Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622000642785
Ethics application status
Approved
Date submitted
19/04/2022
Date registered
3/05/2022
Date last updated
6/02/2023
Date data sharing statement initially provided
3/05/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
Effect of Exercise on Individuals with Chronic Neck Pain and Central Sensitisation
Scientific title
Ability of clinical measures of central sensitisation to predict effectiveness of exercise in individuals with chronic neck pain
Secondary ID [1] 306569 0
Nil Known
Universal Trial Number (UTN)
U1111-1275-1994
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Neck Pain 325466 0
Central Sensitisation 325520 0
Condition category
Condition code
Musculoskeletal 322846 322846 0 0
Other muscular and skeletal disorders
Neurological 322847 322847 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This study is a randomised crossover trial, investigating the effect of a single-bout (30 minutes) of high intensity sub-maximal aerobic cycling exercise versus a low intensity aerobic cycling exercise. Intensity of exercise is determined by the a priori criteria of age-predicted max heart rate. High intensity exercise will have a targeted 75% age-predicted max heart rate, and low intensity will have a target of 50% age-predicted max heart rate. Intervention will be delivered in a face-to-face supervised setting, by a researcher with a background in clinical exercise physiologist with 5 years experience. Participants will attend two sessions of assessments with a 1-2 week 'washout' period between each session. The study will be conducted at the Physiotherapy Rehabilitation Gym located at The University of Adelaide.
Intervention code [1] 323000 0
Rehabilitation
Comparator / control treatment
As this study follows the randomised crossover trial design, there is no 'control' group. The comparison will be high intensity versus low intensity aerobic cycling exercise.
Control group
Dose comparison

Outcomes
Primary outcome [1] 330775 0
Exercise-induced hypoalgesia (EIH). EIH will be assessed through pain pressure threshold (PPT) measurement, followed by a fatigue-inducing exercise stimulus, and lastly, the same PPT measurements. PPT will be measured using Echo Wireless Algometer (JTECH Medical, Utah, United States). PPT will be measured at two sites; (1) over the C5/6 spinous process in the cervical spine, and (2) over the muscle belly of the left tibialis anterior. To ensure accurate measurement, a ‘x’ will be marked on the testing site with a marker during baseline assessment, the same site will be used for post-exercise PPT assessment. Pressure will be applied on the testing site at a rate of approximately 5 N/s. Participants will be asked to verbally state when the sensation change from “comfortable” pressure to “unpleasant” pain sensation. Triplicate reading, with a 30s interstimulus interval, will be taken at each site and the mean values will be used for analysis. PPT measures will be taken prior to and following the fatigue-inducing exercise stimulus. The fatigue-inducing exercise stimulus will be an isometric wall-squat. Participants will be asked to maintain in a wall-squat position until fatigue or for a maximum of 3-mins.
Timepoint [1] 330775 0
Baseline
Immediately post-exercise
Primary outcome [2] 331170 0
Temporal Summation (TS). TS will be induced using a 256mN punctate needle stimulator or “PinPrick” (MRC Systems GmbH, Heidelberg, Germany) as the noxious stimuli, at two sites: (1) over the C5/6 spinous process in the cervical spine, and (2) dorsal surface of the dominant hand between the second and third metacarpals. A ‘x’ will be marked at the testing site to ensure accuracy for baseline and post-exercise assessment. In the test, a single stimulus will first be applied, participants will be instructed to verbally rate the pain intensity. Then after a period of 10s, a series of ten identical punctate stimuli will be applied at a frequency of 1Hz, which has been shown to be sufficient to induce TS. The participant will verbally state the pain rating immediately following the last stimulus. A printed numerical pain rating scale (NPRS), labelled with digits from 0 to 10, with ‘0’ indicating ‘no pain’ and ‘10’ being ‘extremely painful’, will be displayed in front of the participant.
Timepoint [2] 331170 0
Baseline
Immediately post-exercise
Primary outcome [3] 331171 0
Conditioned pain modulation (CPM). CPM will be measured using PPT as the test stimulus and cold pressor test as the conditioning stimulus. PPT will be measured using Echo Wireless Algometer (JTECH Medical, Utah, United States). The baseline PPT (PPTbase) is obtained from EIH assessment. The participants will be instructed to immerse their non-dominant hand in an ice-bath (up to the wrist), and will be motivated through verbal encouragement to maintain immersion for the duration of the defined period of 120s. Participants are instructed to verbally state when he/she began to feel pain. Cold pain threshold is the time, in seconds, that passed between the immersion and the verbal confirmation of pain sensation. Cold pressor pain tolerance is the total time, in seconds, in immersion. Single PPT will be measured over the previously marked site on the tibialis anterior, at 30s, 60s, 90s, and at the time of cold pain threshold occurring during immersion.
Timepoint [3] 331171 0
Baseline
Immediately post-exercise
Secondary outcome [1] 407515 0
Lactate concentration ([La]). [La] will be analysed using Lactate Scout 4 lactate analyser (SensLab GmbH, Leipzig, Germany). A drop of blood obtained using a single-use lancing device on the fingertip, will be required for analysis. To ensure accuracy in measurement, manufacturer’s protocol guideline will be followed.
Timepoint [1] 407515 0
Baseline
Immediately post-exercise

Eligibility
Key inclusion criteria
*Chronic neck pain (3/10 pain NPRS rating)
*Chronic neck pain duration >12 weeks
*Age 19 to 65 years old
Minimum age
19 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
*Known or suspected serious spinal pathology (e.g. metastatic, inflammatory or infective disease of the spine
*Confirmed fracture or dislocation at the time of injury
*Nerve root compromise (at least 2 of the following symptoms: weakness/reflex changes/sensory loss associated with the same spinal nerve)
*Spinal surgery in the previous 12 months
*History or presentation of psychosis, bipolar disorder, organic brain disorder or severe depression
*Were taking anti-depressant or anticonvulsant 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)
A researcher not involved in the study will carry out the randomisation using the website www.randomizer.org. The sequence generated will be written on a card, and concealed in a sealed opaque envelope.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation will be performed using a online website www.randomizer.org. Block randomisation will be performed.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
For this clinical trial, the sample size is calculated based on pain pressure threshold. To our knowledge, as there is no data on aerobic exercise testing with similar intervention groupings in chronic non-specific neck pain, the a priori power analysis was conducted based on data from an exercise intervention study with similar intervention grouping. The sample size of this study is calculated based on difference in mean pain pressure thresholds between two different exercise intervention, a desired two-tailed, a=0.05, ß=0.80, and an allocation ratio of 1:1. The calculations revealed that 64 participants would be sufficient, however to allow a loss to follow-up of 20% and conservative approach, total of 80 participants with chronic neck pain will be recruited.

All data will be analyzed via scatterplots, boxplots and Kolmogorov-Smirnov statistics to evaluate normality. Normally distributed data will be reported as means and SD. Other data will be reported as median and interquartile range (IQR). Parametric test will be used to analyze group differences for normally distributed data, and non-parametric tests will be used for between-group differences for physical outcome measures and baseline questionnaires and physical measures.

To rule out carryover effects, the sum of the measured values in the sessions for each patient will be calculated and compared across the two groups by an unpaired t-test36. A p-value of >0.05 indicates no carryover effects, and the “washout” duration is sufficient. To determine statistical difference between HIGH versus LOW, within-subject difference in outcome parameters between both sessions will be calculated using Student’s unpaired t-test. If there is a statistical significance, a regression model will be conducted to evaluate the effect of exercise intensity (HIGH vs. LOW) on CS measures. The fixed effect of time (baseline and post exercise), exercise intensity, and study group were included in the model, with age as a covariate. If no statistical difference was detected, repeated measurement analysis of variance (ANOVA) will be performed to assess significant difference between both groups, within-subject factor will be defined as “time” and “group” as between-subject factor. Significance level will be adjusted by the number of comparisons using Bonferroni correction.

Multivariate regression analysis will be used to analyse the association between [La] and CS outcome measures. In order to examine the relationship between individual measures of CS (EIH, CPM and TS), separate regressions will be conducted. Models will be adjusted for age, sex, education level, physical activity level, NDI, PCS, and TSK. Statistical significance is set at p<0.05.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/08/2022
Actual
26/08/2022
Date of last participant enrolment
Anticipated
30/11/2023
Actual
Date of last data collection
Anticipated
30/12/2023
Actual
Sample size
Target
80
Accrual to date
7
Final
Recruitment in Australia
Recruitment state(s)
SA

Funding & Sponsors
Funding source category [1] 310902 0
University
Name [1] 310902 0
The University of Adelaide
Country [1] 310902 0
Australia
Primary sponsor type
Individual
Name
Dr Rutger de Zoete
Address
School of Allied Health Science and Practice
The University of Adelaide
Adelaide, South Australia 5005
Country
Australia
Secondary sponsor category [1] 312187 0
Individual
Name [1] 312187 0
Prof Mark Hutchinson
Address [1] 312187 0
School of Allied Health Science and Practice
The University of Adelaide
Adelaide, South Australia 5005
Country [1] 312187 0
Australia
Secondary sponsor category [2] 312352 0
Individual
Name [2] 312352 0
Prof Paul Rolan
Address [2] 312352 0
School of Allied Health Science and Practice
The University of Adelaide
Adelaide, South Australia 5005
Country [2] 312352 0
Australia
Secondary sponsor category [3] 312675 0
Individual
Name [3] 312675 0
Kexun Kenneth Chen
Address [3] 312675 0
The University of Adelaide
Adelaide, South Australia, 5000
Country [3] 312675 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 310464 0
University of Adelaide Human Research Ethics Committee
Ethics committee address [1] 310464 0
Ethics committee country [1] 310464 0
Australia
Date submitted for ethics approval [1] 310464 0
14/04/2022
Approval date [1] 310464 0
01/06/2022
Ethics approval number [1] 310464 0
H-2022-082

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

Contacts
Principal investigator
Name 117754 0
Dr Rutger de Zoete
Address 117754 0
School of Allied Health Science and Practice
The University of Adelaide
Adelaide, SA 5005
Country 117754 0
Australia
Phone 117754 0
+61 08 831 33034
Fax 117754 0
Email 117754 0
[email protected]
Contact person for public queries
Name 117755 0
Rutger de Zoete
Address 117755 0
School of Allied Health Science and Practice
The University of Adelaide
Adelaide, SA 5005
Country 117755 0
Australia
Phone 117755 0
+61 08 831 33034
Fax 117755 0
Email 117755 0
[email protected]
Contact person for scientific queries
Name 117756 0
Rutger de Zoete
Address 117756 0
School of Allied Health Science and Practice
The University of Adelaide
Adelaide, SA 5005
Country 117756 0
Australia
Phone 117756 0
+61 08 831 33034
Fax 117756 0
Email 117756 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
data collected will be de-identified. data will include all outcome measures collected.
When will data be available (start and end dates)?
Data will be available immediately following publication, and ending 5 years following main results publication.
Available to whom?
It will be available to public
Available for what types of analyses?
meta-analysis
How or where can data be obtained?
Data will be published on an online repository, Figshare.


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
15439Study protocol    Link to protocol will be listed once published.



Results publications and other study-related documents

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

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseEffect of exercise on chronic neck pain and central sensitization: A protocol for a randomized crossover trial.2023https://dx.doi.org/10.1113/EP091065
N.B. These documents automatically identified may not have been verified by the study sponsor.