Pilot RECAP Study in Healthy Volunteers

NCT ID: NCT04842045

Last Updated: 2023-05-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 8 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-05-21
• Study Completion Date: 2022-11-17

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.

Detailed Description

The PILOT RECAP Study will investigate the effect of co- administering the amnestic agent midazolam with a single 25 mg dose of psilocybin on the induction of a psychedelic experience and subsequent memory for the experience with the goal of identifying an optimal dosing regimen of midazolam that will allow a psychedelic experience to occur while also inducing amnesia for the experience. Identifying this midazolam dosing regimen will allow us in a subsequent stage of the RECAP program to test whether memory for the psychedelic experience is required/important for psilocybin to produce longer-term antidepressant effects. This is a phase 1 study in psychiatrically and medically healthy volunteers. Given this, there is no disease background for PILOT RECAP per se. However, the purpose of PILOT RECAP is to identify an optimal midazolam dosing schedule to be used in a subsequent study (RECAP) in patients with major depressive disorder (MDD).

The investigational treatment for PILOT RECAP is a single 25 mg dose of psilocybin combined with repeated intravenous (IV) boluses of midazolam dosed at levels known to maintain conscious experience while inducing subsequent amnesia for the experience upon its conclusion. Because PILOT RECAP is the first study to examine this drug combination, no data are currently available on this approach. Psilocybin + midazolam will be administered within a "Set and Setting" (SaS) protocol that provides psychoeducation and therapeutic support prior to, during, and following psychedelic dosing, and that has been standard procedure for recent studies of psilocybin in humans. It is believed that this SaS approach enhances clinical efficacy and safety. SaS is an integral component of the PILOT RECAP intervention.

The PILOT RECAP study will not enroll vulnerable populations. During this study, participants are asked to:

• Refrain from use of psychotropic medications. Use of such medications prior to psilocybin/midazolam dosing will result in a participant being discontinued from the study.
• Refrain from use of any illegal psychoactive substances from screening until study termination.
• Refrain from using legal psychoactive substance for the following defined time periods (the exception is caffeine):

• Tobacco and Nicotine: from screening until study termination
• Alcohol: 72 hours prior to the Dosing Visit

Conditions

Psychedelic Experiences; Amnesia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Single Arm

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.

Group Type: EXPERIMENTAL

Psilocybin and Midazolam

Intervention Type: 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.

Interventions

Psilocybin and Midazolam

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.

Intervention Type: DRUG

Other Intervention Names

Psilocybine; Psilocibin; benzodiazepine

Eligibility Criteria

Inclusion Criteria

• Age 21 to 65 years at screening
• Medically healthy (does not meet criteria for an exclusionary medical condition)
• 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

Exclusion Criteria

• Pregnancy
• Current exclusionary medical illness
• 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

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of Wisconsin, Madison

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Christopher R Nicholas, MD,PHD

Role: PRINCIPAL_INVESTIGATOR

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

Locations

UWHealth, 600 Highland Avenue

Madison, Wisconsin, United States

Countries

United States

Other Identifiers

A532017

Identifier Type: OTHER

Identifier Source: secondary_id

SMPH/FAMILY MEDICINE

Identifier Type: OTHER

Identifier Source: secondary_id

AAH3816

Identifier Type: OTHER

Identifier Source: secondary_id

PROTOCOL V7.0 10 OCT 2021

Identifier Type: OTHER

Identifier Source: secondary_id

2020-0085

Identifier Type: -

Identifier Source: org_study_id