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Trial registered on ANZCTR


Registration number
ACTRN12617000126314
Ethics application status
Approved
Date submitted
18/01/2017
Date registered
24/01/2017
Date last updated
6/03/2019
Date data sharing statement initially provided
6/03/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Investigating exercise based interventions for elbow pain.
Scientific title
What is the effect of two different muscle contraction types on pain in patients with lateral epicondylalgia?
Secondary ID [1] 290682 0
None
Universal Trial Number (UTN)
Trial acronym
ISOLATE - ISOmetric exercise for LATeral Epicondylalgia
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Lateral epicondylalgia 301218 0
Condition category
Condition code
Musculoskeletal 300976 300976 0 0
Other muscular and skeletal disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants will complete only one phase of the trial, and will be randomised as to whether they receive 1a or 1b, or 2a or 2b first. Each intervention involves a single session, taking approximately 90 minutes. Each session will be conducted by a physiotherpist (chief investigator). There will be a 1 week washout period between interventions.


Phase 1: Intervention (1a): Isometric wrist extension exercise 5 x 45 secs with 2 minute rest between repetitions.

Phase 2: Intervention (2a): Superior isometric exercise protocol as determined after phase 1 performed 5 x 45 secs with 2 minute rest between repetitions.
If after phase 1 no difference is shown between isometric protocols, the cheif investigator will make an a priori decision as to which exercise will be selected as for intervention 2a in phase 2)
Intervention code [1] 296566 0
Treatment: Other
Comparator / control treatment
Phase 1: Intervention (1b): Isometric wrist extension and supination exercise 5 x 45 secs with 2 minute rest between repetitions. This exercise is different to 1a as it combines extension and supination movements (2 directions of motion)

Phase 2: Intervention (2b): Isotonic exercise matched to intervention 2a above for time under tension and load.

Control group
Active

Outcomes
Primary outcome [1] 300402 0
Pain will be measured on a Numerical Rating Scale (o-10, where 0 equals no pain and 10 equals the worst possible pain), during a provocation test (resisted 3rd finger extension).
Timepoint [1] 300402 0
Pain will be measured
-immediately following the performed intervention
-30 minutes after the performed intervention
-60 minutes after the performed intervention
Secondary outcome [1] 329888 0
Maximum grip strength will be measured in wrist neutral with the elbow at 90 degrees, using a grip strength dynamometer. The participant will be instructed to squeeze the dynamometer as hard as they possibly can. 3 attempts will be made, and the average of these recorded.
Timepoint [1] 329888 0
Grip strength will be measured
-immediately following the performed intervention
-30 minutes after the performed intervention
-60 minutes after the performed intervention
Secondary outcome [2] 329889 0
Pain will be measured on a Numerical Rating Scale (o-10, where 0 equals no pain and 10 equals the worst possible pain), during maximal grip strength testing using a grip strength dynamometer.
Timepoint [2] 329889 0
Pain during maximal grip strength will be measured:
-immediately following the performed intervention
-30 minutes after the performed intervention
-60 minutes after the performed intervention
Secondary outcome [3] 330314 0
Transcranial Magnetic Stimulation (TMS) to measure corticospinal excitability.
Timepoint [3] 330314 0
TMS testing will be carried out immediately following the completion of the exercise intervention.
Secondary outcome [4] 330958 0
Transcranial Magnetic Stimulation (TMS) to measure short interval cortical inhibition (SICI).
Timepoint [4] 330958 0
TMS testing will be carried out immediately following the completion of the exercise intervention.
Secondary outcome [5] 330959 0
Transcranial Magnetic Stimulation (TMS) to measure long interval cortical inhibition (LICI).
Timepoint [5] 330959 0
TMS testing will be carried out immediately following the completion of the exercise intervention.

Eligibility
Key inclusion criteria
Participants will be screened by researchers, and included if a diagnosis of current lateral epicondylalgia is confirmed, defined as - self reported localised pain over the common extensor origin at the lateral epicondyle with a loading task such as resisted 3rd digit extension. The loading task must be related to high intensity loading, as opposed to low load repetitive task (such as using a mouse/keyboard).
Minimum age
18 Years
Maximum age
70 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
General Exclusions:
Any neurological symptoms including numbness, pins and needles or weakness
Past history of elbow surgery
Past history of cervical spine surgery
Psychiatric illness
Inability to speak, read or write English

TMS Exclusions:
Brain injury or any surgery to the brain (ie. metal implants in head/brain, outside the mouth)
Any metallic particles in the eye
Aneurysm clips
Cochlear implants
Noise induced hearing loss
Pace makers / spinal cord stimulators
Epilepsy of history of seizure activity (or family history in first degree relatives)

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)
Randomly drawn opaque envelopes. Assessors and data analysts will be blinded to participant allocation. Participants and researchers carrying out the intervention will be unable to be blinded.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation will occur generated by a random number generator in an excel spreadsheet. Randomisation will occur in blocks.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Crossover
Other design features
This study will be a two phase randomised trial, with a cross-over model.
Phase 1: 25 participants will be randomised as to whether they receive the phase 1 intervention or phase 1 comparator arm first. Subjects will complete the other arm one week later to allow for a wash out period.

Phase 2: A further 25 participants will be randomised as to whether they will receive the phase 2 intervention or phase 2 comparator arm first. Subjects will complete the other intervention one week later to allow for a wash out period.
Phase
Type of endpoint/s
Statistical methods / analysis
Data will be analysied by a single analyst blinded to the participant's intervention, and which timepoint is being analysed.
All data will be screened with the Shapiro-Wilk test, and if found to be normally distributed
means and standard deviations will be used, using one way ANOVA and post hoc t-test. A split-plot in time-repeated measures ANOVA will be used to compare the effect of each intervention on pain and grip strength. For non-normally distributed data the median and range will be used and data evaluated using the equivalent non parametric test (Kruskall Wallis), significance will be set at 0.05.

Recruitment
Recruitment status
Withdrawn
Reason for early stopping/withdrawal
Lack of funding/staff/facilities
Participant recruitment difficulties
Date of first participant enrolment
Anticipated
1/03/2017
Actual
Date of last participant enrolment
Anticipated
1/03/2019
Actual
Date of last data collection
Anticipated
8/03/2019
Actual
Sample size
Target
50
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
TAS,VIC

Funding & Sponsors
Funding source category [1] 295110 0
University
Name [1] 295110 0
La Trobe University
Country [1] 295110 0
Australia
Primary sponsor type
University
Name
La Trobe University
Address
La Trobe University
Plenty Road & Kingsbury Drive
Bundoora VIC 3086
Country
Australia
Secondary sponsor category [1] 293929 0
None
Name [1] 293929 0
Address [1] 293929 0
Country [1] 293929 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 296462 0
La Trobe University Human Research Ethics Comittee
Ethics committee address [1] 296462 0
La Trobe University
Plenty Road & Kingsbury Drive
Bundoora VIC 3086
Ethics committee country [1] 296462 0
Australia
Date submitted for ethics approval [1] 296462 0
07/12/2016
Approval date [1] 296462 0
08/03/2017
Ethics approval number [1] 296462 0
HEC17-008

Summary
Brief summary
Lateral epicondylalgia (tendinopathy of the wrist extensors at the lateral epicondyle) is a common condition seen in middle aged people, and despite this, best management is poorly understood. Isometric exercises have been shown as effective in treating tendinopathies in the lower limb, however no-one has investigated the impact of different exercise protocols on immediate pain in the upper limb, and thus for lateral epicondylalgia. A two part cross-over study will examine whether different isometric protocols have better results on pain in this condition, and whether the superior isometric exercise is better than isotonic exercise for immediate impact on lateral epicondylalgia.
Trial website
Trial related presentations / publications
Public notes
TMS Protocol:
Baseline measures of corticospinal excitability, SICI and LICI will be obtained using single-pulse and paired-pulse TMS, respectively. The accuracy of TMS will be optimised by aligning the coil with reference markers on a tight fitting cap worn by participants and marked with a latitude–longitude matrix, positioned with reference to the nasion-inion and interaural lines.

Single-pulse stimulus-response curves (corticospinal excitability) will be obtained during low-level isometric contractions of the wrist extensor muscle group. Low-level contractions will be performed by contracting the wrist extensors maintaining the wrist in neutral while performing a 10% MVIC, which equates to 5±1% of root mean square (RMS) electromyography (rmsEMG) during MVIC. A 10% isometric muscle contraction is a non-painful task for someone with lateral epicondylalgia. Consistent muscle activation will be confirmed by recording pre-stimulus rmsEMG throughout the session. For a single stimulus-response curve, 10 stimuli will be delivered in 20% increments from 90% of the participant's active motor threshold (AMT) up to 190% of their AMT. The stimuli will be delivered using a ramped protocol. The amplitude of the motor-evoked potential (MEP) or slope of the stimulus-response curve represents corticospinal excitability.

SICI and LICI are probed by providing a subthreshold stimulus that activates inhibitory interneurons that synapse onto pyramidal neurons in the M1 and results in reduced number of action potentials by the subsequent suprathreshold stimulus. To quantify inhibition, 10 single-pulse stimuli and 10 short-interval paired-pulse stimuli will be delivered in random counterbalanced order. Intensity will be set at 120% of AMT, which will be determined during familiarisation and adjusted if there is a change in AMT. The conditioning stimulus for paired-pulse stimulation will be set at 80% of AMT, the interstimulus interval will be 3 ms to test SICI and 150ms to test LICI, and posterior to anterior current flow will be used to induce I3 waves. SICI and LICI are represented as a percentage ratio where high levels of inhibition are indicated by a low ratio. Therefore, an increase in the SICI or LICI percentage represents a reduction in inhibition.

Participants will be tested at the same time of day and the same day of the week. TMS will be delivered using two Magstim 200 2 stimulators connected via a Bistim unit (Magstim Co, Dyfed, UK) and a 110 mm concave double-cone coil (maximum output of 1.4 T). The motor hotspot for the extensor muscle (with posterior-induced to anterior-induced current flow in the cortex) will be determined and AMT will be established as the intensity at which at least 5 of 10 stimuli produced MEP amplitudes of greater than 200 µV recorded from the extensor muscle. Valid EMG data for the forearm can be captured with surface electrodes.

The area of electrode placement will be shaved to remove fine hair, rubbed with an abrasive skin rasp to remove dead skin, and then cleaned with 70% isopropyl alcohol. Bipolar gel Ag-AgCl electrodes (8 mm diameter, model E258S; Biopac, Goleta, California, USA) will be placed over the extensor muscle (centre–centre interelectrode distance=2 cm). A grounding electrode strap will be placed over the wrist and subsequently used as a common reference for all electrodes. All cables will be fastened with tape to prevent movement artefact. The location of electrodes will be marked with a permanent marker by tracing around the electrode, and measured from ulnar styloid to lateral epicondyle to maximise consistency of electrode placement relative to the innervation zone. An impedance metre will be used to check that impedance does not exceed 10 kO prior to testing. Surface EMG (sEMG) signals will be amplified (×1000), bandpass filtered (high pass at 13 Hz, low pass at 1000 Hz), digitised online at 2 kHz for 500 ms, recorded and analysed using PowerLab 4/35 (ADInstruments, Bella Vista, Australia).

Pre-stimulus rmsEMG activity will be determined in the muscle, 100 ms prior to each TMS stimulus during pretesting and post-testing. Any trial in which prestimulus rmsEMG exceeds 5±1% of maximal rmsEMG will be discarded and the trial repeated. The surface rmsEMG will be calculated from a 500 ms segment that occurred during the asymptote of each maximal voluntary contraction (MVC) and was calculated as the amplitude of the RMS value.

Contacts
Principal investigator
Name 70942 0
Dr Ebonie Rio
Address 70942 0
La Trobe Sport and Exercise Medicine Research Centre
La Trobe University
Plenty Road & Kingsbury Drive
Bundoora VIC 3086
Country 70942 0
Australia
Phone 70942 0
+61 3 9479 3785
Fax 70942 0
Email 70942 0
e.rio@latrobe.edu.au
Contact person for public queries
Name 70943 0
Ebonie Rio
Address 70943 0
La Trobe Sport and Exercise Medicine Research Centre
La Trobe University
Plenty Road & Kingsbury Drive
Bundoora VIC 3086
Country 70943 0
Australia
Phone 70943 0
+61 3 9479 3785
Fax 70943 0
Email 70943 0
e.rio@latrobe.edu.au
Contact person for scientific queries
Name 70944 0
Ebonie Rio
Address 70944 0
La Trobe Sport and Exercise Medicine Research Centre
La Trobe University
Plenty Road & Kingsbury Drive
Bundoora VIC 3086
Country 70944 0
Australia
Phone 70944 0
+61 3 9479 3785
Fax 70944 0
Email 70944 0
e.rio@latrobe.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
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.