Treatment-Resistant Major Depressive DisorderPhase 2NCT05381974
The Effects of Psilocybin on Self-Focus and Self-Related Processing in Treatment Resistant MDD
A Phase 2 study testing Psilocybin in people with Treatment-Resistant Major Depressive Disorder, run by Massachusetts General Hospital at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Treatment-Resistant Major Depressive Disorder
- What is being tested?
- Psilocybin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Sep 2022to 1 Jun 2023
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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.
Show all 11Show fewer
- 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.
Who cannot join
- 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.
Show all 19Show fewer
- 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.
- Lifetime history of surgical procedures involving the brain or meninges, encephalitis, meningitis, degenerative central nervous system (CNS) disorder (e.g., Alzheimer's or Parkinson's Disease), epilepsy, mental retardation, or any other disease/procedure/accident/intervention which, according to the screening clinician, is deemed associated with significant injury to or malfunction of the CNS, or history of significant head trauma within the past 2 years.
- Any current or past history of any physical condition which in the investigator's opinion might put the subject at risk or interfere with study results interpretation.
- Current enrollment in any investigational drug or device study or participation in such within 6 months of Screening.
- Current enrollment in an interventional study for depression or participation in such within 6 months of Screening Visit.
Trial locations and contacts
1 site in 1 country.
United States1 site
Athinoula A. Martinos Center for Biomedical Imaging
Charlestown, Massachusetts, 02129
About this study
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.
- Being tested
- Psilocybin
- Keywords
- Psilocybin, Neuroimaging, Rumination, Treatment-Resistant Depression
- Medical subject headings
- Rumination Syndrome, Depressive Disorder, Treatment-Resistant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PsilocybinDrug
Open-Label
| Study group | Role | What they receive |
|---|---|---|
| Psilocybin | Experimental | 25mg of Psilocybin Receives: Drug: Psilocybin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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.
Measured: 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'
Measured: 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.
Measured: 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)
The MADRS is a clinician-rated scale measuring depression severity, consisting of 10 items, each scored from 0 (normal) to 6 (severe), for a total possible score of 60; higher scores denote greater severity.
Measured: 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)
The 16-item QIDS-SR-16 a self-rated scale designed to assess the severity of depressive symptoms in the nine diagnostic symptom domains of a major depressive episodes, exclusive of atypical or melancholic symptoms. The QIDS-SR-16 is sensitive to change with various treatments, demonstrating its utility in research settings. The total score ranges from 0 to 27 with 0 representing no depression and 27 representing severe depression.
Measured: 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)
The PANAS measures the acute emotional drug effects and comprises 2 mood scales that measure positive and negative affect. Participants respond to 20 items using a 5-point scale that ranges from "slightly or not at all (1)" to "extremely (5)". A total higher score on the positive affect questions indicates more of a positive affect while a lower score on the negative affect questions indicates less of a negative affect.
Measured: 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)
The HAM-D-17 is a 17 item scale used to assess the degree of symptom severity in depressed patients.
Measured: Baseline and 3 weeks and 12 weeks after psilocybin administration.
Change in Ruminative Response Scale (RRS)
A self-report measure of describing one's responses to depressed mood, consists of 22 items and three factors (Depression, Brooding, and Reflection). Each item is rated on a 4-point Likert scale ranging from 1 (never) to 4 (always). The total score ranges from 22 to 88, with higher scores indicating higher tendency to ruminate, i.e. higher trait rumination.
Measured: Baseline and 12 weeks after psilocybin administration.
Change in Rumination Reflection Questionnaire (RRQ)
The RRQ measures the extent to which a person tends to ruminate or engage in self-reflection. It consists of 24 items measured on a 5 point Likert scale from 1 (Strongly Disagree) to 5 (Strongly Agree),12 items which assess the tendency to ruminate, and 12 items which assess the tendency to engage in self reflection.
Measured: Baseline and 12 weeks after psilocybin administration.
Change in Penn State Worry Questionnaire (PSWQ)
The PSWQ is a 16-item questionnaire that aims to measure the trait of worry, using Likert rating from 1 (not at all typical of me) to 5 (very typical of me). The PSWQ attempts to measure the excessiveness, generality, and uncontrollable dimensions of worry.
Measured: Baseline and 12 weeks after psilocybin administration.
Change in NEO-Five-Factor Inventory (NEO-FFI)
The NEO-FFI is a 60-item psychological personality inventory that assesses based on the five- factor model: Openness to Experience, Conscientiousness, Extraversion, Agreeableness, and Neuroticism. Participants are asked to select the response that best represents their opinion on a 5-point scale: 0-Strongly Agree, 1-Agree, 2-Neutral, 3-Disagree, 4-Strongly Disagree.
Measured: Baseline and 12 weeks after psilocybin administration.
Change in Behavior Rating Inventory of Executive Function - Adult Version (BRIEF)
The BRIEF is a 75-item scale designed to assess executive function and self-regulation. Participants choose how often certain behaviors were problematic over the past month N-never, S-sometimes, O-often.
Measured: Baseline and 12 weeks after psilocybin administration.
Change in Cognitive Flexibility Inventory (CFI)
The CFI is a brief self-report measure of the type of cognitive flexibility necessary for individuals to successfully challenge and replace maladaptive thoughts with more balanced and adaptive thinking. The measure consists of 20 items and participants indicate the extent to which they agree or disagree with the statements in the items, on a scale from 1-Strongly Disagree to 7-Strongly Agree.
Measured: Baseline and 12 weeks after psilocybin administration.
Change in Emotional Faces Flanker Task
This task examines executive functioning as it assesses the ability to ignore/inhibit irrelevant flanking information in order to respond to the central task.
Measured: Baseline, day of psilocybin administration, and 3 weeks and 12 weeks after psilocybin administration.
Change in Depression Implicit Attitudes Task (IAT)
The IAT provides a measure of the strength of association between four categories by pairing two concept categories (e.g., Me/Not-Me) with two attribution categories (e.g., Happy/Sad).
Measured: Baseline, day of psilocybin administration, and 3 weeks and 12 weeks after psilocybin administration.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 May 2022
- Study start15 Sep 2022
- Primary completion1 Jun 2023
- Study completion1 Jun 2023
Why it stopped: Study was terminated due to difficulty recruiting patients who met inclusion/exclusion criteria. No participants received the intervention.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Treatment-Resistant Major Depressive DisorderStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- COMPASS Pathways
- Responsible party
- Principal investigator, Sharmin Ghaznavi, Massachusetts General Hospital
- Investigators
- Sharmin Ghaznavi, MD, PhD, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05381974
- Sponsor's protocol ID
- 2021P000863
- Status last verified
- Jan 2024
- First submitted
- 10 May 2022
- Last updated
- 24 Jan 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effects of Psilocybin on Self-Focus and Self-Related Processing in Treatment Resistant MDD
- ClinicalTrials.gov ID
- NCT05381974
- Acronym / sponsor ID
- 2021P000863
- Keywords
- Psilocybin, Neuroimaging, Rumination, Treatment-Resistant Depression
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Study was terminated due to difficulty recruiting patients who met inclusion/exclusion criteria. No participants received the intervention.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Collaborators
- COMPASS Pathways
- Study start
- 15 Sep 2022 (actual)
- Primary completion
- 1 Jun 2023 (actual)
- Study completion
- 1 Jun 2023 (actual)
- First posted
- 19 May 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Psilocybin | Experimental | Drug: Psilocybin25mg of Psilocybin |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (11 listed)
- 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.
Key exclusion criteria (19 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PsilocybinOpen-Label | Drug | Psilocybin |
Primary outcome
Change in Massachusetts General Hospital Rumination Questionnaire (MGH-RQ)
Time frame: Baseline, and 3 weeks, 6 weeks, 9 weeks, and 12 weeks after psilocybin administration.
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).
Change in Resting-State Functional Connectivity
Time frame: Baseline, day of psilocybin administration, and 3 weeks, and 12 weeks after psilocybin administration.
Changes in resting-state activity during functional magnetic resonance imaging(fMRI) scans.
Change in Self-Attribution Task performance
Time frame: Baseline, day of psilocybin administration, and 3 weeks, and 12 weeks after psilocybin administration.
Participants are shown words one at a time and asked to answer if each of the words apply to 'Self' or 'Other'
Change in Task-Based Activity during Self-Attribution Task
Time frame: Baseline, day of psilocybin administration, and 3 weeks, and 12 weeks after psilocybin administration.
Changes in task-based activity during functional magnetic resonance imaging(fMRI) scans.
12 secondary outcomes
Change in Montgomery-Asberg Depression Rating Scale(MADRS)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: Baseline and 3 weeks and 12 weeks after psilocybin administration.
Change in Ruminative Response Scale (RRS)
Time frame: Baseline and 12 weeks after psilocybin administration.
Change in Rumination Reflection Questionnaire (RRQ)
Time frame: Baseline and 12 weeks after psilocybin administration.
Change in Penn State Worry Questionnaire (PSWQ)
Time frame: Baseline and 12 weeks after psilocybin administration.
Change in NEO-Five-Factor Inventory (NEO-FFI)
Time frame: Baseline and 12 weeks after psilocybin administration.
Change in Behavior Rating Inventory of Executive Function - Adult Version (BRIEF)
Time frame: Baseline and 12 weeks after psilocybin administration.
Change in Cognitive Flexibility Inventory (CFI)
Time frame: Baseline and 12 weeks after psilocybin administration.
Change in Emotional Faces Flanker Task
Time frame: Baseline, day of psilocybin administration, and 3 weeks and 12 weeks after psilocybin administration.
Change in Depression Implicit Attitudes Task (IAT)
Time frame: Baseline, day of psilocybin administration, and 3 weeks and 12 weeks after psilocybin administration.
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jan 2024.
Related trials for Treatment-Resistant Major Depressive Disorder
RecruitingPhase 4
Biomarker-Guided Antidepressant Selection
Depression - Major Depressive Disorder, Treatment-resistant Depression (TRD)
RecruitingPhase 2
ACP-211 Monotherapy for Major Depressive Disorder With Inadequate Antidepressant Response
Major Depressive Disorder (MDD), Depressive Disorder, Treatment-Resistant
Active, not recruiting
rTMS to Target Neural Connectivity and Rumination in Treatment-Resistant Depression
Depression, Treatment Resistant
Recruiting
EEG-Guided Transcranial Magnetic Stimulation for Adults With Depression
Major Depressive Disorder (MDD), Treatment Resistant Depression
RecruitingObservational study
Natural History of Depression, Bipolar Disorder and Suicide Risk
Behavioral Symptoms, Suicide
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sharmin Ghaznavi, MD, PhD principal investigator
Massachusetts General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Psilocybin in people with Treatment-Resistant Major Depressive Disorder, run by Massachusetts General Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 24 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Massachusetts General Hospital Rumination Questionnaire (MGH-RQ) (time frame: Baseline, and 3 weeks, 6 weeks, 9 weeks, and 12 weeks after psilocybin administration.). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jan 2024.