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Trial registered on ANZCTR


Registration number
ACTRN12618001366246
Ethics application status
Approved
Date submitted
27/07/2018
Date registered
14/08/2018
Date last updated
14/08/2018
Type of registration
Retrospectively registered

Titles & IDs
Public title
Repetitive transcranial magnetic stimulation in preventing the transition from acute to sustained pain: A randomised controlled trial
Scientific title
Repetitive transcranial magnetic stimulation in preventing the transition from acute to sustained pain: A randomised controlled trial
Secondary ID [1] 295676 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Mechanical hyperalgesia 309033 0
Pain 309214 0
Functional disability 309215 0
Muscle soreness 309232 0
Condition category
Condition code
Neurological 307927 307927 0 0
Studies of the normal brain and nervous system
Musculoskeletal 308088 308088 0 0
Other muscular and skeletal disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This study involved 8 experimental sessions across a 14-day period (Day -2, 0, 2, 4, 6, 8, 11, and 14). Progressive muscle soreness and mechanical hyperalgesia are induced via repeated NGF injections. A 5 µg (0.2 mL) bolus of recombinant human NGF is injected into the muscle belly of the right ECRB using a 1 ml syringe and disposable 27G needle. Injections are administered at the end of the test sessions on Days 0, 2, and 4. The injection site is located 1cm lateral and 5cm distal to the origin of a line extending from the lateral epicondyle to the midline of the wrist crease. One experimenter administers all injections.

The intervention is high frequency repetitive transcranial magnetic stimulation (rTMS) applied to the motor cortex (the ‘hotspot’) region dedicated to the right ECRB using a Magstim Super Rapid2 (Magstim Co. Ltd, Dyfed, UK) and a 70mm air cooled figure-of-eight coil. A total of 1200 stimuli are delivered at a frequency of 10 Hz, in 20 trains of 6 seconds (54-second inter-train interval). Stimuli are delivered at 90% of the participant's resting motor threshold. Active or sham rTMS are delivered following repeated intramuscular injections. Each rTMS session takes approximately 20 minutes. The rTMS protocol consists of one session per day for 5 consecutive days (Days 4, 5, 6, 7, and 8), with rTMS being delivered after all assessments are performed. Stimuli are delivered by the chief investigator, who is familiar with the use of TMS. A second researcher is present to monitor the participant and the fidelity of the intervention. The chief investigator's supervisors provide support outside of the lab.


Intervention code [1] 301991 0
Treatment: Devices
Comparator / control treatment
For sham rTMS, the coil is held at 90 degrees relative to the skull , rather than tangentially, to direct the magnetic field away from cortical tissue and mimic the active condition.
Control group
Placebo

Outcomes
Primary outcome [1] 306900 0
Mechanical hyperalgesia (measured using pressure pain thresholds). Pressure is applied perpendicular to the surface of the skin using a handheld algometer (Somedic, 1 cm2 probe) at a rate of 30 kPa/s. The PPT is defined as the point at which the participant reported that a sensation of pressure first changed to a sensation of pain (refs). Three readings are recorded at 1-minute intervals. The average of the three measures is used during statistical analyses.
Timepoint [1] 306900 0
Days 6, 8 (primary time point), 11, and 14 (post-rTMS commencement). Assessments are also taken on Days 0, 2 and 4 (pre-rTMS commencement).
Primary outcome [2] 306901 0
Pain and disability measured using the Patient Rated Tennis Elbow Evaluation (PRTEE)
Timepoint [2] 306901 0
Days 6, 8 (primary time point), 11, and 14 (post-rTMS commencement). Assessments are also taken on Days 0, 2 and 4 (pre-rTMS commencement).
Primary outcome [3] 306902 0
Transcranial Magnetic Stimulation (TMS) motor cortical maps.
Timepoint [3] 306902 0
Days 6, 8 (primary time point), 11, and 14 (post-rTMS commencement). Assessments are also taken on Days 0, 2 and 4 (pre-rTMS commencement).
Secondary outcome [1] 350052 0
Muscle Soreness (in the ECRB muscle) on a 7-point Likert Scale.
Timepoint [1] 350052 0
Days 6, 8, 11, and 14 (post-rTMS commencement). Assessments are also taken on Days 0, 2 and 4 (pre-rTMS commencement).
Secondary outcome [2] 350053 0
Pain area and distribution (body charts). (composite outcome)
Timepoint [2] 350053 0
Days 6, 8, 11, and 14 (post-rTMS commencement). Assessments are also taken on Days 0, 2 and 4 (pre-rTMS commencement).
Secondary outcome [3] 350055 0
Conditioned pain modulation (CPM). In this study, the average of three PPT recordings over the right ECRB represented the test stimulus. Immersion of the left hand in temperature-controlled ice water (4-6oC) was used as the conditioning stimulus. Pressure pain thresholds were recorded prior to cold immersion and following 1 minute of immersion, with the difference in PPT recordings being used to quantify the CPM effect.
Timepoint [3] 350055 0
Days 6, 8, 11, and 14 (post-rTMS commencement). Assessments are also taken on Days 0, 2 and 4 (pre-rTMS commencement).

Eligibility
Key inclusion criteria
-Healthy
-No previous exposure to repetitive transcranial magnetic stimulation (rTMS)
- Able to understand and speak English
Minimum age
20 Years
Maximum age
50 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
-Failure to pass the Transcranial Magentic Stimulation Safety Screen questionnaire
-Cardiovascular disorders
-Use of neuroactive drugs
-Pregnancy
-History of neurological illness
-History of musculoskeletal illness
-Previous exposure to rTMS
-Contraindications to rTMS or TMS
-Current acute pain or recent musculoskeletal injury
-History of chronic pain

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)
Sealed opaque envelopes
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a computerised random number generator
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


Intervention assignment
Parallel
Other design features
Phase
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
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] 300260 0
University
Name [1] 300260 0
Western Sydney University
Address [1] 300260 0
Narellan Rd & Gilchrist Dr, Campbelltown NSW 2560
Country [1] 300260 0
Australia
Primary sponsor type
University
Name
Western Sydney University
Address
Western Sydney University, Campbelltown Campus, Narellan Rd & Gilchrist Dr, Campbelltown NSW 2560
Country
Australia
Secondary sponsor category [1] 299683 0
None
Name [1] 299683 0
NA
Address [1] 299683 0
NA
Country [1] 299683 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 301078 0
Western Sydney University Human Research Ethics Comittee
Ethics committee address [1] 301078 0
Human Ethics Officer
Research Engagement, Development and Innovation (REDI)
Western Sydney University
Locked Bag 1797
Penrith NSW 2751
Ethics committee country [1] 301078 0
Australia
Date submitted for ethics approval [1] 301078 0
24/09/2016
Approval date [1] 301078 0
07/11/2016
Ethics approval number [1] 301078 0
H11896

Summary
Brief summary
The purpose of this study is to i) determine whether a 5-day block of high frequency rTMS, delivered to the motor cortex, can be used to treat the pain, mechanical hyperalgesia, and disability associated with repeated intramuscular injection of human nerve growth factor (NGF) and ii) determine whether a 5-day block of high frequency rTMS, delivered to the motor cortex, reduces the motor cortical changes associated with the transition from acute to sustained pain. Three injections of NGF will be delivered and active or sham rTMS will commence 4 days post-injection.

prevent the transition from acute to sustained pain associated with repeated intramuscular injection of human nerve growth factor (NGF).
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 85806 0
Mr Rocco Cavaleri
Address 85806 0
Western Sydney University, Campbelltown Campus, Narellan Rd & Gilchrist Dr, Campbelltown NSW 2560
Country 85806 0
Australia
Phone 85806 0
+61 2 4620 3994
Fax 85806 0
Email 85806 0
R.cavaleri@westernsydney.edu.au
Contact person for public queries
Name 85807 0
Mr Rocco Cavaleri
Address 85807 0
Western Sydney University, Campbelltown Campus, Narellan Rd & Gilchrist Dr, Campbelltown NSW 2560
Country 85807 0
Australia
Phone 85807 0
+61 2 4620 3994
Fax 85807 0
Email 85807 0
R.cavaleri@westernsydney.edu.au
Contact person for scientific queries
Name 85808 0
Mr Rocco Cavaleri
Address 85808 0
Western Sydney University, Campbelltown Campus, Narellan Rd & Gilchrist Dr, Campbelltown NSW 2560
Country 85808 0
Australia
Phone 85808 0
+61 2 4620 3994
Fax 85808 0
Email 85808 0
R.cavaleri@westernsydney.edu.au

No data has been provided for results reporting
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary