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Trial registered on ANZCTR


Registration number
ACTRN12611000048987
Ethics application status
Not yet submitted
Date submitted
4/01/2011
Date registered
13/01/2011
Date last updated
13/01/2011
Type of registration
Prospectively registered

Titles & IDs
Public title
A study of proteins involved in the inflammation and pain associated with arthritis of the knee.
Scientific title
The relationship between clinical phenotype and kinin bioregulation in arthritis
Secondary ID [1] 253344 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Rhuematoid arthritis 258877 0
Gout 258878 0
Osteoarthritis 258879 0
Psoriatic arthritis 258880 0
Condition category
Condition code
Musculoskeletal 259020 259020 0 0
Other muscular and skeletal disorders

Intervention/exposure
Study type
Observational
Patient registry
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
Aspiration of synovial fluid, by insertion of a needle into the inflammed joint and removal of fluid.
Collection of serum through phlebotomy
Collelction of urine
All samples are collected at the same time.
The observational study is cross sectional, with each subject having one visit at one point in time.
Intervention code [1] 257791 0
Not applicable
Comparator / control treatment
Nil
Control group
Uncontrolled

Outcomes
Primary outcome [1] 259872 0
To compare kallikrein-kinin cascade mRNA and protein expression in neutrophils harvested from blood and SF of patients with arthritis (RA, PsA, gout, OA).
Immunocytochemistry: Expression of the kallikrein-kinin cascade proteins in will be assessed using labelling techniques. Immunolabelling will be performed on blood and SF neutrophils using fully characterised specific antibodies. Visualization of the images will be by immunofluorescence, confocal, and phase-contrast microscopy, with quantitation by image analysis.
Flow cytometry: Neutrophils will be harvested from blood and SF and analysed on a FACScan instrument using specific fluorescently labelled antibodies.
mRNA expression: Total RNA will be extracted from blood and SF neutrophils (RNeasy Kit, Qiagen) and reverse transcribed to cDNA. mRNA for KLK1, KLKB1, KNG1, BDKRB1 and BDKRB2 will be detected by real time PCR using highly specific TaqMan primer/probes (Applied Biosystems). Steady-state mRNA levels will be normalized to the levels of 18S rRNA and differences in gene expression will be evaluated by the Ct method. Results will be analyzed for statistical significance using t tests or one-way ANOVA.
Timepoint [1] 259872 0
end of trial
Primary outcome [2] 259873 0
To assess whether activation of kinin B1 or B2 receptors by their respective endogenous agonists increases the expression and release of MMP-2 and -9 from neutrophils harvested from blood and SF of patients with arthritis (RA, PsA, gout, OA).
Quantitative real-time PCR analysis of metalloproteases 2 and 9 will be performed using TaqMan? Gene Expression primer/probes (Applied Biosystems).
Kinin levels in plasma and SF will be determined by ELISA.
Neutrophils will be pre-treated ex vivo with cytochalasin B (20 g/ml for 10 min) and then stimulated with bradykinin or Lys-des-Arg9-bradykinin (1, 10 and 100 nM). Degranulation of neutrophils and release of matrix metalloprotease-9 and myeloperoxidase into the medium will be measured using ELISAs.
Timepoint [2] 259873 0
End of trial
Primary outcome [3] 259940 0
To compare the kinin bioregaultion assessed above with clinical symptoms, including pain as collected by VAS, function as asessed by HAQ, and Quality of Life as assesed by SF 36
Timepoint [3] 259940 0
end of trial
Secondary outcome [1] 268749 0
To examine the primary outcomes 1,2 and 3 to the phenotype of arthritis, including diagnosis, symptoms and biomarkers of inflammation (ultrasound synovitis, hsCRP and metabolic syndrome)
Timepoint [1] 268749 0
end of trial

Eligibility
Key inclusion criteria
OA of the knee based on ACR clinical criteria
Active gout of the knee
RA meeting ACR criteria
PsA meeting CASPAR criteria
Minimum age
No limit
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Contraindication or unwillingness to undergo an US scan
Contraindication or unwillingness to undergo arthrocentesis
(Including an INR> 2)
Diagnosis of septic arthritis, Paget’s disease, articular fracture, ochronosis, acromegaly, haemochromatosis, Wilson’s disease, primary osteochondrosis
Injury to the study knee within 6 months of the study start
knee joint replacement (partial or total); osteotomy of the studied joint; with arthroscopy of the studied joint made within 1 year of the study start
With an intra articular injection of steroids made within 4 weeks and/or intra articular injection of radionuclide made with 3 months prior to study entry

Study design
Purpose
Natural history
Duration
Cross-sectional
Selection
Defined population
Timing
Prospective
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/02/2011
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
95
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 258261 0
Charities/Societies/Foundations
Name [1] 258261 0
Raine Medical Research Foundation
Country [1] 258261 0
Australia
Primary sponsor type
Hospital
Name
Royal Perth Hospital
Address
Murray Street,
Perth,
WA
6000
Country
Australia
Secondary sponsor category [1] 257429 0
None
Name [1] 257429 0
Address [1] 257429 0
Country [1] 257429 0
Other collaborator category [1] 251754 0
University
Name [1] 251754 0
Lung Institute of Western Australia (LIWA)
Address [1] 251754 0
Lung Institute of Western Australia
Ground Floor E Block
Sir Charles Gairdner Hospital
Hospital Avenue
Nedlands Western Australia 6006
Country [1] 251754 0
Australia

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 260238 0
Royal Perth Hospital Ethics Committee
Ethics committee address [1] 260238 0
Royal Perth Hospital,
Murray Street Perth,
WA
6000.
Ethics committee country [1] 260238 0
Australia
Date submitted for ethics approval [1] 260238 0
13/01/2011
Approval date [1] 260238 0
Ethics approval number [1] 260238 0

Summary
Brief summary
A study of proteins involved in the inflammation and pain associated with arthritis of the knee
The study involves inviting people with a diagnosis of arthritis of the knee to participate in the study. The treatment for their arthritis will not be altered in any way. Participants will be asked to attend a single appointment, which will take about 2 hours and the following will occur:
Questions about their health and specifically their arthritis and about any medications they are taking. This will be followed by a physical examination by the doctor (including weight, height, abdominal and waist circumference, BP)
Questionnaires about pain, and difficulties/disability caused by the arthritis and associated pain.
The knee joint will be examined by a doctor and undergo an ultrasound examination of the knee.
The fluid in the knee will be withdrawn through a needle.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 32049 0
Address 32049 0
Country 32049 0
Phone 32049 0
Fax 32049 0
Email 32049 0
Contact person for public queries
Name 15296 0
Helen Keen
Address 15296 0
Level 4, MRF buidling
Rear 50 Murray Street.
Perth, WA
6000
Country 15296 0
Australia
Phone 15296 0
+61 8 9224 0244
Fax 15296 0
+61 8 9224 0246
Email 15296 0
helen.keen@uwa.edu.au
Contact person for scientific queries
Name 6224 0
Helen Keen
Address 6224 0
Level 4, MRF buidling
Rear 50 Murray Street.
Perth, WA
6000
Country 6224 0
Australia
Phone 6224 0
+61 8 9224 0244
Fax 6224 0
+61 8 9224 0246
Email 6224 0
helen.keen@uwa.edu.au

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
No additional documents have been identified.