Buprenorphine Induction for Fentanyl Dependent Opioid Users

July 5, 2023 updated by: Sarah Kawasaki, Milton S. Hershey Medical Center

Pilot Study to Look at Feasibility of Testing and Treatment of Combination Fentanyl and Opioid Dependent Individuals With Different Buprenorphine Induction Methods

The overall goal of this pilot study is to characterize illicit fentanyl and combination fentanyl and opioid dependence explicitly, by assessing physiologic barriers to effective buprenorphine induction. Results from this pilot study may make a case for a larger feasibility study to be conducted through the Clinical Trials Network at the National Institutes of Drug Abuse.

The primary hypothesis is that individuals dependent on illicit fentanyl and combination fentanyl and opioids will have difficulty with standard buprenorphine induction, and will need a modified approach. The primary outcome measure will be retention on buprenorphine at seven days post induction. The secondary outcome measures will be objective precipitated withdrawal and the rate of patients requiring or requesting to initiate methadone due to intolerance of buprenorphine.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Illicit synthetic fentanyl is found in increasing proportions of illicit drug samples, and negatively influences how buprenorphine is used on the street to help with subjective withdrawal symptoms. In the clinic, it has been observed among individuals positive for fentanyl that initiation of buprenorphine is difficult. When spontaneous withdrawal, normally the signal that the patient is ready to initiate buprenorphine, and buprenorphine is given, withdrawal symptoms often seem to increase. It is unclear whether this represents precipitated withdrawal versus progressing spontaneous withdrawal, but the standard clinical approach has been to wait for more withdrawal symptoms and time to elapse before trying another test dose. In this population, waiting is a clinically problematic strategy as many patients in continuing withdrawal would resume opioid use rather than try buprenorphine again. To date, there has been one study noting that fentanyl dependent patients are retained at equal rates to patients with heroin dependence, but this study was observational, retrospective and small. An alternative approach to induction would rapidly provide high doses of buprenorphine initially. The theory behind rapid induction would be either that the robust withdrawal observed is actually spontaneous withdrawal, calling for a higher initial buprenorphine dosing regimen, or that some of the withdrawal observed may be precipitated, but rapidly and fully occupying the receptors with partial agonist produces enough agonist effect to subdue precipitated withdrawal. If found to be superior to standard induction, the high dose induction regimen could be immediately implemented in primary care settings. Or, if buprenorphine cannot be initiated for a given patient, a full opioid agonist, namely methadone, may be the best first step, suggesting methadone as a first-line treatment for those dependent on fentanyl and other high potency synthetics. Methadone administration is currently restricted to specially licensed opioid treatment programs and not widely available across clinical settings where buprenorphine can be initiated. If the availability of methadone rescue in this study proves useful, it would support a larger case for regulatory reforms to make methadone more widely available beyond traditional OTPs.

The study proposed here would be the first pilot study to assess the extent that synthetic opioid dependence prevents successful induction with buprenorphine-naloxone. Programs like the Pennsylvania Psychiatric Institute's opioid treatment program have been set up to serve rural and impoverished small urban communities that have become the epicenter of the opioid epidemic. The need to deliver evidence-based treatment effectively is paramount, especially during a window of time in which an individual desiring treatment and having access to that treatment is vanishingly small. A difficult initiation with substantial withdrawal symptoms can derail motivation that can lead to treatment abandonment. A rapid assessment of whether individuals cannot complete buprenorphine-naloxone induction who have been using illicit fentanyl or combination fentanyl with other opioids is a starting point to change management of this growing set of individuals.

Study Type

Interventional

Enrollment (Estimated)

30

Phase

  • Early Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • Pennsylvania
      • Harrisburg, Pennsylvania, United States, 17110
        • Recruiting
        • The Pennsylvania Psychiatric Institute
        • Contact:
        • Principal Investigator:
          • Sarah Kawasaki, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 97 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  1. 18 years of age or older
  2. Diagnosis of opioid use disorder (OUD) as determined through routine clinical care
  3. Positive for fentanyl on point of care urine drug screen
  4. Ability to read, write, and comprehend English
  5. Patients willing to start buprenorphine at the onset of treatment (e.g., clinical intake)
  6. Patients who need to initiate a buprenorphine induction at home must have an operating smartphone or tablet device with video capability.

Exclusion Criteria:

  1. Initiating maintenance treatment that does not include MAT or switching to a maintenance treatment that does not include MAT (i.e.: detoxification and counseling treatment only without MAT, or planning to enter methadone treatment).
  2. Judged by the evaluating physician or allied clinician to need a higher level of care (i.e.: residential or inpatient treatment)
  3. Pregnant
  4. Patients desiring to start methadone or naltrexone at the onset of treatment (e.g., clinical intake)
  5. Patients who are unable to stay in the clinic for the induction period.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
No Intervention: Standard Dose
Standard dose induction Visit 1 Day 1 (intake/baseline) Participants will commence induction with a dose of 4mg if COWS is above 7. If COWS is below 7, participant will be instructed to return the next day, so that COWS can be above 7 to start the study.
Experimental: Macro or High Dose
Macro or High Dosing Visit 1 Day 1 (intake/baseline) Participants will commence induction with a dose of 4mg if COWS is above 7. If COWS is below 7, participant will be instructed to return the next day, so that COWS can be above 7 to start the study. (These participants can still be in the study and will only have to re-do a baseline COW's on the day they come back to the clinic, which will then be considered their day 1).
Drug: Buprenorphine/naloxone
Buprenorphine/Naloxone induction via a standard dose protocol
Experimental: Micro or Low Dose
Micro or Low Dose Visit 1 Day 1 (intake/baseline) Participants will commence induction with a dose of 4mg if COWS is above 7. If COWS is below 7, participant will be instructed to return the next day, so that COWS can be above 7 to start the study. (These participants can still be in the study and will only have to re-do a baseline COW's on the day they come back to the clinic, which will then be considered their day 1).
Drug: Buprenorphine/naloxone
Buprenorphine/Naloxone induction via a standard dose protocol

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of patients on Buprenorphine at the end of 7 day induction period
Time Frame: 7 days
Number of patients who are able and willing to receive a prescription for Buprenorphine at the end of a 7 day induction period. This will be measured by manual counts. The patient will be scored as 0 (for not able/willing to receive a prescription for bup) or 1 (for able/willing to receive a prescription for bup)
7 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Opioid withdrawal assessment
Time Frame: 7 days
Opioid withdrawal assessment as measured by COW's and SOW's. The COWS assessment is on a 0-48 point scale, with scores of 5 or higher indicating mild or greater withdrawal symptoms. SOWS is on a 0-30 point scale, with scores of greater than 1 indicating mild withdrawal symptoms.
7 days

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Attrition rate measures
Time Frame: 7 days
A measure of attrition rate. This will be assessed through manual counts either by the patient verbally stating their intention to withdraw from the study or wishing to initiate Methadone treatment.
7 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Milton S. Hershey Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 9, 2022

Primary Completion (Estimated)

February 22, 2024

Study Completion (Estimated)

June 22, 2024

Study Registration Dates

First Submitted

March 1, 2021

First Submitted That Met QC Criteria

March 8, 2021

First Posted (Actual)

March 12, 2021

Study Record Updates

Last Update Posted (Actual)

July 7, 2023

Last Update Submitted That Met QC Criteria

July 5, 2023

Last Verified

July 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • STUDY00016153

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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