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Trial registered on ANZCTR


Registration number
ACTRN12621001011875
Ethics application status
Approved
Date submitted
4/06/2021
Date registered
2/08/2021
Date last updated
2/08/2021
Date data sharing statement initially provided
2/08/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
WHOS Coming Off Buprenorphine: understanding the experience of withdrawing from buprenorphine medication in the treatment of opioid dependence
Scientific title
Characterizing withdrawal from depot buprenorphine: an observational case series of opioid dependent clients withdrawal from buprenorphine formulations in a residential treatment setting
Secondary ID [1] 304400 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Opioid Dependence (Opioid Use Disorder) 322193 0
Opioid Withdrawal Syndrome 322194 0
Condition category
Condition code
Mental Health 319883 319883 0 0
Addiction

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
Participants will be admitted into a 16-week residential rehabilitation program, during which they will undertake withdrawal from their routinely prescribed buprenorphine medication.

There are two groups of participants - those withdrawing from depot buprenorphine, and those withdrawing from sublingual buprenorphine (determined by the medication prescribed in the community prior to admission - i.e., self-selected comparison groups). It is an open-label study with participants and treatment providers aware of the medication being used.

Arm 1: Participants in the depot buprenorphine group will recieve one dose of 64mg modified release Subcutaneous depot buprenorphine injection (Buvidal Monthly) administered in the first week of treatment in the rehabilitation program. No further doses of buprenorphine will be administered to the participants in the depot buprenorphine arm.

Arm 2: Doses for participants in the sublingual buprenorphine group will be individualsed according to the participant's usual dose at entry into the program (commencing from a maximum of 24mg daily dose) and undertake a gradual dose taper with weekly dose reductions of 2-4mg per week to 0mg over the first 8 weeks of the program - with flexibility of up to a 2 week extension (ie reaching zero mg by week 10), determined by each participant in consultation with the study medical officer. Sublingual buprenorphine is supervised by nursing staff, and administered once a day (mornings).

All medications are supervised in the residential unit, and adherence to medications will be documented by review of medication charts.

All participants (both arms) will undergo routine psychosocial and group programs and activities of the residential service during the 16 week admission. These occupy approximately 6 hours a day and consist of health oriented psychoeducation, life skills training, exercise program, vocational activities (e.g. computer skills, literacy skills), relapse prevention counselling interventions, together with 'house meetings' and recreational activities. These services are delivered by mental health trained nurses, allied health and peer workers.
Intervention code [1] 321016 0
Not applicable
Comparator / control treatment
Outcomes for participants in the two arms (sublingual versus depot buprenorphine) will be compared. Both arms involve routine clinical care, with the study aiming to characterise the profile of the opiate withdrawal syndrome as participants in each arm discontinue their buprenorphine medication.
Control group
Active

Outcomes
Primary outcome [1] 327765 0
The primary outcome is the Clinical Opiate Withdrawal Scale (COWS) (Wesson and Ling 2003), an 11-item instrument that includes both subjective symptoms and objective signs of opiate withdrawal, and administered by trained nursing staff .
Timepoint [1] 327765 0
Data collected at baseline (entry) and at weekly intervals over course of 16-week admission
Primary outcome [2] 328094 0
Subjective Opiate Withdrawal Scale (Handelsman et al 1987) measures the severity of subjective symptoms of opiate withdrawal using a 16-item checklist, and self-completed by participants.
Timepoint [2] 328094 0
Measured at baseline and at weekly intervals over the 16-week admission.
Primary outcome [3] 328095 0
Objective Opiate Withdrawal Scale (OOWS) (Handelsman et al 1987), is a 13-item scale that assesses signs of opiate withdrawal, and completed by training nursing staff.
Timepoint [3] 328095 0
Administered at baseline and at weekly intervals over the 16 week admission.
Secondary outcome [1] 396508 0
Adverse events: assessed by study medical officer assessment of participants
Timepoint [1] 396508 0
Assessed at structured medical reviews, at a minimum of 4-weekly intervals, and on completion of the study for each participant (week 16 or end of treatment). There is the capacity for more frequent assessment and management of adverse events as clinically indicated.
Secondary outcome [2] 396509 0
Completion of residential withdrawal episode, Operationalized as the participant remaining in the residential unit for at least 12 weeks following admission, and for at least 4 weeks after cessation of opioid medication. Audited from residential unit medical records.
Timepoint [2] 396509 0
Recorded at completion of protocol (16 week) or end-of-treatment for each participant.
Secondary outcome [3] 396527 0
Subjective measures of sleep using the Insomnia Severity Index (ISI) - a self-rated questionnaire.
Timepoint [3] 396527 0
ISI administered at baseline and weekly intervals over 16-week period
Secondary outcome [4] 396528 0
Objective measures of sleep using Actigraphy, Measures calculated will include sleep onset latency, total sleep duration, sleep efficiency, time spent in bed.
Timepoint [4] 396528 0
Actigraphy is a continous measurement over the 16-week protocol
Secondary outcome [5] 396529 0
Participant ratings of general health status: PROMIS29
Timepoint [5] 396529 0
PROMIS29 collected at baseline and 4 weekly intervals over the 16-week protocol
Secondary outcome [6] 396530 0
Urine drug screen assayed for buprenorphine (quantitative assays) .
Timepoint [6] 396530 0
At baseline and 4 week intervals over the 16-week protocol
Secondary outcome [7] 396531 0
Patient rated satisfaction and experience: measure using the Treatment Satisfaction Medication Questionnaire (TSQM), a validated compsote scale with 4 subscales.
Timepoint [7] 396531 0
TSQM collected at baseline and 4 weekly intervals over the 16-week protocol
Secondary outcome [8] 397620 0
Cravings for substance use, measured using a Visual Analogue Scale (0-100)
Timepoint [8] 397620 0
Measured at baseline and at weekly intervals over the 16-week protocol

Eligibility
Key inclusion criteria
In buprenorphine treatment for indication of opioid dependence, and willing to discontinue buprenorphine treatment in a long-term residential rehabilitation setting.
For participants in depot buprenorphine arm:
1. In buprenorphine treatment for at least 8 weeks prior to projected admission date
2. In treatment with Buvidal Monthly (64, 96 or 128mg) for at least 1 dose (administered 4±1 weeks), or Buvidal Weekly (16mg, 24mg or 32mg) for at least 4 doses (administered 7±2 days) prior to projected admission date.

For participants in SL buprenorphine arm:
1. In SL buprenorphine treatment for at least 8 weeks prior to projected admission date.
2. On a SL BPN dose of no greater than 24 mg daily in the week prior to admission
Minimum age
18 Years
Maximum age
80 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Likely to experience a withdrawal syndrome from another substance, including alcohol, BZDs, cannabis, opioids and stimulants. Operationalized as using substances on 4 days or more (on average) in the 4 weeks preceding the admission (ATOP Substance Use section - alcohol at 80gm per day; cannabis; benzodiazepines; amphetamine type substances, heroin or prescription opioids),
2. Active severe medical (e.g. unstable mental health, chronic pain) or social conditions (e.g. impending court case with likely custodial sentence) that mitigate against an admission for withdrawal from opioid agonist treatment .
3. Significant changes in use of other psychoactive medications in the 28 days prior to admission (e.g. antidepressant, anti-convulsant, antipsychotic medications). Exclusions include clients seeking to initiate, cease or substantially change their dose in the 28 days prior to admission, or during the admission.

Study design
Purpose
Natural history
Duration
Longitudinal
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
Mixed effects models for repeated measures (MMRM) regressions will be used to estimate overall rate of change and group differences in rate of change in primary and secondary outcomes. Within these models the simple effects of treatment type (depot vs sublingual) at weeks 0, 4, 8, 12 and 16 will be estimated using least-squares means. Logistic regression will be used to estimate the effect of treatment type on odds of successful completion of treatment.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW

Funding & Sponsors
Funding source category [1] 308769 0
Commercial sector/Industry
Name [1] 308769 0
Camurus Pty Ltd
Address [1] 308769 0
Hyde Park Hub
223 Liverpool St
Darlinghurst
NSW 2010
Country [1] 308769 0
Australia
Funding source category [2] 308777 0
Hospital
Name [2] 308777 0
SESLHD, Drug and Alcohol Services
Address [2] 308777 0
c/o The Langton Centre
591 South Dowling Street, Surry Hills, NSW, 2010
Country [2] 308777 0
Australia
Primary sponsor type
Government body
Name
South East Sydney Local Health District
Address
c/o TheLangton Centre, 591 South Dowling Street, Surry Hills, NSW 2010
Country
Australia
Secondary sponsor category [1] 309686 0
None
Name [1] 309686 0
Address [1] 309686 0
Country [1] 309686 0
Other collaborator category [1] 281844 0
University
Name [1] 281844 0
University of Sydney
Address [1] 281844 0
City Road, Camperdown NSW 2006
Country [1] 281844 0
Australia
Other collaborator category [2] 281845 0
Other Collaborative groups
Name [2] 281845 0
NSW Drug and Alcohol Clinical Research and Improvement Network
Address [2] 281845 0
c/o The Langton Centre,
591 South Dowling Street, Surry Hills, NSW 2010
Country [2] 281845 0
Australia
Other collaborator category [3] 281846 0
Charities/Societies/Foundations
Name [3] 281846 0
We Help OurSelves (WHOS)
Address [3] 281846 0
1Broughton Hall Building 195,
Glover Street
Lilyfield NSW 2040
Country [3] 281846 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 308684 0
South East Sydney Local Health District
Ethics committee address [1] 308684 0
c/o Prince of Wales Hospital, 320-346 Barker St, Randwick, NSW 2031
Ethics committee country [1] 308684 0
Australia
Date submitted for ethics approval [1] 308684 0
01/12/2020
Approval date [1] 308684 0
01/03/2021
Ethics approval number [1] 308684 0
2020/ETH01924

Summary
Brief summary
The introduction of long acting depot (modified release) buprenorphine subcutaneous injections in recent years is a significant addition to the medication options for the treatment of opioid dependence. These medications are long acting and enable 'once a month' doses rather than daily medication such as sublingual buprenorphine - which are often associated with inconvenience and cost for patients and health services.
However little is known about the nature of the withdrawal syndrome that occurs if patients discontinue depot buprenorphine medication. The aim of this study is to describe the profile of withdrawal signs and symptoms in participants discontinuing opioid treatment with a 4-weekly depot buprenorphine formulation, and to compare against the withdrawal profile of a parallel group of participants discontinuing opioid treatment using sublingual buprenorphine. Participants will be monitored over a 16-week admission in a residential rehabilitation unit that assists clients withdrawing from opioid agonist treatment; and participants will withdraw using the buprenorphine formulation they are prescribed prior to the admission (a non-randomised comparison group). The main outcome is opiate withdrawal severity (subjective and objective features) over the course of the admission, with secondary outcomes of cravings, adverse events, general heath, sleep measures and patient experience. .
Trial website
N/A
Trial related presentations / publications
N/A
Public notes
The study aims to address one of the key gaps in our understanding of the new long-acting depot buprenorphine: what is the nature of the withdrawal syndrome when stopping this treatment - compared to the withdrawal profile seen with more conventional sublingual buprenorphine reductions.

Contacts
Principal investigator
Name 111546 0
Prof Nicholas Lintzeris
Address 111546 0
South East Sydney Local Health District Drug and Alcohol Services
c/o The Langon Centre, 591 South Dowling Street, Surry Hills, NSW 2010
Country 111546 0
Australia
Phone 111546 0
+61419261675
Fax 111546 0
Email 111546 0
nicholas.lintzeris@health.nsw.gov.au
Contact person for public queries
Name 111547 0
Prof Nicholas Lintzeris
Address 111547 0
South East Sydney Local Health District Drug and Alcohol Services
c/o The Langon Centre, 591 South Dowling Street, Surry Hills, NSW 2010
Country 111547 0
Australia
Phone 111547 0
+61419261675
Fax 111547 0
Email 111547 0
nicholas.lintzeris@health.nsw.gov.au
Contact person for scientific queries
Name 111548 0
Prof Nicholas Lintzeris
Address 111548 0
South East Sydney Local Health District Drug and Alcohol Services
c/o The Langon Centre, 591 South Dowling Street, Surry Hills, NSW 2010
Country 111548 0
Australia
Phone 111548 0
+61419261675
Fax 111548 0
Email 111548 0
nicholas.lintzeris@health.nsw.gov.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Deidentified data regarding participants characteritics, treatment interventions and outcomes can be shared
When will data be available (start and end dates)?
After completion of project (Jan 2023). Data requests will be available for up to 7 years after the completion of the study.
Available to whom?
To researchers upon written request to the PI (Prof Nicholas Lintzeris)
Available for what types of analyses?
For secondary analyses and data pooling (e.g. metanalysis)
How or where can data be obtained?
Written request to prof Nicholas Lintzeris via email address
nicholas.lintzeris@health.nsw.gov.au
What supporting documents are/will be available?
Study protocol
Clinical study report
How or where can supporting documents be obtained?
Type [1] 11909 0
Study protocol
Citation [1] 11909 0
N/A
Link [1] 11909 0
Email [1] 11909 0
nicholas.lintzeris@health.nsw.gov.au
Other [1] 11909 0
Attachment [1] 11909 0
Type [2] 11910 0
Clinical study report
Citation [2] 11910 0
N/A
Link [2] 11910 0
Email [2] 11910 0
nicholas.lintzeris@health.nsw.gov.au
Other [2] 11910 0
Attachment [2] 11910 0
Summary results
No Results