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Buprenorphine Induction for Fentanyl Dependent Opioid Users

Primary Purpose

Opioid Dependence Fentanyl

Status
Recruiting
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
Buprenorphine/naloxone
Sponsored by
Milton S. Hershey Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Opioid Dependence Fentanyl

Eligibility Criteria

18 Years - 99 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

  • The Pennsylvania Psychiatric InstituteRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

No Intervention

Experimental

Experimental

Arm Label

Standard Dose

Macro or High Dose

Micro or Low Dose

Arm Description

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.

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).

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).

Outcomes

Primary Outcome Measures

Number of patients on Buprenorphine at the end of 7 day induction period
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)

Secondary Outcome Measures

Opioid withdrawal assessment
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.

Full Information

First Posted
March 1, 2021
Last Updated
July 5, 2023
Sponsor
Milton S. Hershey Medical Center
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1. Study Identification

Unique Protocol Identification Number
NCT04794790
Brief Title
Buprenorphine Induction for Fentanyl Dependent Opioid Users
Official Title
Pilot Study to Look at Feasibility of Testing and Treatment of Combination Fentanyl and Opioid Dependent Individuals With Different Buprenorphine Induction Methods
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 9, 2022 (Actual)
Primary Completion Date
February 22, 2024 (Anticipated)
Study Completion Date
June 22, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Milton S. Hershey Medical Center

4. Oversight

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
Data Monitoring Committee
No

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Opioid Dependence Fentanyl

7. Study Design

Primary Purpose
Treatment
Study Phase
Early Phase 1
Interventional Study Model
Parallel Assignment
Model Description
We are attempting to characterize the particular problem of prolonged precipitated withdrawal in individuals with fentanyl dependence through a quasi-experimental study, which will enroll 20 to 30 individuals at the PPI OTP, who are using fentanyl and/or combination of fentanyl and opioids but desiring buprenorphine naloxone induction. There will be a standard treatment arm, then a micro dose and macro dose arm.
Masking
None (Open Label)
Allocation
Randomized
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Standard Dose
Arm Type
No Intervention
Arm Description
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.
Arm Title
Macro or High Dose
Arm Type
Experimental
Arm Description
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).
Arm Title
Micro or Low Dose
Arm Type
Experimental
Arm Description
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).
Intervention Type
Drug
Intervention Name(s)
Buprenorphine/naloxone
Intervention Description
Buprenorphine/Naloxone induction via a standard dose protocol
Primary Outcome Measure Information:
Title
Number of patients on Buprenorphine at the end of 7 day induction period
Description
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)
Time Frame
7 days
Secondary Outcome Measure Information:
Title
Opioid withdrawal assessment
Description
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.
Time Frame
7 days
Other Pre-specified Outcome Measures:
Title
Attrition rate measures
Description
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.
Time Frame
7 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
99 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: 18 years of age or older Diagnosis of opioid use disorder (OUD) as determined through routine clinical care Positive for fentanyl on point of care urine drug screen Ability to read, write, and comprehend English Patients willing to start buprenorphine at the onset of treatment (e.g., clinical intake) Patients who need to initiate a buprenorphine induction at home must have an operating smartphone or tablet device with video capability. Exclusion Criteria: 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). Judged by the evaluating physician or allied clinician to need a higher level of care (i.e.: residential or inpatient treatment) Pregnant Patients desiring to start methadone or naltrexone at the onset of treatment (e.g., clinical intake) Patients who are unable to stay in the clinic for the induction period.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Sarah Kawasaki, MD
Phone
717-782-2781
Email
skawasaki@pennstatehealth.psu.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Rachel C Zimmerman, MS
Phone
717-782-2118
Email
rzimmerman10@pennstatehealth.psu.edu
Facility Information:
Facility Name
The Pennsylvania Psychiatric Institute
City
Harrisburg
State/Province
Pennsylvania
ZIP/Postal Code
17110
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Rachel Zimmerman, MS
Phone
717-782-6844
Email
rzimmerman10@pennstatehealth.psu.edu
First Name & Middle Initial & Last Name & Degree
Sarah Kawasaki, MD

12. IPD Sharing Statement

Plan to Share IPD
Undecided
Citations:
PubMed Identifier
30873700
Citation
Mars SG, Rosenblum D, Ciccarone D. Fentanyl: the many challenges ahead. Addiction. 2019 May;114(5):785-786. doi: 10.1111/add.14587. Epub 2019 Mar 15. No abstract available.
Results Reference
background
PubMed Identifier
31563098
Citation
Silverstein SM, Daniulaityte R, Martins SS, Miller SC, Carlson RG. "Everything is not right anymore": Buprenorphine experiences in an era of illicit fentanyl. Int J Drug Policy. 2019 Dec;74:76-83. doi: 10.1016/j.drugpo.2019.09.003. Epub 2019 Sep 25.
Results Reference
background
PubMed Identifier
23961726
Citation
Hser YI, Saxon AJ, Huang D, Hasson A, Thomas C, Hillhouse M, Jacobs P, Teruya C, McLaughlin P, Wiest K, Cohen A, Ling W. Treatment retention among patients randomized to buprenorphine/naloxone compared to methadone in a multi-site trial. Addiction. 2014 Jan;109(1):79-87. doi: 10.1111/add.12333. Epub 2013 Oct 9.
Results Reference
background

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Buprenorphine Induction for Fentanyl Dependent Opioid Users

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