Pilot RECAP Study in Healthy Volunteers

NCT04842045 | Completed Phase 1 DMC FDA Drug

• 5 other identifiers: 2020-0085A532017SMPH/FAMILY MEDICINEAAH3816PROTOCOL V7.0 10 OCT 2021
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective of the RECAP Study Program is to investigate the role played by conscious experience in the antidepressant effects of the psychedelic agent psilocybin. This pilot dosing study (PILOT RECAP) is designed to determine the optimal dose of midazolam that allows a psychedelic experience to occur while inducing amnesia for the experience. This is an essential step required for subsequent evaluation of the role of memory for the psychedelic experience in the antidepressant effects of psilocybin in the full RECAP study.

Conditions

Psychedelic Experiences; Amnesia

Keywords

Memory; Amnesia; Healthy Volunteer

Outcome Measures

Primary Outcomes (2)

• Number of participants scoring >50 percent of normative scores on selected questions from the Altered States of Consciousness (ASC) questionnaire asked during the dosing session Day 0.

  Participants will complete a selection of several questions from the ASC questionnaire that strongly associate positively or negatively with later antidepressant effect of psilocybin in patients with treatment resistant depression or capture classic features of the psychedelic experience. During the dosing session, investigator will repeatedly ask selected items from the ASC scale to get a "real time" measure of what the participants are experiencing. Each of these items will be scored separately. Higher score are indicative of a more intense psychedelic experience.

  On Day 14

• Number of participants scoring < 50 percent on post-dosing Day 1 of the mean normative score of ASC data from healthy volunteers administered the ASC questionnaire post-dosing

  To assess the degree to which midazolam has induced amnesia for the psychedelic experience, participants will complete the full ASC. The ASC is a 94 item questionaire. In response to each item, participants are asked to mark their experience somewhere between 'No, not more than usual' to 'Yes, much more than usual'. Normal waking consciousness corresponds to a mark at the very left end of the scale, i.e. 'No, Not more than usual'. Responses marked more towards right side of the range are considered high on psychedelic experience.

  On Day 15

Secondary Outcomes (7)

• Accuracy on post-dosing Day 1 in recognizing ASC items asked during the dosing session Day 0 (number of correct versus distractor items)

  On Day 15

• Safety of psilocybin-midazolam co-administration assessed by number of adverse event incidences in each severity grade.

  up to 4 weeks

• Safety of psilocybin-midazolam co-administration assessed by number of participants requiring medical attention due to adverse events

  up to 4 weeks

• Safety of psilocybin-midazolam co-administration assessed by number of participants requiring psychiatric attention due to adverse events

  up to 4 weeks

• Safety of psilocybin-midazolam co-administration assessed by number of participants leading to withdrawal from study due to adverse events

  up to 4 weeks

Study Arms (1)

Single Arm

EXPERIMENTAL

Medically and psychiatrically healthy adults ages 21 to 65 years will receive a single 25 mg dose of psilocybin combined with repeated boluses of midazolam administered in a clinically supportive setting.

Drug: Psilocybin and Midazolam

Interventions

Psilocybin and Midazolam DRUG

The psilocybin used in this study is synthetically manufactured in a laboratory and meets quality specifications suitable for human research use. The active drug is encapsulated using a hydroxypropyl methylcellulose (HPMC) capsule and contains 25 mg of psilocybin. The midazolam in this study will be administered intravenously. The total dose administered to a given subject is dependent on the individual's level of amnesia, sedation scale score, age, and weight.

Also known as: Psilocybine, Psilocibin, benzodiazepine

Single Arm

Eligibility Criteria

• Age: 21 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 21 to 65 years at screening
• No current DSM-5 psychiatric diagnosis
• No current use of psychotropic medications
• Ability/willingness to complete all study activities
• Use of acceptable contraceptive methods (sexually active males and women of childbearing potential)
• Speaks and reads English
• No use of psychedelic drugs within prior 3 months of dosing visit
• Able to swallow oral medications

You may not qualify if:

• Pregnancy
• Current DSM-5 psychiatric diagnosis and/or suicidal thoughts/behavior within prior 12 months
• Clinically significant safety lab abnormalities (i.e., Complete Blood Count with Differential, Comprehensive Metabolic Panel, and urinalysis)
• Clinically significant electrocardiogram (ECG)
• Hypertension or tachycardia
• First degree relative(s) with a history of schizophrenia, schizophreniform disorder, bipolar I disorder, bipolar II disorder, major depressive disorder with psychotic features

Sponsors & Collaborators

• University of Wisconsin, Madison: lead

Study Sites (1)

UWHealth, 600 Highland Avenue

Madison, Wisconsin, 53792, United States

Location

MeSH Terms

Conditions

Amnesia

Interventions

Psilocybin; Midazolam; Benzodiazepines

Condition Hierarchy (Ancestors)

Memory Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

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

Study Officials

• Christopher R Nicholas, MD,PHD

  University of Wisconsin Hospital and Clinics, Madison, Wisconsin, United State, 53715

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Open trial of a single 25 mg dose of psilocybin combined with repeated boluses of midazolam in medically and psychiatrically healthy volunteers.

Study Record Dates

• First Submitted: April 1, 2021
• First Posted: April 12, 2021
• Study Start: May 21, 2021
• Primary Completion: November 17, 2022
• Study Completion: November 17, 2022
• Last Updated: May 19, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)