Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12618000967280p
Ethics application status
Submitted, not yet approved
Date submitted
24/05/2018
Date registered
8/06/2018
Date last updated
6/02/2019
Date data sharing statement initially provided
6/02/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
The role of skeletal muscle and immediate pain responses to muscle strengthening exercises in knee osteoarthrits
(The AsPIRE study)
Scientific title
The role of skeletal muscle and determinants of Altered Pain threshold responses with acute Resistance Exercise in knee osteoarthrits
(The AsPIRE study)
Secondary ID [1] 294935 0
Nil Known
Universal Trial Number (UTN)
U1111-1214-3724
Trial acronym
AsPIRE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Knee Osteoarthritis 307908 0
Condition category
Condition code
Musculoskeletal 306948 306948 0 0
Osteoarthritis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The intervention is resistance exercise in a randomized cross-over trial design.

The study will involve 3 study visits. Study visit 1 will involve an invitation to complete self-assessment questionnaires, physical and clinical assessments, familiarization with the leg press machine, pain pressure threshold procedure and a 1-repetition maximum (1-RM) test. Participants will undergo a 1-repetition maximum test (1-RM) to test the maximum weight a participant can lift in a single repetition, for the leg-press exercise.

Participants will be randomized to perform 3 sets of either high-intensity or low-intensity resistance exercise during Study Visit 2 using a seated leg-press exercise machine, as determined from their 1-RM test from Study Visit 1. High-intensity leg press exercises will be performed at 75%-85% of 1-RM for 3 sets of 8 repetitions, whereas low-intensity leg-press exercises will be performed at 30-40% of 1-RM for 3 sets of 15 repetitions. During the final study visit (Study Visit 3), the subject will perform the alternative resistance exercise. The minimum washout period between the study visits is 10 days. Pain pressure threshold and immediate mood assessments will be performed before and after leg-press exercises.

Study visit 1 is estimated to take around 4 hours, whereas study visits 2 and 3 are estimated to take around 2 hours.
Participants will be requested to perform a 5-minute period of warm-up which will consist of either walking or stationary cycling before their leg strength measurements and the leg-press exercises.

The exercise intervention will be delivered individually face-to-face, by the principal investigator who is a physician.
Intervention code [1] 301284 0
Treatment: Other
Comparator / control treatment
AsPIRE is a randomized cross-over study with an exercise intervention undertaken during 3 study visits in participants with early and late knee OA.
The study participants act as their own control in a cross-over study design, receiving high-intensity resistance exercise and low-intensity resistance exercise with a wash-out period of 10-14 days in between interventions.

The comparator in this study is the low-intensity leg-press exercises which will be performed at 30-40% of 1-RM for 3 sets of 15 repetitions.
Control group
Active

Outcomes
Primary outcome [1] 305976 0
Change in pain pressure threshold (PPT) before and after high-intensity and low-intensity resistance exercise as determined by a hand-held pressure algometer
Timepoint [1] 305976 0
PPT will be measurement within 5 minutes after completing the 3rd set of resistance exercise. Baseline PPT will be measured within 5 minutes before commencing the 1st set of resistance exercise.
Secondary outcome [1] 347162 0
Change in immediate mood before and after high-intensity and low-intensity resistance exercise. Immediate mood is assessed using a 12-item questionnaire, the Immediate Mood Scaler (IMS-12)
Timepoint [1] 347162 0
Immediate mood will be measurement within 5 minutes after completing the 3rd set of resistance exercise. Baseline mood will be measured within 5 minutes before commencing the 1st set of resistance exercise.
Secondary outcome [2] 347705 0
Skeletal muscle mRNA expression of myokines assessed by laboratory analysis of muscle tissue biopsy
Timepoint [2] 347705 0
Muscle tissue biopsy is planned to be performed in participants with end-stage knee OA, during their usual total knee arthroplasty surgery.

Eligibility
Key inclusion criteria
1. For the early knee OA group, subjects should be diagnosed as having knee OA using the Kellgren-Lawrence grade(KLG) grade, with KLG 1-2 as a criteria on plain radiograph of the knee.
2. For the late knee OA group, subjects should be diagnosed as having knee OA using the Kellgren-Lawrence grade (KLG) grade, with KLG 4 as a criteria on plain radiograph of the knee. The additional criteria for participants in the late knee OA group is that they should be scheduled for total knee arthroplasty
3. Able to complete questionnaires in English
4. Able and willing to complete study assessments
5. Able and willing to provide written consent to participate in the study
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Documented history of systemic inflammatory or autoimmune diseases
• Documented history of skeletal muscle pathological diseases such as myopathies and myositis
• History of diabetes, significant cardiovascular, neurological or psychiatric disease, cervical or lumbar root compression syndromes and widespread regional pain syndromes (e.g. fibromyalgia)
• History of lower extremity joint replacement in the study limb
• Women who are pregnant or lactating or of child-bearing potential who are not willing to avoid pregnancy during the study period
• Systolic Blood pressure > 200mmHg and / or diastolic blood pressure > 120mmHg
• Current use of oral steroid medications
• Unable to discontinue non-steroidal anti-inflammatory medication use

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)
Allocation to high- or low-intensity resistance exercise of eligible participants will be concealed using sealed opaque envelopes prepared by a person not involved in the study.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Participants will be assigned to either a high-intensity or low-intensity acute resistance exercise for study visit 2 with a 1:1 allocation as per a computer-generated randomisation schedule using random blocks of size 4 and 6. The participants will be performing the alternative intensity of resistance exercise during study visit 3.
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
A total sample size of 48 patients (24 in each sequence) provides at least 80% power to detect a difference of 1.5 units (assuming standard deviations of 3 for each exercise regimen) in pressure pain threshold (minimum detectable change considered real(1) between the low and high intensity exercise regimens using a 0.05 significance level. This sample size calculation assumes that each pair of measurements on the same subject will have a correlation of about 0.3. The study will include 24 participants with severe knee OA and 24 participants with mild-moderate knee OA.


Primary study question analysis
Paired t-test will be performed to compare the change in PPT measures (pre- and post-) resistance exercise between high- and low-intensity resistance exercise sessions
A repeated measures model will be used to adjust for covariates

Secondary Study Questions:
i. A repeated measures model including a treatment by severity interaction term alongside the main effects of treatment and severity will be used to compare the effect of treatment in each severity of knee OA group
ii. Linear regression will be used to examine the relationship between baseline pain levels and the change in PPT after acute resistance exercise separately for high and low intensities. This will be initially examined together and then separately for the mild and severe groups.
iii. A GEE model will be used to examine the relationship between baseline inflammatory cytokines with the change in PPT (before and after exercise) for acute high and low intensity resistance exercises. This will be examined separately for the mild and severe groups.
iv. A GEE model will be used to examine whether skeletal muscle fiber-type, expression of cytokine and nerve growth factor is related to the change in PPT (before and after exercise) for acute high and low intensity resistance exercises. This will be examined separately for the mild and severe groups.
v. ANOVA will be used to compare levels of expression of muscle-derived myokines between types of muscle fibres. Boxplots will be shown for graphical display.

Recruitment
Recruitment status
Withdrawn
Reason for early stopping/withdrawal
Other reasons/comments
Other reasons
Conversion of PhD degree to a MPhil
Date of first participant enrolment
Anticipated
1/07/2018
Actual
Date of last participant enrolment
Anticipated
31/05/2019
Actual
Date of last data collection
Anticipated
30/06/2019
Actual
Sample size
Target
48
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 10957 0
Royal North Shore Hospital - St Leonards
Recruitment postcode(s) [1] 22743 0
2065 - St Leonards

Funding & Sponsors
Funding source category [1] 299520 0
Other Collaborative groups
Name [1] 299520 0
British Association of Sport & Exercise Medicine
Country [1] 299520 0
United Kingdom
Primary sponsor type
University
Name
University of Sydney
Address
Higher Degree by Research Administration Centre
G02, Jane Foss Russell Building,
Level 5, The University of Sydney,
160 City Rd,
Darlington NSW 2008,
Australia
Country
Australia
Secondary sponsor category [1] 298819 0
None
Name [1] 298819 0
Address [1] 298819 0
Country [1] 298819 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 300417 0
Northern Sydney Local Health District Human Research Ethics Committee
Ethics committee address [1] 300417 0
Ethics committee country [1] 300417 0
Australia
Date submitted for ethics approval [1] 300417 0
26/03/2018
Approval date [1] 300417 0
Ethics approval number [1] 300417 0

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

Contacts
Principal investigator
Name 83594 0
Dr Priathashini Krishnasamy
Address 83594 0
Level 7C, Clinical Administration,
Department of Rheumatology
Royal North Shore Hospital
St Leonards 2065
New South Wales, Australia
Country 83594 0
Australia
Phone 83594 0
+61 2 94631888
Fax 83594 0
Email 83594 0
[email protected]
Contact person for public queries
Name 83595 0
Priathashini Krishnasamy
Address 83595 0
Level 7C, Clinical Administration,
Department of Rheumatology
Royal North Shore Hospital
St Leonards 2065
New South Wales, Australia
Country 83595 0
Australia
Phone 83595 0
+61 2 94631888
Fax 83595 0
Email 83595 0
[email protected]
Contact person for scientific queries
Name 83596 0
Priathashini Krishnasamy
Address 83596 0
Level 7C, Clinical Administration,
Department of Rheumatology
Royal North Shore Hospital
St Leonards 2065
New South Wales, Australia
Country 83596 0
Australia
Phone 83596 0
+61 2 94631888
Fax 83596 0
Email 83596 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
Trial has been withdrawn


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.