Adjunctive Effects of Psilocybin and a Formulation of Buprenorphine

• ClinicalTrials.gov Identifier: NCT04161066
• Recruitment Status: Recruiting
• First Posted: November 13, 2019
• Last Update Posted: December 27, 2023
• Sponsor: University of Wisconsin, Madison
• Collaborators: Heffter Research Institute; Etheridge Foundation
• Information provided by (Responsible Party): University of Wisconsin, Madison

Tracking Information

• First Submitted Date: August 22, 2019
• First Posted Date: November 13, 2019
• Last Update Posted Date: December 27, 2023
• Actual Study Start Date: January 13, 2021
• Estimated Primary Completion Date: June 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 20, 2023)

• Safety Measured by Incidence and Severity of Adverse Events 24 hrs post-dose [ Time Frame: approximately Week 1 ]
  In participants with OUD, the safety of this intervention will be assessed by characterize adverse events associated with adding two psilocybin doses to a stable buprenorphine regimen.
• Safety Measured by Incidence and Severity of Adverse Events 24 hrs post-dose [ Time Frame: approximately Week 5 ]
  In participants with OUD, the safety of this intervention will be assessed by characterizing adverse events associated with adding two psilocybin doses to a stable buprenorphine-naloxone regimen.
• Mean Change in Symptoms of Opioid Withdrawal Measured by COWS Instrument [ Time Frame: up to 5 weeks ]
  It is hypothesized that co-administration of oral psilocybin with a buprenorphine-naloxone formulation will not cause signs and symptoms of opioid withdrawal. This will be measured by the Clinical Opiate Withdrawal Scale (COWS) instrument, an 11-item scale administered by the clinician where total score of: 5- 12 = mild withdrawal; 13-24 = moderate withdrawal; 25-36 = moderately severe withdrawal; and more than 36 = severe withdrawal. Administered before the dose and again 8 hours after the dose.
• Mean Change in Peripheral Capillary Oxygen [ Time Frame: up to 5 weeks ]
  It is hypothesized that co-administration of oral psilocybin with a buprenorphine-naloxone formulation will not cause opioid intoxication. Opioid intoxication will be determined by drops peripheral capillary oxygen saturation (SpO2) before and after dosing.
• Mean Change in ECG [ Time Frame: up to 5 weeks ]
  It is hypothesized that co-administration of oral psilocybin with a buprenorphine-naloxone formulation will not cause a clinically significant increase in the QTc interval. The QTc interval will be measured by electrocardiogram (ECG) before and after dosing. If a QTc(F), calculated by the CardioCard system exceeds 470msec, a study physician will be contacted immediately for further monitoring and treatment recommendations.

Original Primary Outcome Measures (submitted: November 8, 2019)

• Safety Measured by Incidence and Severity of Adverse Events 24 hrs post-dose [ Time Frame: approximately Week 1 ]
  In participants with OUD in early or sustained full recovery on buprenorphine/naloxone therapy, the safety of this intervention will be assessed by characterize adverse events associated with adding two psilocybin doses to a stable buprenorphine/naloxone regimen.
• Safety Measured by Incidence and Severity of Adverse Events 24 hrs post-dose [ Time Frame: approximately Week 5 ]
  In participants with OUD in early or sustained full recovery on buprenorphine/naloxone therapy, the safety of this intervention will be assessed by characterize adverse events associated with adding two psilocybin doses to a stable buprenorphine/naloxone regimen.
• Mean Change in Symptoms of Opioid Withdrawal Measured by COWS Instrument [ Time Frame: up to 5 weeks ]
  It is hypothesized that co-administration of oral psilocybin with buprenorphine/naloxone will not cause signs and symptoms of opioid withdrawal. This will be measured by the Clinical Opiate Withdrawal Scale (COWS) instrument, an 11-item scale administered by the clinician where total score of: 5- 12 = mild withdrawal; 13-24 = moderate withdrawal; 25-36 = moderately severe withdrawal; and more than 36 = severe withdrawal. Administered before the dose and again 8 hours after the dose.
• Mean Change in Peripheral Capillary Oxygen [ Time Frame: up to 5 weeks ]
  It is hypothesized that co-administration of oral psilocybin with buprenorphine/naloxone will not cause opioid intoxication. Opioid intoxication will be determined by drops peripheral capillary oxygen saturation (SpO2) before and after dosing.
• Mean Change in ECG [ Time Frame: up to 5 weeks ]
  It is hypothesized that co-administration of oral psilocybin with buprenorphine/naloxone will not cause a clinically significant increase in the QTc interval. The QTc interval will be measured by electrocardiogram (ECG) before and after dosing. ECGs will be collected using the CardioCard PC computer-based system, once before the dose, and again at 1, 2, 3, 4, 6, and 8 hours after the dose. If a QTc(F), calculated by the CardioCard system exceeds 470msec, a study physician will be contacted immediately for further monitoring and treatment recommendations.

Current Secondary Outcome Measures (submitted: February 20, 2023)

• Change in Opioid Craving Scale (OCS) from baseline through end of study [ Time Frame: Baseline, Week 1, Week 5, and Week 9 ]
  To evaluate the effect of psilocybin treatment on the effectiveness of buprenorphine-naloxone maintenance therapy. The hypothesis is that co-administration of oral psilocybin with a buprenorphine-naloxone formulation will not cause an increase in opioid craving, as measured by the OCS at baseline, week 1, week 5, and week 9. The OCS is a 3-item visual analog scale to measure the frequency and intensity of opioid craving. Total score ranges from 0-30 where the higher the number, the higher the craving.
• Mean Number of Days of Participant Opioid Use via Time Line Follow Back (TLFB) [ Time Frame: up to 9 weeks ]
  It is hypothesized that co-administration of oral psilocybin with a buprenorphine-naloxone formulation will not be associated with an increase in self-reported illicit opioid use. This will be measured by Time Line Follow-Back calendar method for up to the 28 days following the last dosing session. Participants will be asked to recall the previous 28 days of substance use at the first in-person visit.

Original Secondary Outcome Measures (submitted: November 8, 2019)

• Change in Opioid Craving Scale (OCS) from baseline through end of study [ Time Frame: Baseline, Week 1, Week 5, and Week 9 ]
  To evaluate the effect of psilocybin treatment on the effectiveness of buprenorphine/naloxone maintenance therapy. The hypothesis is that co-administration of oral psilocybin with buprenorphine/naloxone will not cause an increase in opioid craving, as measured by the OCS at baseline, week 1, week 5, and week 9. The OCS is a 3-item visual analog scale to measure the frequency and intensity of opioid craving. Total score ranges from 0-30 where the higher the number, the higher the craving.
• Mystical Effects Questionnaire (MEQ) after each dose [ Time Frame: approximately Week 1 and Week 5 ]
  To evaluate the effect of concurrent buprenorphine/naloxone use on the effects of psilocybin therapy. The hypothesis is that co-administration of buprenorphine/naloxone with oral psilocybin will not be associated with a change in the effects of psilocybin, as measured by adverse events (Primary Outcome Measure), and the MEQ. The MEQ is a 30-item assessment used to characterize the consciousness-altering effects of psilocybin. Total possible range of scores is 0-150 where the higher the number the higher the consciousness-altering effects.
• Mean Number of Days of Participant Opioid Use via Time Line Follow Back (TLFB) [ Time Frame: up to 9 weeks ]
  It is hypothesized that co-administration of oral psilocybin with buprenorphine/naloxone will not be associated with an increase in self-reported illicit opioid use. This will be measured by Time Line Follow-Back calendar method for up to the 28 days following the last dosing session. Participants will be asked to recall the previous 28 days of substance use at the first in-person visit.

• Current Other Pre-specified Outcome Measures: Not Provided

Original Other Pre-specified Outcome Measures (submitted: November 8, 2019)

• Change in Participant Generalized Self-Efficacy Scale (GSES) [ Time Frame: Baseline and End of Study, Up to 9 weeks ]
  Descriptive changes in participant self-efficacy, quality of life, and pain will be explored through a number of participant surveys. The GSES is a 10-item scale to assess a participants self-beliefs to cope with difficult situations. The total range of possible scores is 10-40, higher scores indicate more self-efficacy.
• Change in The Meaning in Life Questionnaire (TMQ) [ Time Frame: Baseline and End of Study, Up to 9 weeks ]
  Descriptive changes in participant self-efficacy, quality of life, and pain will be explored through a number of participant surveys. TMQ is a 10-item questionnaire designed to measure how much participants feel their lives have meaning and how much they strive to find meaning and understanding in their lives. Items are scored on a 7-point Likert Scale from 1 (absolutely true) to 7 (absolutely untrue). Item 9 is reverse scored. The total range of possible scores is 10-70, higher scores indicate more perceived meaning in life.
• Change in The Gratitude Questionnaire (TGQ) [ Time Frame: Baseline and End of Study, Up to 9 weeks ]
  Descriptive changes in participant self-efficacy, quality of life, and pain will be explored through a number of participant surveys. TGQ is a 6-item questionnaire measures levels of dispositional gratitude. Items are scored on a 7-point Likert Scale from 1 (strongly disagree) to 7 (strongly agree). Items 3 and 6 are reverse scored. The total range of possible scores is 6-42, higher scores indicate more gratitude.
• Change in Brief Pain Inventory (BPI) [ Time Frame: Baseline and End of Study, Up to 9 weeks ]
  Descriptive changes in participant self-efficacy, quality of life, and pain will be explored through a number of participant surveys. BPI is a 9-item questionnaire designed to rapidly assess the severity of pain and its impact on functioning. Higher scores (0-10) indicate higher perceived pain.

Descriptive Information

• Brief Title: Adjunctive Effects of Psilocybin and a Formulation of Buprenorphine
• Official Title: Phase I Study of the Safety and Adjunctive Effects of Psilocybin in Adults With Opioid Use Disorder Maintained on a Buprenorphine/Naloxone Formulation

Brief Summary

Primary Aim: In participants with OUD, to characterize adverse events associated with adding two psilocybin doses to a stable buprenorphine-naloxone formulation.

Secondary Aim: To evaluate the effect of psilocybin treatment on the effectiveness of a buprenorphine-naloxone maintenance therapy.

Secondary Aim: To evaluate the effect of concurrent buprenorphine-naloxone use on the effects of psilocybin therapy.

Descriptive Aim: To describe any changes in self-efficacy, quality of life, pain.

Detailed Description

The primary objective of this clinical trial is to determine the safety of psilocybin in adult patients with opioid use disorder concurrently taking buprenorphine-naloxone.

Eligible participants will be adults with active opioid use disorder (OUD) who are willing to begin and maintain a daily dose of buprenorphine-naloxone throughout study participation. Initiation, stabilization, and maintenance of buprenorphine-naloxone will be overseen by a qualified study medical provider. After psychological screening and at least 6 hours of preparatory counseling and preparation for the psilocybin dosing, set, and setting, each participant will ingest 1 oral dose of psilocybin. All dosing sessions will be attended by 2 specially trained facilitators, in a dedicated Clinical Research Facility. After eight hours of observation in the dosing room, the participant will be kept overnight in the hospital Clinical Research Unit, and complete an integration session with a psychologist before discharge to home. Approximately 4 weeks after the first dose, the participant will receive a second oral dose of psilocybin, with the same length of observation.

Participants who have been administered the first dose but decline to receive the second dose will remain evaluable. At study termination, their active study participation will end, but completion of the 28 day post-dose follow up will be requested.

The primary endpoint is the assessment of the safety of concurrent administration of a buprenorphine-naloxone formulation and psilocybin as determined by physiological measures (ECG, respiratory rate, blood pressure, body temperature, and blood oxygen saturation) and validated clinical and self-report measures (Clinical Opiate Withdrawal Scale (COWS), Opioid Craving Scale (OCS), Timeline Follow-Back (TLFB)).

If you are interested in participating in this study, please fill out a brief 1-minute survey at the link in the "More Information" section at the bottom of this record.

• Study Type: Interventional
• Study Phase: Phase 1

Study Design

Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:

open-label pilot study

Masking: None (Open Label)
Primary Purpose: Health Services Research

• Condition: Opioid Use Disorder

Intervention

Drug: Psilocybin with facilitated counseling

open-label pilot study

Study Arms

Experimental: Open-label

Psilocybin with facilitated counseling: Psilocybin will be administered in the form of capsules, taken orally with water. Each participant will receive 2 doses, approximately 4 weeks apart.

Intervention: Drug: Psilocybin with facilitated counseling

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: November 8, 2019): 10
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: June 2024
• Estimated Primary Completion Date: June 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Aged 21 to 65 years
• Able to read, speak, and understand spoken and written English
• Diagnosis of moderate or severe opioid use disorder (OUD)

• Current opioid misuse, with misuse occurring on at least 10 of the last 30 days. Misuse will be defined as either:

  1. Use of illicit opioids, such as heroin or non-prescribed fentanyl; or use of an outpatient prescription opioid (such as oxycodone, morphine, or hydrocodone) through a route other than FDA approved (e.g. nasal, injected), and/or
  2. Use of a prescription opioid via a route (e.g. nasal, injected, chewed) or for a purpose (e.g. intoxication, anxiety relief) other than that for which it was prescribed.
• Able to achieve stable daily dose of a buprenorphine-naloxone formulation that controls opioid withdrawal symptoms
• Persons of childbearing potential must agree to practice an effective means of contraception throughout their participation in the study, beginning at screening and throughout follow-up
• Ability and willingness to adhere to study requirements, including attending all study visits, preparatory and follow-up sessions, and evaluations
• Healthy kidney function
• Able to provide contact information for a local support person. This person must be available during both 24-hour treatment and observation periods, and willing to provide the participant social/emotional support the day after each treatment and as needed during the dosing day and/or overnight observation period.

Exclusion Criteria:

• Currently prescribed and has taken buprenorphine or buprenorphine formulation (e.g., Suboxone®) for over four weeks immediately prior to initial study contact
• Currently receiving pharmacotherapy of any duration with methadone
• Current participation in a drug treatment court program or other legal supervision. Individuals who are under legal supervision will be advised that participating in this study could potentially violate terms of probation, parole, or extended supervision. Contact information for the individual's community supervision officer must be collected to confirm whether study participation may impact the potential participant's status on probation or parole
• Inadequately treated hypertension
• Current acute coronary syndrome or angina
• Evidence of ischemic disease, cardiac conduction defects, and/or ventricular arrhythmias on screening ECG
• History of heart transplant
• Current insulin dependence, due to Type I or Type II diabetes
• Urine drug test containing non-prescribed drugs of abuse
• Any finding(s), based on the screening process, that the PI feels makes the study unsuitable for the participant

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 21 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: David Horton, MS; 608-444-2397; protea.research@mailplus.wisc.edu

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04161066
• Other Study ID Numbers: 2019-0187; A532007 ( Other Identifier: UW Madison ); SMPH/FAMILY MEDICINE ( Other Identifier: UW Madison ); Protocol Version 9/22/2023 ( Other Identifier: UW Madison )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No
• Plan Description: No individual participant data sharing is planned

• Current Responsible Party: University of Wisconsin, Madison
• Original Responsible Party: Same as current
• Current Study Sponsor: University of Wisconsin, Madison
• Original Study Sponsor: Same as current

Collaborators

• Heffter Research Institute
• Etheridge Foundation

Investigators

• Principal Investigator: Randall Brown, MD PhD; University of Wisconsin, Madison

• PRS Account: University of Wisconsin, Madison
• Verification Date: July 2023