screening and Day Before Psilocybin.
• Cardiovascular conditions: recent stroke (\< 1 year from signing of consent), recent myocardial infarction (\< 1 year from signing of ICF), hypertension (blood pressure \> 140/90 mmHg) or QTc \> 450 msec) or clinically significant arrhythmia within 1 year of signing the ICF, current anticoagulant therapy, aneurysmal disease.
• Uncontrolled insulin dependent diabetes.
• Seizure disorder.
• Positive urine drug screen for illicit drugs or drugs of abuse (to include but not limited to opiates, PCP, cocaine, amphetamines, methamphetamines, benzodiazepines, barbiturates, and cannabis) at Screening and Day Before Psilocybin. Any positive urine drug test will be reviewed with participants to determine the pattern of use and eligibility will be determined at the investigator's discretion.

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• COMPASS Pathways: collaborator

Study Sites (1)

Athinoula A. Martinos Center for Biomedical Imaging

Charlestown, Massachusetts, 02129, United States

Location

MeSH Terms

Conditions

Rumination Syndrome; Depressive Disorder, Treatment-Resistant

Interventions

Psilocybin

Condition Hierarchy (Ancestors)

Gastrointestinal Diseases; Digestive System Diseases; Feeding and Eating Disorders; Mental Disorders; Depressive Disorder; Mood Disorders

Intervention Hierarchy (Ancestors)

Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Tryptamines; Indolizidines; Indolizines

Study Officials

• Sharmin Ghaznavi, MD, PhD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Psychiatrist

Study Record Dates

• First Submitted: May 10, 2022
• First Posted: May 19, 2022
• Study Start: September 15, 2022
• Primary Completion: June 1, 2023
• Study Completion: June 1, 2023
• Last Updated: January 24, 2024

Record last verified: 2024-01

Locations

US (1)