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Trial registered on ANZCTR


Registration number
ACTRN12612000288820
Ethics application status
Approved
Date submitted
7/03/2012
Date registered
12/03/2012
Date last updated
26/11/2019
Date data sharing statement initially provided
26/11/2019
Date results provided
26/11/2019
Type of registration
Retrospectively registered

Titles & IDs
Public title
Optimising Management of acute pain in Opioid Substitution Therapy patients: A pilot laboratory randomised study
Scientific title
Optimising management of acute pain in opioid substitution therapy patients: A pilot laboratory randomised study.
Secondary ID [1] 280083 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute pain in opioid dependence 285994 0
Condition category
Condition code
Mental Health 286180 286180 0 0
Addiction
Anaesthesiology 286214 286214 0 0
Pain management

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
There are three participant groups.
i) Participants on methadone
ii) Participants on buprenorphine (or buprenorphine+naloxone)
iii) A healthy control group.
The procedures for the first two participant groups (those on methadone and those on a buprenorphine product) will attend four sessions each, in random order, with five days washout between each session. Each session is approximately three hours long. The cold pressor test is administered two hours after baseline.
The four sessions (which are in random order) are:
(1) STANDARD OPIOID MAINTENANCE MEDICATION DOSE ONLY
Standard methadone oral liquid (the participants own regular dose) OR buprenorphine (+/- naloxone) (the participants own regular dose of buprenorphine sublingual tablet or buprenorphine plus naloxone (4:1 ratio) depending on what the participants usual OST medication is. NB naloxone is only given as part of the Suboxone combination product if that is the participants usual opioid medication, naloxone is not absorbed by the sublingual route. Naloxone is not given to other participants unless it is a part of their routine opioid agonist maintenance medication.
(2) THIRTY PERCENT INCREASE OF STANDARD OPIOD MAINTENANCE DOSE
In this session a 30% increase in the participants own standard methadone liquid dose or buprenorphine (+/- naloxone) sublingual tablet or film dose is given. The actual dose will depend on participants base dose.
(3) OXYCODONE DOSE
In this session the participants standard methadone oral liquid dose or buprenorphine (+/- naloxone) sublingual dose plus oral immediate release oxycodone tablets, dose to be equivalent to 30% of usual maintenance methadone / buprenorphine (+/- naloxone) (Note - the actual dose will depend on the participants regular dose of methadone or buprenorphine which will be used to calculate the oxycodone dose).
(4) GABAPENTIN DOSE
the participants standard methadone oral liquid dose / or buprenorphine (+/- naloxone) sublingual dose plus 600mg gabapentin oral tablet.

The healthy control (non-methadone, non-buprenorphine) subjects will attend the study laboratory for three 3-hour study sessions, each separated by at least 5 days. At each session, the cold pressor test will be conducted 2 hours after baseline. In random order each participant will receive

(1) placebo (either matched placebo for gabapentin or matched placebo for oxycodone or both, depending on active condition)

(2) immediate release oxycodone 5mg oral tablet

(3) 600mg gabapentin oral tablet



Cold Pressor Procedures:
Acute pain response will be measured the two hour time point using a standardized cold pressor trial. With this widely used experimental pain induction method, a body limb (typically the arm) is immersed cold water, reliably producing an aching pain of clinical quality and intensity.

Cold Pressor testing approach:

The participants will be seated in a comfortable chair, and asked to roll up their sleeve and remove watches or jewelry from their non-dominant arm and hand. Participants will then place their forearm (to above the elbow) into the cold water bath with fingers wide apart. No contact will be made with the side or bottom of the container. As soon as the limb is fully immersed, timing will begin. A water pump is placed in the cold-water container to prevent laminar warming around the immersed limb. Participants will not be spoken to during the cold-water immersion in order to minimize any distraction or cues for time that could adversely influence pain detection and tolerance levels.

Participants will be told to inform the research staff when (a) pain is initially detected (threshold). Then they will be asked to keep the immersed limb in the container until pain can no longer be tolerated and then remove their arm (b) the time when they remove their arm from the bath is recorded by the research staff (tolerance).
Intervention code [1] 284406 0
Treatment: Drugs
Comparator / control treatment
An increase in the participants usual methadone or buprenorphine (+/- naloxone) dose (30%) is compared with the equivalent dose of oxycodone, and also comapred with placebo. Placebos are available for oxycodone, gabapentin, methadone and buprenorphine (+/- naloxone) are identical on appearance to the active medications being used.
Control group
Placebo

Outcomes
Primary outcome [1] 286649 0
Change in pain threshold and tolerance using a cold pressor model of pain
Timepoint [1] 286649 0
Cold pressor intervention occurs at 2h post baseline. Methadone or buprenorphine (+/- naloxone) administration occurs at baseline. Gabapentin is administered at t = 60 min. Oxycodone is administered at t = 90 min.
Secondary outcome [1] 296374 0
Physiological measures (blood pressure, pulse, respiratory rate, pulse oxymetry, pupil diameter).
Timepoint [1] 296374 0
Physiological measurements are recorded at baseline, t = 1h50min, t = 2h 10min and t = 3h.
Secondary outcome [2] 296465 0
Subjective measures of drug effections (measured with a visual analog scale of sedation, good and bad drug effects, drug liking and intoxication)
Timepoint [2] 296465 0
Measured at t= 1h 50 min and 2h 10 min (before and after the cold pressor test)
Secondary outcome [3] 296466 0
A congitive test (the Digit Symbol Substution Task)
Timepoint [3] 296466 0
At Baseline and t - 1h 50 min
Secondary outcome [4] 296467 0
Adverse events
Timepoint [4] 296467 0
Adverse events will be documented as they occur. Subjects will be asked about adverse events at the completion of each session. Adverse events will be reviewed by a study medical officer at the end of each session.

Adverse events may be detected by routine monitoring of physiological measures. Potential side effects of study medication or from the cold pressor procedure will be elicited by standard questioning at the end of each session. Adverse events may also be obverved by study staff during the session.

Eligibility
Key inclusion criteria
(1) patients with stable OST dose for >4weeks (methadone and buprenorphine groups)
or opiate naive ie have never been dependent on opiates and have not used any opiates in the last 4 weeks (control group);
(2) participants opioid substitution dose between 40-100mg of methadone or 8-24mg buprenorphine;
(3) aged 18 – 65 yrs; and
(4) participants give informed consent
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
(1) severe acute medical or psychiatric conditions
(2) pregnancy
(3) are currently using or dependent to other substances such as alcohol, benzodiazepines, cocaine, psychostimulants or heroin;
(4) moderate or severe pain within 4 weeks prior to the study
(5) are currently participating in another research project that may interfere with the present study;
(6) on medications with significant pharmacokinetic/dynamic interaction with study medications
(7) cold urticaria

Eligible participants will be deemed healthy by the study physician. Participants with a current pain condition will be excluded from the study as concurrent pain conditions may confound the results from the cold pressor test, which is being used as a model for acure pain. One arm of the study involves healthy volunteers, and the other two arms of the study are a group pf patients on methadone and a group of patients on buprenorphine.

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)
The study is a randomised, controlled, double-blinded, double-dummy, within-subject crossover study.

As the study uses a within-subject crossover design all participants will recieve all conditions for that group. The group is determined by the participants opioid medication (one of three groups, methadone, buprenorphine or healthy control. Healthy controls are recieiving neither methadone not buprenorphine).
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple computer generated randomization to determine the order of the conditions is conducted by the PI who has no other role in data collection so the remaining study staff can remain blinded to the study condition). The randomisation is communiacted to the off site clinical trials pharmacist who makes up the medications (active and placebo) for each session, so the blind can be maintained by the study staff.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Phase 3 / Phase 4
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
5/03/2010
Actual
5/03/2010
Date of last participant enrolment
Anticipated
Actual
15/07/2017
Date of last data collection
Anticipated
Actual
13/08/2017
Sample size
Target
36
Accrual to date
Final
21
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment postcode(s) [1] 5066 0
2050
Recruitment postcode(s) [2] 5067 0
2010
Recruitment postcode(s) [3] 5068 0
2165

Funding & Sponsors
Funding source category [1] 284835 0
Government body
Name [1] 284835 0
Mental Health Drug and Alcohol Office (MHDAO)
Country [1] 284835 0
Australia
Primary sponsor type
Hospital
Name
Sydney Local Health District - Royal Prince Alfred Hospital
Address
Post Office Box M30
Missenden Road NSW 2050
Country
Australia
Secondary sponsor category [1] 283713 0
Hospital
Name [1] 283713 0
South Eastern Sydney Local Health District - Langton Centre
Address [1] 283713 0
Langton Centre
591 South Dowling St
Surry Hills 2010
Country [1] 283713 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 286825 0
Sydney Local Health District Ethics Review Committee (RPAH Zone)
Ethics committee address [1] 286825 0
Ethics committee country [1] 286825 0
Australia
Date submitted for ethics approval [1] 286825 0
Approval date [1] 286825 0
30/06/2009
Ethics approval number [1] 286825 0
HREC/09/RPA/160

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

Contacts
Principal investigator
Name 33873 0
Dr Bridin Murnion
Address 33873 0
Royal Prince Alfred Hospital
Department of Addiction Medicine
Missenden Road
Camperdown 2050
New South Wales
Country 33873 0
Australia
Phone 33873 0
+61 2 95157611
Fax 33873 0
Email 33873 0
bridin.murnion@sydney.edu.au
Contact person for public queries
Name 17120 0
Dr Bridin Murnion
Address 17120 0
Drug Health Services, Building 73, Concord Repatriation Hospital, Hospital Road, Concord NSW 2139
Country 17120 0
Australia
Phone 17120 0
+ 61 2 9767 8320
Fax 17120 0
+ 61 2 9767 8327
Email 17120 0
bmurnion@med.usyd.edu.au
Contact person for scientific queries
Name 8048 0
Dr Bridin Murnion
Address 8048 0
Drug Health Services, Building 73, Concord Repatriation Hospital, Hospital Road, Concord NSW 2139
Country 8048 0
Australia
Phone 8048 0
+ 61 2 9767 8320
Fax 8048 0
+ 61 2 9767 8327
Email 8048 0
bmurnion@med.usyd.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


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
No additional documents have been identified.