Clinical trial NCT03356483: Efficacy of Psilocybin in OCD: a Double-Blind, Placebo-Controlled Study.
Official title: Psilocybin Treatment in Obsessive-Compulsive Disorder: a Preliminary Efficacy Study and Exploratory Investigation of Neural Correlates.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Obsessive-Compulsive Disorder
Keywords: Psilocybin
Lead sponsor: Yale University
Sponsor class: OTHER
Collaborators: name: Heffter Research Institute
name: National Institute of Mental Health (NIMH)
First posted: 2017-11-29
Enrollment: 31
Sex: ALL
Minimum age (years): 21
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: In the study, half of the participants will be randomized to receive psilocybin (n=15) or the active-placebo-control, niacin (n=15). Following the first treatment session of either the active agent or active-placebo-control, participants who were randomized to receive active-placebo-control will be offered the option to receive open-label psilocybin. The blind will be broken at 48-hours to make this determination.
Primary purpose: TREATMENT

Brief summary: This study aims to investigate the effects of oral psilocybin on OCD symptomatology and provide the first evidence of the neural mechanism that may mediate psilocybin's purported therapeutic effects on OCD.

Detailed description: Aim 1: To investigate the effects of psilocybin on OCD symptomatology. OCD symptom severity will be assessed before treatment and 24 and 48 hours after treatment, one week after treatment, two weeks, one month, and three months after treatment. Hypothesis: We hypothesize that 0.25mg/kg of psilocybin will lead to greater symptom improvement than niacin (as the active-placebo-control agent) at the primary endpoint of 48 hours post-dosing and at all other assessment points.

Aim 2: To explore the relationship between the psilocybin-induced brain connectivity changes and symptom change in OCD. Resting-state brain connectivity will be assessed before and 48 hours after treatment. Hypothesis: We hypothesize that (i) psilocybin will normalize abnormal fronto-striatal functional connectivity in patients with OCD; and (ii) normalization of these abnormalities will correlate with improvement in symptomatology after psilocybin treatment.

This study will pilot a single-center, randomized, active-placebo-controlled, double-blind design to examine the clinical and neural effects on OCD, of either 0.25mg/kg of psilocybin or active placebo-control agent (niacin 250mg), given along with non-drug preparatory and follow-up support appointments to 30 study participants. The duration of the randomized study phase is from consent until two weeks after drug administration. Participants will be followed for 12 weeks (3 months) post-study drug administration.

Eligible participants will be admitted as an inpatient for at least 3 nights / 4 days surrounding the initial drug administration (or more, at the option of the subject and the investigator). Participants will be randomized into active medication and active-placebo-control groups, and will be blinded as to their study condition. This admission 2 nights prior to the drug administration will allow the participant to adjust to sleeping on the unit and allow them to settle in to the research unit routine. A return for an fMRI scan (48 hours after the administration session) will be scheduled. The participants who received active-placebo-control will be offered the option to receive open-label psilocybin.

Eligibility criteria: Inclusion Criteria:

1. Primary DSM-5 diagnosis of OCD
2. Y-BOCS score of 19 or greater
3. Failure of at least one trial of standard care treatment (medication and/or psychotherapy \[CBT/ERP\]) for OCD
4. English proficiency and fluency, and ability to understand the consent process and provide written informed consent
5. Willingness to sign a medical release for direct communication between research staff and external provider(s) about the participant's treatment and medical histories
6. Non-consumption of SSRIs for at least 8 weeks at the time of randomization
7. Willingness to refrain from psychiatric medications (e.g., antidepressants, first- and second-generation antipsychotics, mood stabilizers) during the study period, as well as certain other medications (e.g., anti-seizure medications, cardiovascular medications, and aldomet specifically) during the day of dosing
8. Willingness to abstain from THC-containing products for study duration. A negative urinary drug screen is also required at baseline and the day of dosing.
9. A negative urinary pregnancy screen at study entry and day of dosing if of childbearing potential, and willingness to use adequate birth control for study duration
10. Having a contact person who is willing and able to be reached by the study team in the event of an emergency/crisis, and who is able to transport the participant home at the end of the inpatient stay/dosing week
11. Willingness to commit to all study procedures and visits, including inpatient stay, assessments and self-reports, neuroimaging, and being medically cleared to be discharged and transported home at the end of the dosing week

Exclusion Criteria:

1. Personal or immediate family history of schizophrenia spectrum and other psychotic disorders, bipolar I or II disorder, or major depressive disorder with psychotic features
2. Active suicidal intent
3. Unremitted Tourette syndrome
4. Autism spectrum disorder
5. OCPD or BPD
6. Current substance use disorder (except mild alcohol use disorder)
7. Unstable neurological or medical condition(s) that may render study procedures unsafe, including poorly managed diabetes, hypertension, or cardiovascular conditions, or history of seizure(s) or chronic/severe headaches
8. Any history of head injury with loss of consciousness for more than 30 minutes
9. Any contraindications to undergoing an MRI scan, including having metal implants or metal fragments in the body
10. Any use of psychedelic substances within the prior 12 months

Primary outcomes:
measure: Changes in severity of OCD symptoms, which will be measured by The Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). The Primary Outcome Measure will be collected at baseline and 48 hours, assessing change from baseline at 48 hours.
timeFrame: Baseline, 48 hours post-drug, weeks: 1, 2, 4, 12 post-drug
measure: Changes in severity of OCD symptoms, measured by Acute Yale-Brown Obsessive-Compulsive Scale (A-YBOCS)
timeFrame: Baseline, 24 hours post-drug, 48 hours post-drug
measure: Changes in severity of OCD symptoms, measured by Visual Analog Scale (VAS) for OCD symptoms
timeFrame: Baseline, 24 hours post-drug, 48 hours post-drug
measure: Changes in suicidality, measured by the Columbia-Suicide Severity Rating Scale (C-SSRS) Since Last Visit version
timeFrame: Up to 12 weeks post-drug
Secondary outcomes:
measure: Changes in brain connectivity, which will be measured with functional Magnetic Imaging Resonance (fMRI).
timeFrame: Baseline & 48 hours post-drug
measure: Changes in depression symptoms, which will be measured by The Montgomery-Asberg Depression Scale (MADRS).
timeFrame: Baseline, 2 days post-drug, weeks: 1, 2, 4, 12, post-drug
measure: Changes in depression symptoms, which will be measured by the Beck Depression Inventory (BDI).
timeFrame: Baseline, 1 day post-drug, weeks: 2 & 12 post-drug
measure: Changes in dysfunctional beliefs, which will be measured by The Obsessive Beliefs Questionnaire (OBQ-44).
timeFrame: Baseline & 2 weeks post-drug
measure: Changes in OCD symptoms, which will be measured by The Obsessive-Compulsive Inventory - Revised (OCI-R).
timeFrame: Baseline & 2 weeks post-drug
measure: Changes in OCD dimensions, which will be measured by The Obsessive-Compulsive Trait Core Dimensions Questionnaire (OC-TCDQ).
timeFrame: Baseline & 2 weeks post-drug
measure: Changes in anxiety, which will be measured by State-Trait Anxiety Inventory (STAI).
timeFrame: Baseline, 2 days post-drug, weeks: 1, 2, 4, 12 post-drug
measure: Changes in quality of life, which will be measured by The Quality of Life Enjoyment & Satisfaction Questionnaire (Q-LESQ-SF).
timeFrame: Baseline, weeks: 2 & 12 post-drug
measure: Changes in experiential aspects of psilocybin, which will be measured by The Mystical Experience Questionnaire (MEQ).
timeFrame: Day of drug administration, weeks: 2 & 12 post-drug
measure: Changes in meaning of life, which will be measured by The Schedule for Meaning in Life Evaluation (SMiLE).
timeFrame: Baseline, weeks: 1 & 12 post-drug
measure: Challenging Experience Questionnaire (CEQ)
timeFrame: Day of drug administration
measure: 5-Dimension - Altered States of Consciousness (5D-ASC)
timeFrame: Day of drug administration
measure: Changes in different dimensions of emotional experience, which will be measured by The Positive and Negative Affect Schedule Expanded Form (PANAS-X).
timeFrame: Baseline, 2 days post-drug, weeks: 1, 2, 4, 12 post-drug
measure: Changes of the effects of Psilocybin, which will be measured by The Persisting Effects Questionnaire (PEQ).
timeFrame: 2 days post-drug, weeks: 4 & 12 post-drug
measure: Changes in connection to nature, which will be measured by The Nature Relatedness Scale (NRS).
timeFrame: Baseline & 2 weeks post-drug
measure: Changes in opinion towards pro-environmental behavior, which will be measured by The Pro-Environmental Behavior Scale (PEBS).
timeFrame: Baseline & 2 weeks post-drug
measure: Changes in anthropomorphism, which will be measured by The Individual Differences in Anthropomorphism Questionnaire (IDAQ).
timeFrame: Baseline & 2 weeks post-drug
measure: Changes in beliefs of mind-body dualism, which will be measured by The Mind-Body Dualism Scale (MBDS).
timeFrame: Baseline & 2 weeks post-drug
measure: Change in interpersonal connectedness, which will be measured by The Inclusion of Others in Self Scale (IOS).
timeFrame: Baseline & 2 weeks post-drug
measure: Change in moral relativism and idealism, which will be measured by The Ethical Positions Questionnaire (EPQ).
timeFrame: Baseline & 2 weeks post-drug
measure: Changes in alcohol consumption, which will be measured by The Alcohol Use Disorders Identification Test (AUDIT).
timeFrame: Baseline & 12 weeks post-drug
measure: Changes in urgent care and emergency room use, which will be measured by The Utilization of Facility and Emergent Care (UFEC).
timeFrame: Baseline & 12 weeks post-drug
measure: Changes in drug-related problems, which will be measured by The Drug Use Disorders Identification Test (DUDIT).
timeFrame: Baseline & 12 weeks post-drug
measure: Changes in tobacco use, motivation to quit, and dependence, which will be measured by The Self-reported Nicotine Use (SRNU).
timeFrame: Baseline & 12 weeks post-drug
measure: Changes in sleep quality, which will be measured by The Pittsburgh Sleep Quality Index (PSQI).
timeFrame: Baseline, 48 hours post-drug, weeks: 4 & 12 post-drug
measure: Changes in readiness to change, which will be measured by The University of Rhode Island Change Assessment (URICA).
timeFrame: Baseline, 48 hours post-drug, weeks: 4, 8, 12 post-drug
measure: Changes in symptom severity and treatment response, which will be measured by The Clinical Global Impressions (CGI).
timeFrame: Baseline & 12 weeks post-drug
measure: Changes in functional impairment, which will be measured by The Sheehan Disability Scale (SDS).
timeFrame: Baseline & 12 weeks post-drug
measure: Changes in optimism and pessimism, which will be measured by The Life Orientation Test Revised (LOT-R).
timeFrame: Baseline & 12 weeks post-drug
measure: Changes in OCD symptoms, which will be measured by The Padua Inventory of OCD symptoms.
timeFrame: Baseline & 12 weeks post-drug
measure: Changes in action identification, measured by the Behavior Identification Form (BIF)
timeFrame: Baseline & 1 week post-drug
measure: Changes in reactions to research participation, measured by the Reactions to Research Participation Questionnaire (RRPQ)
timeFrame: 48 hours post-drug and 12 weeks post-drug
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Connecticut Mental Health Center
state: Connecticut
Study officials:
affiliation: Yale University
name: Benjamin Kelmendi, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Yale University
name: Christopher Pittenger, MD, PhD
role: STUDY_DIRECTOR
References:
citation: Moreno FA, Wiegand CB, Taitano EK, Delgado PL. Safety, tolerability, and efficacy of psilocybin in 9 patients with obsessive-compulsive disorder. J Clin Psychiatry. 2006 Nov;67(11):1735-40. doi: 10.4088/jcp.v67n1110.
citation: Ross S, Bossis A, Guss J, Agin-Liebes G, Malone T, Cohen B, Mennenga SE, Belser A, Kalliontzi K, Babb J, Su Z, Corby P, Schmidt BL. Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial. J Psychopharmacol. 2016 Dec;30(12):1165-1180. doi: 10.1177/0269881116675512.
citation: Griffiths RR, Johnson MW, Carducci MA, Umbricht A, Richards WA, Richards BD, Cosimano MP, Klinedinst MA. Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial. J Psychopharmacol. 2016 Dec;30(12):1181-1197. doi: 10.1177/0269881116675513.
citation: Carhart-Harris RL, Erritzoe D, Williams T, Stone JM, Reed LJ, Colasanti A, Tyacke RJ, Leech R, Malizia AL, Murphy K, Hobden P, Evans J, Feilding A, Wise RG, Nutt DJ. Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin. Proc Natl Acad Sci U S A. 2012 Feb 7;109(6):2138-43. doi: 10.1073/pnas.1119598109. Epub 2012 Jan 23.