Clinical trial NCT05370911: Effects of Repeated Psilocybin Dosing in OCD
Official title: Effects of Repeated Dosing of Psilocybin on Obsessive-Compulsive Disorder: A Randomized, Waitlist-Controlled Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Obsessive-Compulsive Disorder
Keywords: Psilocybin
Lead sponsor: Yale University
Sponsor class: OTHER
Collaborators: name: Steven & Alexandra Cohen Foundation
First posted: 2022-05-12
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: In the study, participants will be randomized to receive either immediate treatment with two doses of oral psilocybin separated by one week (n = 15) or enter a waitlist control/delayed treatment group and receive the same treatment 7 weeks post-randomization (n = 15).
Primary purpose: TREATMENT

Brief summary: This study aims to investigate the effects of repeated dosing of oral psilocybin on obsessive-compulsive disorder (OCD) symptomatology in a randomized, waitlist-controlled design with blinded independent ratings, and assess psychological mechanisms that may mediate psilocybin's therapeutic effects on OCD.

Detailed description: Aim 1: To examine the effects of two doses of psilocybin on OCD symptoms among participants in the immediate treatment condition, compared to participants in the waitlist control/delayed treatment condition. The investigators hypothesize that participants in the immediate treatment group will report statistically significantly greater symptom improvement from baseline 4 days post-second dose, compared to participants in the waitlist control/delayed treatment group at the same interval during their waitlist phase.

Aim 2: To examine the effects of two doses of psilocybin on OCD symptoms, compared to one dose. The investigators hypothesize that two doses of oral psilocybin will reduce OCD symptoms to a statistically significantly greater extent than one dose.

This study aims to investigate the effects of repeated dosing of oral psilocybin on OCD symptomatology and assess psychological mechanisms that may mediate psilocybin's therapeutic effects on OCD. This study will employ a randomized, waitlist-controlled design with blinded independent ratings, with participants randomized to receive either immediate treatment (two doses oral psilocybin separated by one week) or delayed treatment (7 weeks post-randomization). An adaptive dose selection strategy will be implemented, with the first dose being standardized at 25 mg of psilocybin, and the second dose being either the same or a higher dosage (i.e., 30 mg) on the basis of a clinically significant response from baseline or not, respectively, 4 days post-first dose.

This study is conducted entirely on an outpatient basis with the possibility of remote/virtual follow-up visits after each dosing session. The dosing sessions last the entire day, and participants will be medically cleared prior to being permitted to return home with assistance (e.g., driven by a family member or friend, or ride share).

Eligibility criteria: Inclusion Criteria:

1. Primary DSM-5 diagnosis of OCD, with Y-BOCS-II score of 26 or greater at screening
2. Failed at least one medication and/or therapy trial of standard care treatment for OCD
3. English fluency
4. Agree to sign a medical release for investigators to communicate directly with participants' providers to confirm medication and psychotherapy histories or arrange contingencies in event of crises.
5. Agree to provide an adult contact (relative, spouse, close friend or other caregiver) who is willing and able to be reached by the PI and/or study personnel in the event of an emergency, and who can provide transportation for study visits and independently comment on any changes in the participant's mood or behavior after each administration of psilocybin.
6. Agree to commit to all study procedures.
7. Ability to orally ingest pills for psilocybin dosing visits.
8. Agree to adhere to lifestyle and medication modifications.
9. Must not be on psychotropic medications for OCD or comorbid psychiatric conditions for at least 8 weeks at the time of randomization, and agree to refrain from taking or starting any psychiatric medications until after 4 weeks post-second dose.
10. Must not be in current psychotherapy (CBT or ERP) and must not start new course of psychotherapy (CBT or ERP) for OCD or comorbid psychiatric conditions until after 4 weeks post-second dose.
11. If participant is of childbearing potential, must have a negative pregnancy test at study entry and prior to each dosing session.
12. If participant is of childbearing potential, agree to use adequate birth control and not attempt to become pregnant during study up to 4 weeks post-second dose.

Exclusion Criteria:

1. Personal or immediate (first-degree relative) family history of formally diagnosed schizophrenia or other psychotic disorders, or bipolar I/II disorder
2. Lack of knowledge about biological families' medical history, due to adoption or other circumstance
3. Active suicidal intent or suicidal or non-suicidal self-injurious behaviors
4. Unremitted Tourette syndrome
5. Lifetime diagnosis of autism spectrum disorder
6. Current substance use disorder (except for mild alcohol use disorder)
7. Any neurological condition, including history of seizure(s) or chronic/severe headaches
8. Any history of head injury with loss of consciousness for more than 30 min
9. Any use of classic psychedelic substances within the prior 12 months
10. Unwillingness to abstain from use of classic psychedelics outside of the study up to 4 weeks post-second dose.
11. Use of tobacco products or a THC-containing product more than 2 times per week on average over the past 30 days at screening.
12. Unwilingness or inability to abstain from use of tobacco or THC-containing products from 1 week prior to randomization up to 4 weeks post-second dose.
13. Positive urine drug test for any prohibited substance at screening or days of dosing, or positive breathalyzer test for alcohol on days of dosing
14. Unwillingness or inability to abstain from alcohol use at least 24 hours prior to the days of dosing, up to 24 hours after each dosing day (or corresponding intervals for waitlist group).
15. Any medical conditions that may render study procedures unsafe, including hypertension, history of cardiovascular disease, moderate-to-severe hepatic or renal impairment, diabetes, and hypo- or hyperthyroidism.

Primary outcomes:
measure: Change in Yale-Brown Obsessive-Compulsive Scale-Second Edition (Y-BOCS-II) Severity Scale total score from baseline at 4 days post-second dose
timeFrame: Baseline & 4 days post-second dose
Secondary outcomes:
measure: Change in Montgomery-Asberg Depression Scale (MADRS) total score from baseline at 4 days post-second dose
timeFrame: Baseline & 4 days post-second dose
measure: Change in Dimensional Obsessive-Compulsive Scale (DOCS) total score from baseline at 4 days post-second dose
timeFrame: Baseline & 4 days post-second dose
measure: Change in Obsessive Beliefs Questionnaire-44 (OBQ-44) total score from baseline at 4 days post-second dose
timeFrame: Baseline & 4 days post-second dose
measure: Change in Acceptance and Action Questionnaire for Obsessions and Compulsions (AAQ-OC) total score from baseline at 4 days post-second dose
timeFrame: Baseline & 4 days post-second dose
measure: Change in Tolerance of Uncontrollability Questionnaire (TOUQ) total score from baseline at 4 days post-second dose
timeFrame: Baseline & 4 days post-second dose
measure: Change in White Bear Suppression Inventory (WBSI) total score from baseline at 4 days post-second dose
timeFrame: Baseline & 4 days post-second dose
measure: Change in Difficulties in Emotion Regulation Scale (DERS) total score from baseline at 4 days post-second dose
timeFrame: Baseline & 4 days post-second dose
measure: Change in Southampton Mindfulness Questionnaire (SMQ) total score from baseline at 4 days post-second dose
timeFrame: Baseline & 4 days post-second dose
measure: Toronto Mindfulness Scale (TMS)
timeFrame: Up to 3 weeks for immediate treatment condition, and up to 10 weeks for waitlist condition
measure: Set, Setting, and Intentions (SSI) Scale
timeFrame: Up to 3 weeks for immediate treatment condition, and up to 10 weeks for waitlist condition
measure: Mystical Experience Questionnaire (MEQ)
timeFrame: Up to 3 weeks for immediate treatment condition, and up to 10 weeks for waitlist condition
measure: Psychological Insight Questionnaire (PIQ)
timeFrame: Up to 3 weeks for immediate treatment condition, and up to 10 weeks for waitlist condition
measure: Challenging Experience Questionnaire (CEQ)
timeFrame: Up to 3 weeks for immediate treatment condition, and up to 10 weeks for waitlist condition
measure: Ego Dissolution Inventory (EDI)
timeFrame: Up to 3 weeks for immediate treatment condition, and up to 10 weeks for waitlist condition
measure: Emotional Breakthrough Inventory (EBI)
timeFrame: Up to 3 weeks for immediate treatment condition, and up to 10 weeks for waitlist condition
measure: Change in Self-Compassion Scale (SCS) total mean score from baseline at 4 days post-second dose
timeFrame: Baseline & 4 days post-second dose
measure: Change in Ten-Item Personality Inventory (TIPI) total score from baseline at 4 days post-second dose
timeFrame: Screening, 4 days and 12 months post-second dose
measure: Change in Persisting Effects Questionnaire (PEQ) subscale scores from 4 weeks post-second dose at 12 months post-second dose
timeFrame: 4 weeks post-second dose & 12 months post-second dose
measure: Change in Alcohol Use Disorders Identification Test (AUDIT) total score from baseline at 4 weeks post-second dose
timeFrame: Baseline & 4 weeks post-second dose
measure: Change in Drug Use Disorders Identification Test (DUDIT) total score from baseline at 4 weeks post-second dose
timeFrame: Baseline & 4 weeks post-second dose
measure: Change in Fagerstrom Test for Nicotine Dependence (FTND) total score from baseline at 4 weeks post-second dose
timeFrame: Baseline & 4 weeks post-second dose
measure: Change in World Health Organization Disability Assessment Scale, v2.0 (WHODAS-2.0) 12-item, self-administered version total score from baseline at 4 days post-second dose
timeFrame: Baseline & 4 weeks post-second dose
measure: Change in Quality of Life Enjoyment & Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) percentage maximum score from baseline at 4 days post-second dose
timeFrame: Baseline & 4 weeks post-second dose
measure: Writing task
timeFrame: Baseline & 4 days post-second dose
measure: Columbia Suicide Severity and Risk Scale (C-SSRS) Since Last Visit version
timeFrame: Every study visit through study completion, an average of 12 months and 3 weeks for immediate treatment condition, and an average of 12 months and 10 weeks for waitlist condition
measure: Theoretical Orientation Profile Scale-Revised (TOPS-R)
timeFrame: Baseline
measure: Working Alliance Inventory-Short Revised (WAI-SR)
timeFrame: Up to 4 days post-second dose
measure: Change in Symptom Provocation Task (SPT) ratings from baseline at 4 days post-second dose
timeFrame: Baseline & 4 days post-second dose
measure: Stanford Expectations of Treatment Scale (SETS)
timeFrame: Baseline
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Yale OCD Research Clinic (40 Temple St, 4th Floor)
state: Connecticut
Study officials:
affiliation: Yale University
name: Benjamin Kelmendi, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Yale University
name: Terence Ching, PhD
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: Davis AK, Barrett FS, May DG, Cosimano MP, Sepeda ND, Johnson MW, Finan PH, Griffiths RR. Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder: A Randomized Clinical Trial. JAMA Psychiatry. 2021 May 1;78(5):481-489. doi: 10.1001/jamapsychiatry.2020.3285.
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.