Behavioral Pharmacological Examination of a Novel Buprenorphine Induction Method Among Individuals Who Use Fentanyl

NCT06089707 | Recruiting Phase 3 FDA Drug

• 1 other identifier: IRB00392041
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

The opioid overdose epidemic has persisted for several decades and is now further complicated by the permeation of fentanyl into the illicit opioid supply. While the effectiveness of medications to treat opioid use disorder (MOUD) have been well documented in the literature, the addition of fentanyl to the drug supply has complicated the initiation of MOUD, especially buprenorphine. Naloxone, an opioid antagonist, is currently utilized to reverse opioid overdose by displacing less-competitive ligands which bind at the mu-opioid receptor. Because induction to buprenorphine in the age of fentanyl is uncomfortable and can take several days to stabilize a patient on a therapeutic dose, the use of naloxone prior to buprenorphine can aid in a safe and rapid transition to buprenorphine treatment, without the effect of unintended prolonged precipitated withdrawal which can occur following the displacement of fentanyl by buprenorphine on the mu-opioid receptor. Therefore, this project will assess feasibility and acceptability of naloxone-facilitated buprenorphine initiation using a single-ascending dose design. The investigators will examine whether a single dose of buprenorphine is tolerated following administration of naloxone among a small group of individuals. If the dose is tolerated, the investigators will administer a larger dose among another small group of individuals. The investigators will examine the tolerability of up to 4 doses of buprenorphine following naloxone. This buprenorphine induction method has been characterized in case studies but it has not been evaluated in an empirical, systematic way in a controlled setting. This study will take place within an residential facility at Johns Hopkins Bayview Medical Campus, and will have immediate, real-world applicability in establishing a rapid, safe, and effective option to transition people with chronic fentanyl use to buprenorphine treatment.

Conditions

Opioid Use Disorder

Keywords

buprenorphine; fentanyl; initiation to treatment

Outcome Measures

Primary Outcomes (3)

• Peak opioid withdrawal as assessed by the Subjective Opiate Withdrawal Scale (SOWS)

  Opioid withdrawal severity will be measured with the Subjective Opiate Withdrawal Scale (SOWS) and will be computed as the peak total SOWS score in the 8 hours after buprenorphine administration. The SOWS consists of 16 opioid withdrawal symptoms that are assessed for severity on a scale from 0-4 ("Not at all" to "Extremely"). Total scores range from 0-64 where a score between 0-10 is considered mild, between 11-20 is considered moderate, and greater than 21 is considered severe.

  After administration of first dose of buprenorphine up to 8 hours

• Self-report acceptability

  Acceptability will be measured by an acceptability questionnaire designed by the research team. Items from the questionnaire will be computed as the average acceptability score. Scores range from 0-10, where 0 reflects no acceptability and 10 reflects high acceptability.

  3 days

• Length of time (hours) for participants to reach 8mg of buprenorphine

  Time between initial buprenorphine dose and time reaching a dose of at least 8mg buprenorphine dosage will be measured to understand how long it takes patients to tolerably receive the minimum maintenance dose of 8mg

  After initial buprenorphine dose up to 24 hours

Study Arms (4)

4mg buprenorphine

EXPERIMENTAL

4mg of buprenorphine will be given to a subset of participants immediately after naloxone administration.

Drug: Naloxone Nasal Spray

8mg buprenorphine

EXPERIMENTAL

8mg of buprenorphine will be given to a subset of participants immediately after naloxone administration.

Drug: Naloxone Nasal Spray

16mg buprenorphine

EXPERIMENTAL

16mg of buprenorphine will be given to a subset of participants immediately after naloxone administration.

Drug: Naloxone Nasal Spray

24mg buprenorphine

EXPERIMENTAL

24mg of buprenorphine will be given to a subset of participants immediately after naloxone administration.

Drug: Naloxone Nasal Spray

Interventions

Naloxone Nasal Spray DRUG

IN naloxone will be administered to participants, after which a single dose of buprenorphine will be given to participants

16mg buprenorphine; 24mg buprenorphine; 4mg buprenorphine; 8mg buprenorphine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years or older
• Speak fluent English
• Medically cleared to take study medication
• Willing to comply with the study protocol
• Provides urine sample that tests positive for fentanyl
• Current moderate to severe opioid use disorder

You may not qualify if:

• Significant cognitive impairment resulting in inability to provide informed consent (e.g., severe dementia or intellectual disability)
• Unable to read or understand study questions with assistance from the research staff
• Medical symptoms interfering with their ability to answer study questions
• Psychiatric symptoms interfering with their ability to answer survey questions
• Currently enrolled and taking medications for OUD
• Pregnant or Breastfeeding
• Taking medication contraindicated with study medication
• Deemed by the principal investigator or medical team to not be a good fit for the study protocol.
• Current or history of hypo/hypertension (i.e., no less than 90/60, no greater than 140/90) or adverse cardiovascular event in the past three years (e.g. significant cardiac arrhythmia, myocardiac infarction, endocarditis).

Sponsors & Collaborators

• Johns Hopkins University: lead
• Cure Addiction Now: collaborator

Study Sites (1)

Johns Hopkins School of Medicine

Baltimore, Maryland, 21224, United States

RECRUITING

Related Publications (9)

• Bergeria CL, Strain EC. Opioid Use Disorder: Pernicious and Persistent. Am J Psychiatry. 2022 Oct;179(10):708-714. doi: 10.1176/appi.ajp.20220699. No abstract available.

  PMID: 36181330 BACKGROUND

• Antoine D, Huhn AS, Strain EC, Turner G, Jardot J, Hammond AS, Dunn KE. Method for Successfully Inducting Individuals Who Use Illicit Fentanyl Onto Buprenorphine/Naloxone. Am J Addict. 2021 Jan;30(1):83-87. doi: 10.1111/ajad.13069. Epub 2020 Jun 23.

  PMID: 32572978 BACKGROUND

• Varshneya NB, Thakrar AP, Hobelmann JG, Dunn KE, Huhn AS. Evidence of Buprenorphine-precipitated Withdrawal in Persons Who Use Fentanyl. J Addict Med. 2022 Jul-Aug 01;16(4):e265-e268. doi: 10.1097/ADM.0000000000000922. Epub 2021 Nov 23.

  PMID: 34816821 BACKGROUND

• Randall A, Hull I, Martin SA. Enhancing Patient Choice: Using Self-administered Intranasal Naloxone for Novel Rapid Buprenorphine Initiation. J Addict Med. 2023 Mar-Apr 01;17(2):237-240. doi: 10.1097/ADM.0000000000001073. Epub 2022 Sep 22.

  PMID: 36149001 BACKGROUND

• Greenwald MK, Herring AA, Perrone J, Nelson LS, Azar P. A Neuropharmacological Model to Explain Buprenorphine Induction Challenges. Ann Emerg Med. 2022 Dec;80(6):509-524. doi: 10.1016/j.annemergmed.2022.05.032. Epub 2022 Aug 6.

  PMID: 35940992 BACKGROUND

• Center for Substance Abuse Treatment. Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction. Rockville (MD): Substance Abuse and Mental Health Services Administration (US); 2004. Report No.: (SMA) 04-3939. Available from http://www.ncbi.nlm.nih.gov/books/NBK64245/

  PMID: 22514846 BACKGROUND

• Greenwald MK. Heroin craving and drug use in opioid-maintained volunteers: effects of methadone dose variations. Exp Clin Psychopharmacol. 2002 Feb;10(1):39-46. doi: 10.1037//1064-1297.10.1.39.

  PMID: 11866251 BACKGROUND

• Wong JSH, Nikoo M, Westenberg JN, Suen JG, Wong JYC, Krausz RM, Schutz CG, Vogel M, Sidhu JA, Moe J, Arishenkoff S, Griesdale D, Mathew N, Azar P. Comparing rapid micro-induction and standard induction of buprenorphine/naloxone for treatment of opioid use disorder: protocol for an open-label, parallel-group, superiority, randomized controlled trial. Addict Sci Clin Pract. 2021 Feb 12;16(1):11. doi: 10.1186/s13722-021-00220-2.

  PMID: 33579359 BACKGROUND

• D'Onofrio G, Hawk KF, Perrone J, Walsh SL, Lofwall MR, Fiellin DA, Herring A. Incidence of Precipitated Withdrawal During a Multisite Emergency Department-Initiated Buprenorphine Clinical Trial in the Era of Fentanyl. JAMA Netw Open. 2023 Mar 1;6(3):e236108. doi: 10.1001/jamanetworkopen.2023.6108.

  PMID: 36995717 BACKGROUND

MeSH Terms

Conditions

Opioid-Related Disorders

Condition Hierarchy (Ancestors)

Narcotic-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Study Officials

• Cecilia Bergeria, PhD

  Johns Hopkins School of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Cecilia Bergeria, PhD

CONTACT

410-550-1979; cberge21@jhmi.edu

Anjalee Sharma, PhD

CONTACT

asharm58@jh.edu

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: single-ascending dose

Study Record Dates

• First Submitted: October 2, 2023
• First Posted: October 18, 2023
• Study Start: January 9, 2024
• Primary Completion: January 1, 2026
• Study Completion: January 1, 2026
• Last Updated: January 17, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)