Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12619000629134
Ethics application status
Approved
Date submitted
18/04/2019
Date registered
29/04/2019
Date last updated
13/01/2022
Date data sharing statement initially provided
29/04/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
The effects of physical exercise on the brain and the immune system in individuals with chronic pain.
Scientific title
The Central Neurobiological and Immunological Effects of Exercise in Individuals with Chronic Pain.
Secondary ID [1] 296516 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Whiplash Associated Disorder 310299 0
Chronic Pain 312556 0
Condition category
Condition code
Musculoskeletal 309030 309030 0 0
Other muscular and skeletal disorders
Neurological 311075 311075 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants will be randomised into a staggered baseline of 5, 8, 11, or 14 days. In order to gain an understanding of the variability in clinical outcomes, during this baseline phase three daily questions will assess pain intensity, pain bothersomeness, and disability. The eight-week exercise intervention commences following the completion of the staggered baseline. Through randomisation, participants will be allocated to either the aerobic exercise (intervention) or resistance exercise (comparator) program. Both eight-week programs follow the American College for Sports Medicine Guidelines for Exercise Testing and Prescription.

Aerobic: For the aerobic exercise program, participants will engage in three exercise sessions per week of at least 20 min, focussing on self-chosen, whole-body exercises such as walking, cycling, etc. The target intensity is 40-60% of maximum heart rate (MHR = 220-age) and will be determined using a heart rate monitor (the participant will be provided with one for the study). Participants are asked to refrain from resistance training for the duration of the study.

The total duration of participation in this study is the baseline duration (5, 8, 11, 14 days) + 8 weeks of exercise intervention. For both study arms, adherence to the exercise intervention will be monitored with weekly phone calls.
Intervention code [1] 312827 0
Rehabilitation
Comparator / control treatment
The comparator is the resistance exercise group:

Participants in the resistance exercise group will engage in three exercise sessions per week, approximately 30 minutes per session. Although no standardised program will be followed, the focus of the exercises will be on strengthening of monoarticular muscle groups away from the neck. Examples of possible resistance exercises are: upper extremities exercises including biceps curl, triceps extension, seated row, lower extremities exercises including squad, lunge, wall sit, calf raises. Training will be performed in 2-3 sets per exercise, and the chosen resistance allows for 8-12 repetitions with proper form per set. The target intensity for each exercise is 40-60% of the 1-repeated maximum (the resistance with which someone can correctly perform one repetition of the exercise). Participants in the resistance exercise group will be provided with a Gymstick in order to perform the exercises. Participants will be asked to refrain from aerobic exercises they would not have normally done for the duration of the study.
Control group
Active

Outcomes
Primary outcome [1] 307990 0
Pain intensity (0-100 numeric rating scale [NRS], 0=no pain, 100=worst pain imaginable)
Timepoint [1] 307990 0
Assessed daily in the baseline phase, and daily in the intervention phase, with primary time point being 8 weeks after the start of the exercise intervention. This will be used to determine the effect of the intervention.
Primary outcome [2] 319861 0
Pain interference (0-100 NRS, 0=no interference, 100=extreme interference)
Timepoint [2] 319861 0
Assessed daily in the baseline phase, and daily in the intervention phase, with primary time point being 8 weeks after the start of the exercise intervention. This will be used to determine the effect of the intervention.
Primary outcome [3] 319862 0
Disability (Short Form Health Survey (SF-36) question, scored 1-100, 1=not at all, 100=extremely)
Timepoint [3] 319862 0
Assessed daily in the baseline phase, and daily in the intervention phase, with primary time point being 8 weeks after the start of the exercise intervention. This will be used to determine the effect of the intervention.
Secondary outcome [1] 353580 0
o Exercise-induced effects on pain:
- Pressure Pain Threshold before and after 20 min exercise session
Timepoint [1] 353580 0
Secondary outcome measures are assess three times: At baseline, after 4 weeks of exercise intervention, and after 8 weeks of exercise intervention. The 8-week follow-up data will be used to determine the effect of the intervention.
Secondary outcome [2] 369737 0
o Sensorimotor control
- Joint position error test
Timepoint [2] 369737 0
Secondary outcome measures are assess three times: At baseline, after 4 weeks of exercise intervention, and after 8 weeks of exercise intervention. The 8-week follow-up data will be used to determine the effect of the intervention.
Secondary outcome [3] 369738 0
o Neurological outcomes (magnetic resonance [MR]):
- Functional connectivity (resting state functional MRI [rs-MRI])
Timepoint [3] 369738 0
Secondary outcome measures are assess three times: At baseline, after 4 weeks of exercise intervention, and after 8 weeks of exercise intervention. The 8-week follow-up data will be used to determine the effect of the intervention.
Secondary outcome [4] 369739 0
o Concentrations of immunological biomarkers
- Blood derived neurotrophic factor (BDNF)
Timepoint [4] 369739 0
Secondary outcome measures are assess three times: At baseline, after 4 weeks of exercise intervention, and after 8 weeks of exercise intervention. The 8-week follow-up data will be used to determine the effect of the intervention.

Eligibility
Key inclusion criteria
Inclusion criteria – WAD
- Chronic whiplash associated disorder (>12 weeks duration)
- Aged between 18 and 55 years
o The lower age limit of 18 years will be applied as the brain in children is still in development which could potentially affect the MR outcomes. An upper age limit of 55 years will be applied to limit the possible effect of degenerative changes in the aging brain.
- Moderate neck pain intensity (at least 4/10 on a 0-10 numeric rating scale)
- Pain moderately interferes with daily activities (assessed using one item* from the SF-36 questionnaire)
- Currently low level of physical activity (assessed with the Godin-Shephard activity questionnaire)
- Motivated to commit to an eight-week exercise program
- Able to lie in an MRI scanner on their back for one hour
- Free from metal implants or pacemaker
* During the past 4 weeks, how much did pain interfere with your normal work (including both work outside the home and housework)?


Inclusion criteria – healthy controls
- No current neck pain, nor having had treatment for neck/shoulder complaints in the past 5 years
- No history of injury or trauma to the neck or head
- No current musculoskeletal pain in any body area
- Aged between 18 and 55 years
o The lower age limit of 18 years will be applied as the brain in children is still in development which could potentially affect the MR outcomes. An upper age limit of 55 years will be applied to limit the possible effect of degenerative changes in the aging brain.
- Currently low level of physical activity (assessed with the Godin-Shephard activity questionnaire)
- Motivated to commit to an eight-week exercise program
- Able to lie in an MRI scanner on their back for one hour
- Free from metal implants or pacemaker
- Matched to an individuals with WAD based on sex and age
Minimum age
18 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Exclusion criteria – WAD and healthy individuals
- History of migraine headaches
- Surgery to the neck
- Diabetes
- Posttraumatic stress symptoms (assessed on the PCL-5)
o Individuals with substantial posttraumatic stress symptoms will be excluded from this study as psychological stress may interfere with adherence to the exercise program,58 the neurobiological effects of exercise, and the effects of exercise on health outcomes.
- Currently receiving treatment for their neck pain (e.g., physiotherapy, chiropractic, or similar)
- Comorbidities preventing regular exercise
- Pregnant or breastfeeding
- Claustrophobic

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 with only a number on the outside of the envelope will guarantee allocation concealment.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Participants will be randomised twice: (1) to determine the length of the staggered baseline phase (5, 8, 11, or 14 days), and (2) to determine the type of eight-week exercise intervention (aerobic/resistance). Permuted block randomisation will be used to ensure balance across treatment groups. Both randomisation processes will be performed with a custom written script in MatLab.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Descriptive and group baseline data will be analysed using the SPSS package. Intervention effects will be statistically analysed using the single-case randomisation, a test specifically designed (for the R package) for the analysis of data from SCED studies. As visual analysis is an important part of SCED data analysis, pain intensity, pain perception, and disability outcomes will be visually analysed by graphing daily outcomes for the duration of the baseline and intervention.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
20/05/2019
Actual
3/06/2019
Date of last participant enrolment
Anticipated
1/10/2019
Actual
1/10/2019
Date of last data collection
Anticipated
31/12/2019
Actual
31/12/2019
Sample size
Target
16
Accrual to date
Final
16
Recruitment in Australia
Recruitment state(s)
QLD

Funding & Sponsors
Funding source category [1] 301755 0
Government body
Name [1] 301755 0
NHMRC
Country [1] 301755 0
Australia
Primary sponsor type
University
Name
The University of Queensland
Address
The University of Queensland
St Lucia, 4072, QLD Australia
Country
Australia
Secondary sponsor category [1] 302503 0
None
Name [1] 302503 0
Address [1] 302503 0
Country [1] 302503 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 301854 0
Royal Brisbane and Women's Hospital Human Research Ethics Committee
Ethics committee address [1] 301854 0
Ethics committee country [1] 301854 0
Australia
Date submitted for ethics approval [1] 301854 0
14/02/2019
Approval date [1] 301854 0
26/03/2019
Ethics approval number [1] 301854 0
Ethics committee name [2] 303230 0
The University of Queensland Human Research Ethics Committee
Ethics committee address [2] 303230 0
Ethics committee country [2] 303230 0
Australia
Date submitted for ethics approval [2] 303230 0
26/03/2019
Approval date [2] 303230 0
15/04/2019
Ethics approval number [2] 303230 0
2019000769

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

Contacts
Principal investigator
Name 88326 0
Dr Rutger de Zoete
Address 88326 0
288 Herston Rd
Oral Health Building
The University of Queensland
QLD 4006
Country 88326 0
Australia
Phone 88326 0
+61 733464787
Fax 88326 0
Email 88326 0
[email protected]
Contact person for public queries
Name 88327 0
Rutger de Zoete
Address 88327 0
288 Herston Rd
Oral Health Building
The University of Queensland
QLD 4006
Country 88327 0
Australia
Phone 88327 0
+61 733464787
Fax 88327 0
Email 88327 0
[email protected]
Contact person for scientific queries
Name 88328 0
Rutger de Zoete
Address 88328 0
288 Herston Rd
Oral Health Building
The University of Queensland
QLD 4006
Country 88328 0
Australia
Phone 88328 0
+61 733464787
Fax 88328 0
Email 88328 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
No individual participant data will be available in order to assure confidentiality.


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
1131Ethical approval    376317-(Uploaded-18-04-2019-15-42-33)-Study-related document.pdf



Results publications and other study-related documents

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

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseThe effects of physical exercise on structural, functional, and biochemical brain characteristics in individuals with chronic whiplash-associated disorder: A pilot randomized clinical trial.2023https://dx.doi.org/10.1111/papr.13240
N.B. These documents automatically identified may not have been verified by the study sponsor.