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Opioid Use DisorderPhase 3NBIMNCT06089707

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

A Phase 3 study testing Naloxone Nasal Spray in people with Opioid Use Disorder, run by University of Maryland, Baltimore at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Opioid Use Disorder
What is being tested?
Naloxone Nasal Spray
Could I receive a placebo?
No, everyone receives an active treatment
How many people
3 participants
Where
1 siteUnited States
Study dates
9 Jan 2024to 1 Jan 2030
Phase
Phase 3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 18 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

Who cannot join

  • 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
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  • 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).

Trial locations and contacts

1 site in 1 country.

United States1 site
  • Johns Hopkins School of Medicine

    Baltimore, Maryland, 21224

Other trials in United States

About this study

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.

Read the detailed description

Emergent data suggest that individuals with fentanyl use experience prolonged, uncomfortable buprenorphine inductions that can commonly result in instances of unintended precipitated withdrawal. Buprenorphine induction in the fentanyl era can take multiple days, which is time intensive and increases the risk for treatment attrition. Novel methods that transition patients quickly and safely from fentanyl to buprenorphine are needed.

The proposed project will evaluate the feasibility and acceptability of naloxone-facilitated buprenorphine inductions among individuals with recent fentanyl exposure. The project consists of a single ascending dose study to assess feasibility and acceptability of naloxone-facilitated buprenorphine inductions.

Participants with opioid use disorder with fentanyl exposure who are not receiving medications for opioid use disorder will complete a brief phone or online prescreen to assess initial eligibility. Potentially eligible participants will be contacted by research staff to complete an in-person screen and informed consent form with a staff member and discuss the study before providing voluntary informed consent to participate. The screen contains structured demographics, substance use, and overall health questions from standard assessments and from internally developed survey items in order to determine study specific eligibility.

Eligible participants will enroll in a 2-3 day residential stay at a clinical research unit at Johns Hopkins University Bayview Campus. Throughout the residential stay, participants will complete frequent measures of withdrawal, craving, and anxiety. Participants may be maintained on hydromorphone for the first 24 hours depending on the timing of the participants admission. In a single-ascending dose design, the investigators will incrementally assess the tolerability of 4, 8, 16, and 24 mg of buprenorphine following naloxone administration (Narcan, 4 mg) among 3 participants per dose condition (e.g., 3 participants will receive 4 mg buprenorphine following naloxone administration then 3 new participants will receive 8 mg buprenorphine following naloxone administration, etc.). Immediately before naloxone administration and in 15-minute increments for 2 hours following naloxone administration, participants will be assessed for opioid withdrawal. These assessments will characterize the naloxone-induced opioid withdrawal and any evidence for buprenorphine-precipitated withdrawal. Following administration of buprenorphine, if there is no evidence of buprenorphine precipitated withdrawal within 45 minutes, the investigators will administer another dose of buprenorphine and will continue to dose the participant until the participant reaches stabilization (between 16mg and 24mg). The participant will stay an additional night for observation and will be discharged on the third day. All participants will be discharged with a short supply of buprenorphine and will be connected to a medical provider for continued buprenorphine prescribing. The Clinical Opiate Withdrawal scale (COWS) and the Subjective Opiate Withdrawal Scale (SOWS) will be assessed at regular intervals, multiple times throughout the stay to monitor withdrawal.

Being tested
Naloxone Nasal Spray
Keywords
buprenorphine, fentanyl, initiation to treatment
Medical subject headings
Opioid-Related Disorders

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Naloxone Nasal SprayDrug

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

Study groups in NCT06089707
Study groupRoleWhat they receive
4mg buprenorphineExperimental4mg of buprenorphine will be given to a subset of participants immediately after naloxone administration.
Receives: Drug: Naloxone Nasal Spray
8mg buprenorphineExperimental8mg of buprenorphine will be given to a subset of participants immediately after naloxone administration.
Receives: Drug: Naloxone Nasal Spray
16mg buprenorphineExperimental16mg of buprenorphine will be given to a subset of participants immediately after naloxone administration.
Receives: Drug: Naloxone Nasal Spray
24mg buprenorphineExperimental24mg of buprenorphine will be given to a subset of participants immediately after naloxone administration.
Receives: Drug: Naloxone Nasal Spray

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: After administration of first dose of buprenorphine up to 8 hours

  2. 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.

    Measured: 3 days

  3. 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

    Measured: After initial buprenorphine dose up to 24 hours

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Oct 2023
  2. Study start9 Jan 2024
  3. Primary completion1 Jan 2030 (estimated)
  4. Study completion1 Jan 2030 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Model description
single-ascending dose
Masking
None (open label)
Enrolment
3 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06089707
Sponsor's protocol ID
IRB00392041
Acronym
NBIM
Status last verified
Jul 2026
First submitted
2 Oct 2023
Last updated
27 Jul 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 36181330
  • 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.

    PubMed 32572978
  • 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.

    PubMed 34816821
  • 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.

    PubMed 36149001
  • 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.

    PubMed 35940992
  • 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/

    PubMed 22514846
  • 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.

    PubMed 11866251
  • 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.

    PubMed 33579359
  • 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.

    PubMed 36995717

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Naloxone Nasal Spray in people with Opioid Use Disorder, run by University of Maryland, Baltimore at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 27 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Peak opioid withdrawal as assessed by the Subjective Opiate Withdrawal Scale (SOWS) (time frame: After administration of first dose of buprenorphine up to 8 hours). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06089707, which also lists 9 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jul 2026.

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