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Trial registered on ANZCTR


Trial ID
ACTRN12613000840785
Ethics application status
Approved
Date submitted
17/06/2013
Date registered
30/07/2013
Date last updated
8/05/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
A randomized, blinded, comparator-controlled trial investigating a 28-day course of Lyrica in participants with knee osteoarthritis who exhibit neuropathic pain, compared with a 28-day course of acetaminophen.
Scientific title
A randomized, blinded, comparator-controlled trial investigating a 28-day course of Lyrica in participants with knee osteoarthritis who exhibit neuropathic pain, compared with a 28-day course of acetaminophen.
Secondary ID [1] 282688 0
NIL
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Osteoarthritis 289402 0
Condition category
Condition code
Musculoskeletal 289725 289725 0 0
Osteoarthritis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This study aims to investigate whether the neuropathic pain medication pregabalin (Lyrica) is more effective than standard paracetamol in relieving pain and widespread neuropathic-type symptoms in individuals with mild to moderately painful knee osteoarthritis, who have been assessed for the additional presence of neuropathic pain.
Participants will be randomly allocated to take either Lyrica (intervention) and placebo paracetamol (sugar pills) or 1000mg paracetamol four times daily (active control) and placebo Lyrica (sugar pills) daily for 28 days. The Lyrica dose will be titrated from 75mg daily to a potential maximum of 150mg over 14 days, dependent on individual tolerance level. All medications are to be taken orally.
All patients will be issued with a medication diary in which clear instructions are provided for titrating medications. In addition to this, patients will receive regular telephone calls to ensure titration instructions are understood and adhered to. Research staff will work very closely with patients in this area.
Note: Patients will be required to complete the medication diary with the number of tablets taken on each day. This will be returned at the end of the study along with any unused medication. At this point drug accountability will be performed by research staff before returning to Pharmacy, who will also monitor drug accountability.

Intervention code [1] 287348 0
Treatment: Drugs
Comparator / control treatment
Participants on the active control arm will be prescribed 1000mg paracetamol four times daily and placebo Lyrica for the duration of the study which is 28 days. Both the paracetamol and placebo Lyrica will need to be taken orally.
Control group
Active

Outcomes
Primary outcome [1] 289815 0
Cold Detection and Cold Pain Threshold (CDT & CPT) at index knee to assess cold hyperalgesia.

This outcome is measured using a Peltier thermode. The thermode probe is attached to the test site with a velcro strap and subjects given time to adapt to the baseline temperature of 32C. When the device is activated the thermode temperature will drop at a rate of 1C/sec. Subjects will be instructed to depress the hand-held switch as soon as they perceive any cooling change from baseline. The endpoint measure is the thermode temperature (C) at first perceived cooling change from baseline. The thermode then returns to the baseline temperature. For cold pain threshold testing, subjects will be instructed to press the switch as soon as the cooling sensation changes to one of painful cold, thereby reversing the temperature to baseline. The endpoint measure is the thermode temperature on first indicated painful cold. For both CDT and CPT, one practice will be followed by 3 trials, each trial separated by a randomly assigned pause of between 3 and 6 seconds. The mean of the trials will be calculated for analysis.
Timepoint [1] 289815 0
28 Days
Primary outcome [2] 289816 0
Pressure Pain Threshold (PPT) at index knee to assess mechanical hyperalgesia.

This outcome will be measured using a digital pressure algometer. The 1cm2 algometer probe is applied at a 90 degree angle to the skin at a rate of rise of applied pressure of 40kPa/sec. Subjects are instructed to depress the hand-held switch as soon as the sensation of pressure becomes one of painful pressure. The endpoint measure is the pressure value (kPa/cm2) when the subject indicates painful pressure. One practice followed by 3 trials, with the mean calculated for analysis.
Timepoint [2] 289816 0
28 Days
Primary outcome [3] 289817 0
Self Reported Clinical Measures using The Western Ontario and McMaster Universities Arthritis Index (WOMAC) Pain subscore & PainDETECT scores.

WOMAC will be used to evaluate subjective pain, stiffness and functional limitation at each test session. This OA-specific self-report scale is widely used to measure pain and disability from knee OA.

Pain DETECT Neuropathic Pain Diagnostic Questionnaire is a validated self report tool and will be used to identify neuropathic pain components in subjects within this study.
Timepoint [3] 289817 0
28 Days
Secondary outcome [1] 303294 0
Cold Detection & Cold Pain Threshold (CPT), Pressure Pain Threshold (PPT) and cold response at other sites (widespread hyperalgesia).

This outcome will be measured using the same methods that will be employed to assess the 1st and 2nd primary outcomes. However instead of assessing only the knees for signs of cold hyperalgesia, other sites will be assessed. This includes the forearm (extensor carpi radialis brevis) and lower leg (tibialis anterior).
Timepoint [1] 303294 0
28 Days
Secondary outcome [2] 303295 0
Vibration Detection Threshold (VDT) - will be assessed using a Vibrameter. The device will be applied at a standard pressure equivalent to th eprobe weight (650g) and the vibration amplitude will be gradually increased to the point where the subject indicates they perceive the vibration - VPT. The device will then be activated at a higher amplitude and the amplitude will be gradually decreased to the point where the stimulus is no longer felt - vibration disappearance threshold (VDT). One practice and three trials will be carried out for each measure.
Timepoint [2] 303295 0
28 Days
Secondary outcome [3] 303296 0
The Western Ontario and McMaster Universities Arthritis Index (WOMAC) Questionnaire will be used to evaluate subjective pain, stiffness and functional limitation at each test session. This OA-specific self-report scale is widely used to measure pain and disability from knee OA
Timepoint [3] 303296 0
28 Days
Secondary outcome [4] 303297 0
Physical function as a secondary outcome will be measured using Aggregated Locomotor Function Score.
Timepoint [4] 303297 0
28 Days
Secondary outcome [5] 303946 0
Quality of Life will be measured with the SF-36v2, a generic self-reported health outcomes assessment tool. The tool measures general health status via eight domains, including mental health, general health perceptions and physical functioning, generating either sub-scores or a total score of health outcome.
Timepoint [5] 303946 0
28 Days
Secondary outcome [6] 303947 0
The Pain Quality Assessment Scale (PQAS) Questionnaire will be used to provide data regarding the dimensions of spontaineous pain experienced by OA subjects. Subjects will complete the PQAS at each test session in order to assess the effect of the medication on specific sub-scales which reflect different pain domains.
Timepoint [6] 303947 0
28 Days

Eligibility
Key inclusion criteria
Unilateral diagnosis of knee OA greater than 6 months duration, according to the American College of Rheumatology clinical classification system (diagnosis performed by an experienced Rheumatologist (Dr Will) based on radiological & clinical presentation); Pain in the index knee greater than or equal to 4 out of 10 with an additional 1-1.5 out of 10 increase in pain on walking when withdrawn from their usual analgesic medication; No additional clinically significant joint involvement and otherwise in good health; American Rheumatology Association functional Class I, II or III; No recent arthroscopy, injections with glucocorticoid or hyaluronan in last 6 months to index knee; No plan for joint replacement surgery during the study period.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
History of other systemic inflammatory conditions; neurological deficits (motor, cognitive or sensory); recent lower limb injury or surgery (< 6 months); history of other chronic pain disorders (eg fibromyalgia); skin allergies; history of allergic reaction to pregabalin / gabapentin / acetaminophen; ASA of IV; severe hepatic dysfunction (serum albumin <25g/l); congestive heart failure; chronic renal failure; pregnancy; breast feeding;
compromised creatinine clearance (<30mL/min); hereditary
problems with galactose metabolism; History of severe depression or currently on medication for depression or anxiety.

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)
Randomisation will be carried out using a computer program available only to the study Pharmacists located off site, with all other study staff blinded to the subject group allocation. Coded drug supplies will be dispensed in the Royal Perth Hospital (RPH) Pharmacy. In order to ensure full blinding, all subjects will receive a package that includes an appropriate dosage of the active medication and a placebo formulation of the alternate medication.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
A computer programme will generate a randomisation table. Only the RPH Pharmacy staff will have access to this randomisation table until all data collection and analysis has been completed
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
The people analysing the results/data
Intervention assignment
Other design features
Phase
Type of endpoint(s)
Statistical methods / analysis
It is estimated that from previous studies that in order to achieve a power of 80%, based on a clinically significant change in primary outcomes of 20% the study will require approx. 45 subjects per group, with a total cohort of 90 subjects.
Clinically significant change has been calculated as an approximate 15-20% improvement from baseline mean. To detect a 20% change from baseline, a sample size of between 38 and 51 would be needed per group.

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)
WA

Funding & Sponsors
Funding source category [1] 287460 0
Commercial sector/Industry
Name [1] 287460 0
Pfizer Australia
Address [1] 287460 0
38-42 Wharf Rd, West Ryde NSW 2114
Country [1] 287460 0
Australia
Primary sponsor type
Individual
Name
Dr Robert Will
Address
Royal Perth Hospital
197 Wellington Street
Perth WA 6000
Country
Australia
Secondary sponsor category [1] 286204 0
None
Name [1] 286204 0
Address [1] 286204 0
Country [1] 286204 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 289435 0
Royal Perth Hospital Human Ethics Committee
Ethics committee address [1] 289435 0
Royal Perth Hospital
197 Wellington Street
Perth WA 6000
Ethics committee country [1] 289435 0
Australia
Date submitted for ethics approval [1] 289435 0
Approval date [1] 289435 0
16/04/2013
Ethics approval number [1] 289435 0
REG 13-005

Summary
Brief summary
This study aims to investigate whether the neuropathic pain medication pregabalin (Lyrica) is more effective than standard paracetamol in relieving pain and widespread neuropathic-type symptoms in individuals with mild to moderately painful knee osteoarthritis, who have been assessed for the additional presence of neuropathic pain.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 40838 0
Prof Anthony Wright
Address 40838 0
Curtin University, School of Physiotherapy, Building 408, Kent Street, Bentley WA 6102
Country 40838 0
Australia
Phone 40838 0
+618 9266 4644
Fax 40838 0
Email 40838 0
T.Wright@curtin.edu.au
Contact person for public queries
Name 40839 0
Ms Lisa Webster
Address 40839 0
Rob K Will Pty. Ltd., 27/443 Albany Highway, Victoria Park WA 6100
Country 40839 0
Australia
Phone 40839 0
+61437778110
Fax 40839 0
Email 40839 0
lmwebster@bigpond.com
Contact person for scientific queries
Name 40840 0
Ms Penny Moss
Address 40840 0
Curtin University, School of Physiotherapy, Building 408, Kent Street, Bentley WA 6102
Country 40840 0
Australia
Phone 40840 0
+618 9266 3668
Fax 40840 0
Email 40840 0
P.Moss@curtin.edu.au