Clinical trial NCT03300947: Psilocybin for Treatment of Obsessive Compulsive Disorder
Official title: Psilocybin for Treatment of Obsessive Compulsive Disorder
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Obsessive-compulsive Disorder (OCD)
Lead sponsor: University of Arizona
Sponsor class: OTHER
First posted: 2017-10-04
Enrollment: 15
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: All participants will be randomly assigned to administration of low dose (100 µg/kg) psilocybin, High dose (300 µg/kg) psilocybin, or Lorazepam (1 mg). Eight different sessions divided in two phases will ensure all subjects are exposed to psilocybin at some point during the study in a blinded fashion.
Primary purpose: TREATMENT

Brief summary: This study will evaluate whether psilocybin, a hallucinogenic drug, improves symptoms of obsessive compulsive disorder (OCD), whether it is safely tolerated as treatment of OCD, and will investigate the mechanisms by which it works.

Detailed description: The study seeks to improve our ability to treat and improve the lives of people who have obsessive-compulsive disorder (OCD) by exploring the benefits of psilocybin, a mind-altering drug that changes activity in brain areas believed to be involved in OCD. Anecdotal reports and results from previous research support this idea. This two-phase study will enroll patients with symptomatic OCD who are not taking mind-altering medications or street drugs.

During Phase One, neither participants nor the investigators will know which drugs or doses are administered. This information will be available if it is medically necessary to reveal which drugs and doses were administered. Five subjects in each group will receive study drug a total of four times, separated by one week. During Phase Two, participants will not know which drugs or doses they receive, but the investigators will know. All participants will receive psilocybin at some point during study participation.

Participants will be randomly assigned to one of the following groups:

1. Low dose (100 µg/kg) psilocybin,
2. High dose (300 µg/kg) psilocybin, or
3. Lorazepam (1 mg), a calming medication. Lorazepam is used often for anxiety and will be used to mask which drug participants receive.

Participants will spend approximately 12 hours at the research site under observation during each visit, until they are free of the mind-altering effects of the drug and are determined by the psychiatrist to be safe to go home accompanied by a responsible adult. The effects of low versus high doses, and the additive effects of repeated doses will be analyzed and will be compared to the effects of lorazepam.

Eligibility criteria: Inclusion Criteria:

* Have moderate to severe OCD (DSM-5) after diagnostic interview using the Structured Clinical Interview for DSM-5 Research Version (SCID-R).
* Failed at least one adequate attempted routine care treatment.
* Considered safe for independent living

Exclusion Criteria:

* Concurrent psychosis, active substance use disorder, or a personal history of psychosis.
* Medical illness based on physical examination and routine blood testing that may complicate cardiovascular safety or drug metabolism or excretion, such as uncontrolled hypertension, severe cardiac disease, or kidney or liver failure.
* Unstable Chronic Obstructive Pulmonary Disease (COPD) or severe sleep apnea
* Psychiatric comorbidity that may represent an acute risk to their own or others' safety.
* Subjects may not be using antidepressant medication for OCD for at least two weeks before receiving study drug, and they cannot require any sedative, narcotic, or neuroleptic medications on a regular basis. Any of these medications they have taken should have been stopped long enough in the past to allow for their elimination and safe withdrawal prior to starting administration of the study drug. The specific time required will be dependent on the medication the patient was previously receiving.
* Women who are pregnant, breastfeeding, or unwilling/unable to practice medically acceptable birth control during the study.
* Allergy to lorazepam.

Primary outcomes:
measure: Treatment-phase effects on Obsessive-Compulsive symptom severity
timeFrame: weekly Y-BOCS rating prior to ingestion of study drug on Week 1 through 8, and week 9 (follow up week 1)
Secondary outcomes:
measure: Acute Incidence of Treatment Emergent Adverse Events
timeFrame: At 0, and 24 hours after blinded medication ingestion
measure: Duration of Effects on Obsessive-Compulsive symptom severity
timeFrame: Follow-up assessments will be conducted weekly over the phone weekly (± 3 days) for one month after last dose, monthly (± 7 days) for three months beginning 28 days after last dose, and then once at 6 months after last dose (± 7 days).
measure: Long Term Incidence and Duration of Treatment Emergent Psychiatric Adverse Events
timeFrame: Follow-up assessments will be conducted weekly over the phone (± 3 days) for one month after last dose, monthly (± 7 days) for three months beginning 28 days after last dose, and then once at 6 months after last dose (± 7 days).
measure: Changes in the magnitude of Error Related Negativity (an electroencephalographic biomarker of OCD) assessed by Error-related negativity (voltage) and mid-frontal theta power (time-frequency approach)
timeFrame: Baseline, and 9-10 hours after ingestion of study dose 1, 4, and 8.
measure: Prospective Self-Assessment of Depression Symptoms
timeFrame: Baseline, 24 hours after each dose during 8 week active phase, and during the follow-up phase (weekly for one month after last dose, monthly for three months beginning 28 days after last dose, and then once at 6 months after last dose.
measure: Prospective Clinician-Rated Assessment of Depression Symptoms
timeFrame: Baseline, 4 weeks, 8 weeks, and during the follow-up phase (weekly for one month after last dose, monthly for three months beginning 28 days after last dose, and then once at 6 months after last dose
measure: Changes in functional connectivity: 1) between the Caudate Nucleus (CN) and Orbital Frontal Cortex (OFC); 2) within the default mode network (DMN).
timeFrame: Imaging at baseline, and 9-10 hours post ingestion on weeks 1, 4, and 8. YBOCS at baseline and 8 hours after ingestion at weeks 1, 4, and 8.
Other outcomes:
Locations:
city: Tucson
country: United States
facility: University of Arizona
state: Arizona
Study officials:
affiliation: Professor of Psychiatry and Associate Vice President, Diversity and Inclusion
name: Francisco A. Moreno, MD
role: PRINCIPAL_INVESTIGATOR
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.