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Trial registered on ANZCTR


Registration number
ACTRN12619001069145
Ethics application status
Approved
Date submitted
18/07/2019
Date registered
31/07/2019
Date last updated
12/02/2021
Date data sharing statement initially provided
31/07/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
The effect of aerobic exercise on pain in people with diabetic neuropathy
Scientific title
The effect of a single bout of moderate-intensity aerobic on pain thresholds in people with diabetic neuropathy: a randomised controlled crossover trial
Secondary ID [1] 298769 0
None
Universal Trial Number (UTN)
U1111-1237-1726
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Diabetic neuropathy 313708 0
Condition category
Condition code
Metabolic and Endocrine 312121 312121 0 0
Diabetes
Neurological 312200 312200 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The intervention will involve a single bout of aerobic exercise on a stationary cycle ergometer (Monark 928 G3). The intervention will be delivered face-to-face on an individual basis by an undergraduate Exercise Physiology student under the supervision of an Accredited Exercise Physiologist. The exercise bout will commence with a 5-minute warmup at low intensity (approximately 40% of the participant's age-predicted maximum heart rate), followed by 15 minutes of moderate intensity exercise (60-70% of participant's age-predicted maximum heart rate). After the warm up, participants will be encouraged to exercise at 70% of their age-predicted maximum heart rate for the remaining duration of the exercise bout, but will be allowed to exercise at intensities as low as 60% of their age-predicted maximum heart rate if needed. On this basis, the intervention will be tailored to each individual. At the end of the warm up, and then every 5 minutes during exercise, the participant's heart rate, blood pressure and rating of perceived exertion (Borg 6-20 scale) will be recorded. The exercise bout will end with a 2-3 minute cool down at low intensity (rating of perceived exertion 8-9/20). The entire experimental session will last up to 120 minutes depending on whether or not it is performed first in the crossover design. If performed first, the rest of the experimental session will consist of assessments of pressure pain threshold before and after exercise (15 min), monitoring of the participant for any adverse signs/symptoms following exercise (up to 60 min), completion of questionnaires relating to the participants' health and level of physical activity (20 min), and provision of an accelerometer (Actigraph wGT3X-WT) (5 min) which will be used to measure the participant's physical activity levels for one week following the first session. If performed second, the experimental session will last up to 90 minutes as the questionnaires and accelerometer procedures will not be performed. All testing will be performed in the Exercise Physiology laboratories at UNSW Sydney
Intervention code [1] 315036 0
Lifestyle
Intervention code [2] 315170 0
Treatment: Other
Comparator / control treatment
The comparator treatment will be sham exercise. Sham exercise will utilise a 20 min bout of very gentle exercise against minimal resistance on a stationary cycle ergometer (Monark 928 G3), Participants will be asked to pedal at a level that elicits a rating of perceived exertion of 6-7 on the Borg 6-20 scale (i.e. very very light). Sham exercise will be delivered face-to-face on an individual basis by an undergraduate Exercise Physiology student under the supervision of an Accredited Exercise Physiologist. Every 5 minutes during sham exercise, the participant's heart rate, blood pressure and rating of perceived exertion (Borg 6-20 scale) will be recorded. The entire experimental session will last up to 120 minutes depending on whether or not it is performed first in the crossover design. If performed first, the rest of the experimental session will consist of assessments of pressure pain threshold before and after exercise (15 min), monitoring of the participant following sham exercise (up to 60 min), completion of questionnaires relating to the participants' health and level of physical activity (20 min), and provision of an accelerometer (Actigraph wGT3X-WT) (5 min) which will be used to measure the participant's physical activity levels for one week following the first session. If performed second, the experimental session will last up to 90 minutes as the questionnaires and accelerometer procedures will not be performed. All testing will be performed in the Exercise Physiology laboratories at UNSW Sydney
Control group
Active

Outcomes
Primary outcome [1] 320764 0
Change in pressure pain threshold assessed using a handheld algometer (Wagner FDX 50)
Timepoint [1] 320764 0
Immediately prior to exercise/sham exercise and immediately following exercise/sham exercise
Primary outcome [2] 320765 0
Change in heat pain threshold assessed using a contact thermode (Medoc TSA II NeuroSensory Analyzer)
Timepoint [2] 320765 0
Within 10 minutes prior to the start of exercise/sham exercise and within 10 minutes following exercise/sham exercise
Primary outcome [3] 320829 0
Change in cold pain threshold assessed using a contact thermode (Medoc TSA II NeuroSensory Analyzer)
Timepoint [3] 320829 0
Within 10 minutes prior to the start of exercise/sham exercise and within 10 minutes following exercise/sham exercise
Secondary outcome [1] 372762 0
Physical activity levels measured using an accelerometer (Actigraph wGT3x-BT)
Timepoint [1] 372762 0
During the 7 days following the first experimental session
Secondary outcome [2] 372763 0
Self-reported neuropathic pain assessed using the painDETECT questionnaire
Timepoint [2] 372763 0
During the enrolment visit which will occur within one month of the participant attending the laboratory for their first experimental session.
Secondary outcome [3] 372764 0
Neuropathy severity according to the Total Neuropathy Score - a validated tool employing standard, non-invasive neurological assessments including symptom report, peripheral sensation, strength tests and nerve conduction studies.
Timepoint [3] 372764 0
During the enrolment visit which will occur within one month of the participant attending the laboratory for their first experimental session.
Secondary outcome [4] 372765 0
Self-reported pain measured using the McGill Pain Questionnaire
Timepoint [4] 372765 0
During the enrolment visit which will occur within one month of the participant attending the laboratory for their first experimental session.
Secondary outcome [5] 372766 0
Self-reported physical activity measured using the short-version of the International Physical Activity Questionnaire
Timepoint [5] 372766 0
During the enrolment visit which will occur within one month of the participant attending the laboratory for their first experimental session.

Eligibility
Key inclusion criteria
Participants will be males and females aged 18-65 with a diagnosis of Type 2 diabetes mellitus and evidence of neuropathy according to the Total Neuropathy Score (Grades 0-4). Participants must also be able to speak, read and write in English.
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Unable to speak, read or write in English or provide informed consent
2. History of hypoglycaemia unawareness
3. Uncontrolled diabetes or hospitilisation from ketoacidosis or hypoglycaemia in the month prior to testing
4. Women lactating, pregnant or of childbearing potential who are not willing to avoid becoming pregnant during the study.
4. Have received neuromodulatory medication within the last month.
5. Have received/currently receiving an investigatory drug within the last 3 months.
6. Symptoms or signs that are contraindications to exercise and have not been cleared by their physician for exercise will be excluded from randomisation to exercising groups. However, these individuals will still invited to complete questionnaires and undergo 7 days of accelerometer-based physical activity monitoring

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)
This is a randomised cross-over study. Each participant will receive exercise or sham exercise, but the order of these will be randomised and concealed (by opaque envelopes) to the participant and study coordinator.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software (i.e. computerised sequence generation)
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
Sample size calculation:
This study will be the first to explore the relationship between acute exercise and physical activity levels on pain in people with diabetic neuropathy. As such, a sample size calculation for all outcomes was not possible. A previous study utilising similar methodology (Knauf & Koltyn, 2014) found a small effect (Cohen’s d = 0.42) of exercise on reducing pain in people with diabetic neuropathy. Assuming this same small effect, 39 participants are needed to detect a change of this size with alpha of 0.05 and 80% power. Associations between physical activity and pain are typically moderate (Pearson’s r = 0.4) in people with chronic pain (Jones et al, 2016). Assuming a similar strength association between physical activity and pain in people with diabetic neuropathy, 46 participants are required to detect an association between physical activity and pain with alpha = 0.05 and 80% power. Therefore, at least 46 participants are required to appropriately power this study. However, to account for the possibility of participant drop out, we intend to recruit 50 participants.

Statistical analysis:
Data will be analysed using the IBM Statistical Package for Social Sciences (Version 25). A two-way repeated measures analysis of variance (ANOVA) will be used to investigate changes in pain threshold after exercise/sham exercise (time: pre, post; condition: exercise, sham exercise). For significant effects, Bonferroni corrected paired sample t-tests will be performed post hoc to identify the source of differences revealed by ANOVA. Effects sizes (Cohen's d) with 95% confidence intervals will also be calculated to aid comparisons between the different effects of exercise and sham exercise on pain thresholds. The association(s) between physical activity with pain and neuropathy severity will be assessed using Pearson's correlation and linear regression. For all statistical tests, significance for alpha will be set to p < 0.05.

Recruitment
Recruitment status
Withdrawn
Reason for early stopping/withdrawal
Lack of funding/staff/facilities
Date of first participant enrolment
Anticipated
5/08/2019
Actual
Date of last participant enrolment
Anticipated
3/08/2020
Actual
Date of last data collection
Anticipated
31/08/2020
Actual
Sample size
Target
50
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 14249 0
Prince of Wales Hospital - Randwick
Recruitment postcode(s) [1] 27246 0
2031 - Randwick

Funding & Sponsors
Funding source category [1] 303325 0
Hospital
Name [1] 303325 0
Prince of Wales Hospital
Country [1] 303325 0
Australia
Funding source category [2] 303384 0
University
Name [2] 303384 0
University of New South Wales
Country [2] 303384 0
Australia
Primary sponsor type
University
Name
University of New South Wales
Address
University of New South Wales,
Sydney, NSW, Australia
2052
Country
Australia
Secondary sponsor category [1] 303350 0
None
Name [1] 303350 0
Address [1] 303350 0
Country [1] 303350 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 303859 0
South Eastern Sydney Local Health District Human Research Ethics committee
Ethics committee address [1] 303859 0
Ethics committee country [1] 303859 0
Australia
Date submitted for ethics approval [1] 303859 0
Approval date [1] 303859 0
02/04/2019
Ethics approval number [1] 303859 0

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

Contacts
Principal investigator
Name 95046 0
Prof Arun Krishnan
Address 95046 0
Prince of Wales Clinical School,
Edmund Blacket Building,
Prince of Wales Hospital,
Randwick, NSW, 2031
Country 95046 0
Australia
Phone 95046 0
+61 2 9382 2414
Fax 95046 0
Email 95046 0
arun.krishnan@unsw.edu.au
Contact person for public queries
Name 95047 0
Matthew Jones
Address 95047 0
Wallace Wurth Building
Department of Exercise Physiology, School of Medical Sciences
UNSW Sydney
Kensington, NSW 2052
Country 95047 0
Australia
Phone 95047 0
+61 2 9385 3375
Fax 95047 0
Email 95047 0
matthew.jones@unsw.edu.au
Contact person for scientific queries
Name 95048 0
Matthew Jones
Address 95048 0
Wallace Wurth Building
Department of Exercise Physiology, School of Medical Sciences
UNSW Sydney
Kensington, NSW 2052
Country 95048 0
Australia
Phone 95048 0
+61 02 9385 3375
Fax 95048 0
Email 95048 0
matthew.jones@unsw.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
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.