Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12614001038684
Ethics application status
Approved
Date submitted
16/09/2014
Date registered
25/09/2014
Date last updated
26/11/2019
Date data sharing statement initially provided
29/10/2018
Date results provided
26/11/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
A pilot study examining the analgesic effect of ascending buprenorphine doses in opioid dependent people
Scientific title
A pilot study examining the analgesic effect of ascending buprenorphine doses in opioid dependent people
Secondary ID [1] 285349 0
none
Universal Trial Number (UTN)
U1111-1161-8062
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Pain 293072 0
Opioid dependence 293073 0
Condition category
Condition code
Anaesthesiology 293348 293348 0 0
Pain management
Mental Health 293373 293373 0 0
Addiction

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Examining the effect of administering a participants usual daily dose of sublingual buprenorphine (range 4-16mg)(in the form of buprenorphine-naloxone) compared with 150% and 200% of the usual daily dose, in buprenorphine maintained participants on experimental pain threshold and tolerance using the cold pressor test. Each dose condition will be tested once (single-dose only). Participants will have three wash out days in between each study session. To maintain the blind participants will receive the balance of their double dose, i.e. 100%. 50% or 0% of their usual dose at the end of the session so that participants receive a full 'double dose' (i.e. twice their usual maintenance dose) on the study day. Consistent with usual double dosing procedures, they will not receive a dose of buprenorphine on the day following the session. On the next two days of the washout period the participants usual dose will be administered. Study medication will be administered under supervised conditions and urine drug screening will be used to confirm substance use prior to each session.
Intervention code [1] 290266 0
Treatment: Drugs
Comparator / control treatment
Participants usual maintenance buprenorphine dose will be the control condition, and the comparator will be 150 and 200% of their buprenorphine dose. Depending on the dose administered at the start of the test day (100%, 150% or 200%) participants will the balance of their usual 'double dose' (100%, 50% or 0% of their dose) at the end of the test session so that participants receive their usual maintenance dose over the two day period. Administering double a buprenorphine dose to cover two days is part of standard treatment guidelines. On the next two days of the washout session the participants usual dose will be administered.The study is a within patient design so each participant will act as their own control and receive all three conditions. To maintain the blind placebo films will be administered so that total number of films in each session will be the same. Further, to maintain the blind participants will receive a blinded dose of buprenorphine+naloxone film dose at the end of the session which will contain the balance of their dose so that participants receive their usual maintenance dose in the form of a 'double dose' over the two day period.
Control group
Dose comparison

Outcomes
Primary outcome [1] 293181 0
Pain threshold (time with arm in the cold pressor bath until participant reports pain detection)
Timepoint [1] 293181 0
2 hours following buprenorphine dose
Primary outcome [2] 293201 0
Pain tolerance (total time with arm in the cold pressor bath until participant removes their arm)
Timepoint [2] 293201 0
2 hours after buprenorphine dose
Secondary outcome [1] 310536 0
Respiration (breaths per minute) observation visually
Timepoint [1] 310536 0
Baseline, 1h 50min, 2h 10min
Secondary outcome [2] 310537 0
Subjective effects of medication on 0 - 100mm Visual Analog Scale. Items measured on the scale include strength of drug effect, liking of drug effect, sedation, bad effects and intoxication. These measures are commonly assessed in drug administration studies.
Timepoint [2] 310537 0
One hour 50 minutes after buprenorphine administration
Secondary outcome [3] 310566 0
Blood pressure measures using a blood pressure machine
Timepoint [3] 310566 0
Baseline, 1h 50min, 2h 10min
Secondary outcome [4] 310567 0
Oxygen saturation measured with a pulse oximeter
Timepoint [4] 310567 0
Baseline, 1h 50min, 2h 10min
Secondary outcome [5] 310568 0
Cognitive effects measured with pen and paper test (DSST, Cancellation of 4s)
Timepoint [5] 310568 0
Baseline and one hour and 50 minutes
Secondary outcome [6] 310569 0
Self reported pain measured with visual analog scale
Timepoint [6] 310569 0
2h
Secondary outcome [7] 310573 0
Placebo/blind assessment (participant reports on a pen and paper form which condition they think they received on a study day)
Timepoint [7] 310573 0
2h 20 minutes

Eligibility
Key inclusion criteria
1. Being at least 18 - 60 years of age
2. Being of general good medical and psychiatric health
3. Female participants must not be pregnant or nursing, and must have agreed to use an acceptable method of birth control.
4. Be stable buprenorphine treatment, including being on a stable dose of buprenorphine (4-16mg/day) at least 10 days.
5. Be willing to and capable of signing an informed consent.
6. Primary language spoken is English
Minimum age
18 Years
Maximum age
60 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Potential participants must not:
1. Be dependent on alcohol, benzodiazepines, cannabis or other drugs of abuse that require immediate medical attention or be unsafe in the context of the study.
2. Be actively involved in another clinical trial.
3. Have a physiological, neurological or psychiatric illness (e.g. schizophrenia, Raynaud’s disease, urticaria, stroke) that would affect pain responses.
4. Be currently taking analgesic medication for a painful condition on a regular basis.
5. Be currently taking a medication known to affect pain response (e.g. antidepressants)
6. Be taking medications, herbal or vitamin supplements or other dietary supplements (eg grapefruit juice) that may interfere with the metabolism of the study medication.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Eligible participants that provide informed consent will be enrolled and randomized. The study pharmacist will dispense medications for each of the three study sessions according the randomization schedule. Study medication and placebos will be matched for appearance and dispensed in identical packaging so that the researchers and participants will not know what dose is administered on each session.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
A randomization schedule for the nine participants will be developed in advance using computer generated schedule. The study pharmacist will then dispense medication according to the randomization schedule in the order that participants are enrolled (from participant one to participant nine).
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
Intervention assignment
Crossover
Other design features
Within-patient design
Phase
Phase 4
Type of endpoint/s
Statistical methods / analysis
The primary outcome measures will be change in pain tolerance and threshold. Differences in pain tolerance and threshold will be examined using two-way repeated measures ANOVA, or mixed models if there is missing data.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
16/10/2014
Actual
22/10/2014
Date of last participant enrolment
Anticipated
30/03/2018
Actual
9/04/2018
Date of last data collection
Anticipated
Actual
29/05/2018
Sample size
Target
9
Accrual to date
Final
8
Recruitment in Australia
Recruitment state(s)
NSW

Funding & Sponsors
Funding source category [1] 289963 0
Government body
Name [1] 289963 0
Drug and Alcohol Services, South Eastern Sydney Local Health District, Departmental funds.
Country [1] 289963 0
Australia
Funding source category [2] 289980 0
Government body
Name [2] 289980 0
NHMRC Research Fellowship
Country [2] 289980 0
Australia
Primary sponsor type
Government body
Name
South Eastern Sydney Local Health District
Address
The Langton Centre, 591 South Dowling St, Surry Hills, NSW, 2010
Country
Australia
Secondary sponsor category [1] 288654 0
None
Name [1] 288654 0
Address [1] 288654 0
Country [1] 288654 0
Other collaborator category [1] 278156 0
University
Name [1] 278156 0
University of New South Wales, National Drug and Alcohol Centre
Address [1] 278156 0
22-32 King St, Randwick, NSW, 2052
Country [1] 278156 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 291676 0
Human Research Ethics Committee South Eastern Sydney Local Health District
Ethics committee address [1] 291676 0
Ethics committee country [1] 291676 0
Australia
Date submitted for ethics approval [1] 291676 0
Approval date [1] 291676 0
15/07/2014
Ethics approval number [1] 291676 0
141088 (HREC/14/POWH/208)

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 51478 0
Dr Suzanne Nielsen
Address 51478 0
University of New South Wales
National Drug and Alcohol Research Centre
22-32 King St
Randwick 2031 NSW
Country 51478 0
Australia
Phone 51478 0
+ 61 2 8936 1017
Fax 51478 0
Email 51478 0
[email protected]
Contact person for public queries
Name 51479 0
Suzanne Nielsen
Address 51479 0
University of New South Wales
National Drug and Alcohol Research Centre
22-32 King St
Randwick 2031 NSW
Country 51479 0
Australia
Phone 51479 0
+ 61 2 8936 1017
Fax 51479 0
Email 51479 0
[email protected]
Contact person for scientific queries
Name 51480 0
Suzanne Nielsen
Address 51480 0
University of New South Wales
National Drug and Alcohol Research Centre
22-32 King St
Randwick 2031 NSW
Country 51480 0
Australia
Phone 51480 0
+ 61 2 8936 1017
Fax 51480 0
Email 51480 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Consent was not gained for data sharing from participants.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseEffects of ascending buprenorphine doses on measures of experimental pain: A pilot study.2019https://dx.doi.org/10.1016/j.jsat.2019.07.002
N.B. These documents automatically identified may not have been verified by the study sponsor.