Trial Review

Registering a new trial?

To achieve prospective registration, we recommend submitting your trial for registration at the same time as ethics submission.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12613000467730
Ethics application status
Approved
Date submitted
22/04/2013
Date registered
24/04/2013
Date last updated
24/04/2013
Type of registration
Retrospectively registered

Titles & IDs
Public title
The pathogenesis of muscle inflammation in knee osteoarthritis and its effect on gait and muscle function
Scientific title
The pathogenesis of muscle inflammation in people with knee osteoarthritis who undergo knee replacement surgery and its effect on gait and muscle function
Secondary ID [1] 282385 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Knee osteoarthritis 288966 0
Condition category
Condition code
Musculoskeletal 289302 289302 0 0
Osteoarthritis

Intervention/exposure
Study type
Observational
Patient registry
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
Muscle tissue of the vastus lateralis, synovial fluid from the knee joint, synovium and blood will be collected from people with severe knee osteoarthritis during their knee replacement surgery.
Knee replacement surgery is a surgical procedure in which the severely damaged knee joint is replaced with an artificial joint.
Intervention code [1] 287017 0
Not applicable
Comparator / control treatment
Asymptomatic age matched controls

For the control group only muscle tissue and blood will be sampled.
The muscle from the 20 aged- and BMI-matched asymptomatic individuals (control group) will be collected by needle biopsy (under local anaesthetic).
Control group
Active

Outcomes
Primary outcome [1] 289410 0
Inflammatory markers in the muscle
The muscle tissue will be separated into a fraction that will be mounted for IHC analysis (presence of inflammatory cells), protein analysis (analysis of inflammatory factors, including cytokines and chemokines; extracellular matrix proteins and intra-muscular stress pathways.
Specific markers of muscle atrophy and inflammation including mRNA abundance for pro-inflammatory and catabolic cytokines genes encoding proteins linked to atrogenesis will be assessed using standard real time RT-PCR and western blotting techniques
Timepoint [1] 289410 0
Cross sectional, only one point: sample will be collected during knee replacement surgery
Primary outcome [2] 289411 0
Inflammatory markers in the synovial fluid

Specific markers of muscle atrophy and inflammation including mRNA abundance for pro-inflammatory and catabolic cytokines genes encoding proteins linked to atrogenesis will be assessed using standard real time RT-PCR and western blotting techniques
Timepoint [2] 289411 0
Cross sectional, only one point: sample will be collected during knee replacement surgery
Primary outcome [3] 289429 0
Inflammatory markers in the serum

Specific markers of muscle atrophy and inflammation including mRNA abundance for pro-inflammatory and catabolic cytokines genes encoding proteins linked to atrogenesis will be assessed using standard real time RT-PCR and western blotting techniques
Timepoint [3] 289429 0
Cross sectional design - samples will be taken once during the surgery
Secondary outcome [1] 302418 0
Gait -
Qualitative gait analysis will include the use of three dimenational (3D) motion analysis system (VICON, Oxford Metrics).
Timepoint [1] 302418 0
Cross sectional, one point: prior knee replacement surgery
Secondary outcome [2] 302453 0
Muscle strength and function

Quadriceps stregnth. Strength will be measured using a portable purposely built non-extendable strain gauge (load cell). The participant will exert maximal force against the strap assembly for 3 s.
Timepoint [2] 302453 0
Cross sectional design - assessment at one point only: prior knee replacement surgery
Secondary outcome [3] 302454 0
Pain and function.
The physical function, pain and stiffness will be assessed using, Western Ontario and McMaster University Osteoarthritis Index (WOMAC), a self administered questionnaire.
Timepoint [3] 302454 0
Cross sectional design- assessment will be done at one point time only prior knee replacement surgery

Eligibility
Key inclusion criteria
People with severe knee osteoarthritis who scheduled for knee replacement surgery
Minimum age
50 Years
Maximum age
90 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
people with Rhematoid Arthritis

Study design
Purpose
Screening
Duration
Cross-sectional
Selection
Case control
Timing
Prospective
Statistical methods / analysis
Individual variables will be compared between groups with a one-way or two-way analysis of variance (ANOVA) with appropriate post hoc multiple comparison. Pearson’s correlation coefficient will be used to investigate the relationship between pain, function and gait and muscle waste factors.

Power calculation -
Power and Precision software have been used to calculate the estimated sample size based on our preliminary work *. We have reported a significantly higher level of the inflammatory marker JNK1 in the knee osteoarthritis group compared to the aged-matched control group. Using JNK1 in our power calculation, 20 participants in each group is sufficient for a power of 80% and alpha=0.05.
*Levinger I, et al. Increased inflammatory cytokine expression in the vastus lateralis of patients with knee osteoarthritis. Arthritis and Rheumatism 2011;63:1343-48.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
7/02/2012
Actual
22/02/2012
Date of last participant enrolment
Anticipated
1/10/2012
Actual
31/10/2012
Date of last data collection
Anticipated
Actual
Sample size
Target
40
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 939 0
Warringal Private Hospital - Heidelberg

Funding & Sponsors
Funding source category [1] 287159 0
Government body
Name [1] 287159 0
Arthritis Australia
Country [1] 287159 0
Australia
Primary sponsor type
University
Name
Victoria University
Address
VICTORIA UNIVERSITY
PO Box 14428
MELBOURNE VIC 8001
Country
Australia
Secondary sponsor category [1] 285927 0
University
Name [1] 285927 0
La Trobe University
Address [1] 285927 0
La Trobe University
Melbourne Victoria 3086
Australia
Country [1] 285927 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 289154 0
La Trobe University ethics committee
Ethics committee address [1] 289154 0
Ethics committee country [1] 289154 0
Australia
Date submitted for ethics approval [1] 289154 0
Approval date [1] 289154 0
01/04/2011
Ethics approval number [1] 289154 0
FHEC08/150
Ethics committee name [2] 289155 0
Victoria University ethics committee
Ethics committee address [2] 289155 0
Ethics committee country [2] 289155 0
Australia
Date submitted for ethics approval [2] 289155 0
Approval date [2] 289155 0
08/04/2011
Ethics approval number [2] 289155 0
HRETH 08/149
Ethics committee name [3] 289156 0
Warringal Hospital
Ethics committee address [3] 289156 0
Ethics committee country [3] 289156 0
Australia
Date submitted for ethics approval [3] 289156 0
Approval date [3] 289156 0
30/03/2011
Ethics approval number [3] 289156 0

Summary
Brief summary
People with knee osteoarthritis (OA) often have leg muscle weakness and difficulty moving and walking. Impaired muscular performance is a major determinant of daily function and disability. However, it is not known if loss of muscle mass and strength in knee OA occurs as an indirect result of reduced limb use, or if muscle itself is a direct target of the degenerative processes active in OA. Given that personal mobility is an essential factor for healthy independent living of those who suffer from this chronic degenerative condition, research into the preservation of muscle mass is essential for developing successful therapy to restore and maintain effective limb use.
In this study we aim to determine the effect of muscle inflammation on muscle function and impaired walking pattern relative to OA joint degeneration.
Trial website
NA
Trial related presentations / publications
Levinger I, Levinger P, Trenerry M, Feller JA, Bartlett JR, Bergman NR, McKenna. M, Cameron-Smith. D Increased inflammatory cytokine expression in the vastus lateralis of patients with knee osteoarthritis. Arthritis and Rheumatism, 63(5), 1343-1348, 2011

Levinger P, Levinger I, Trenerry M, Feller JA, Bartlett JR, Bergman NR, McKenna. M, Cameron-Smith. D. The association between skeletal muscle inflammatory markers and walking pattern in people with knee osteoarthritis –Arthritis Care and Research, 63(12), 1715-1721, 2011
Public notes

Contacts
Principal investigator
Name 39502 0
Dr Pazit Levinger
Address 39502 0
Institute of Sport, Exercise & Active Living (ISEAL)
VICTORIA UNIVERSITY
PO Box 14428
MELBOURNE VIC 8001
Country 39502 0
Australia
Phone 39502 0
61-3-99195525
Fax 39502 0
Email 39502 0
[email protected]
Contact person for public queries
Name 39503 0
Pazit Levinger
Address 39503 0
Institute of Sport, Exercise & Active Living (ISEAL)
VICTORIA UNIVERSITY
PO Box 14428
MELBOURNE VIC 8001
Country 39503 0
Australia
Phone 39503 0
61-3-99195525
Fax 39503 0
Email 39503 0
[email protected]
Contact person for scientific queries
Name 39504 0
Pazit Levinger
Address 39504 0
Institute of Sport, Exercise & Active Living (ISEAL)
VICTORIA UNIVERSITY
PO Box 14428
MELBOURNE VIC 8001
Country 39504 0
Australia
Phone 39504 0
61-3-99195525
Fax 39504 0
Email 39504 0
[email protected]

No information has been provided regarding IPD availability


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
SourceTitleYear of PublicationDOI
EmbaseThe level of FoxO1 and IL-15 in skeletal muscle, serum and synovial fluid in people with knee osteoarthritis: a case control study.2016https://dx.doi.org/10.1007/s00198-015-3473-7
N.B. These documents automatically identified may not have been verified by the study sponsor.