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Trial registered on ANZCTR


Registration number
ACTRN12617000170325
Ethics application status
Approved
Date submitted
27/12/2016
Date registered
1/02/2017
Date last updated
8/01/2019
Date data sharing statement initially provided
8/01/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
T-BIRD: Tissue Biomechanics and Inflammation in the Rheumatic Diseases
Scientific title
T-BIRD: Tissue Biomechanics and Inflammation in the Rheumatic Diseases

The Relationship Between Articular, Cutaneous and Vascular Biomechanical Properties, The Risk of Developing and the Severity of the Arthritis and Cardiovascular Disease Occurring in Rheumatoid and Psoriatic Arthritis – A Preliminary Study
Secondary ID [1] 290809 0
None
Universal Trial Number (UTN)
Trial acronym
T-BIRD
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Rheumatoid Arthritis 301461 0
Psoriatic Arthritis 301462 0
Benign Joint Hypermobility 301463 0
Cardiovascular Disease 301464 0
Condition category
Condition code
Musculoskeletal 301182 301182 0 0
Other muscular and skeletal disorders
Cardiovascular 301183 301183 0 0
Diseases of the vasculature and circulation including the lymphatic system
Inflammatory and Immune System 301238 301238 0 0
Rheumatoid arthritis

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
Assessments of the elasticity / stiffness of the joints, skin and arteries.
1. Participants will answer a simple 5-point questionnaire asking questions about the mobility of their joints.
2. An assessor will painlessly assess the range of motion of the joints of the finger joints, wrists, elbows, knees and spine.
3. The flexibility of the right 5th finger will be formally tested in a device that stretches the finger backwards using specific forces (torques).
4. The skin elasticity will be evaluated first by drawing two dots 10 mm apart on th dorm of the right hand and measuring how far they can be stretched apart by the examiner.
5. The skin elasticity of the solar aspect of the right forearm will be measured as the volume of skin/tissue that can be drawn into the barrel of a 50mL syringe (plunger removed) in response to specific negative pressures.
6. The thickness of the skin will be measured at both sites using a pair of Harpenden skin fold callipers.
7. Arterial stiffest will be firstly measured as carotid-femoral pulse wave velocity (the delay between the the carotid and femoral pulses measured using a pressure transducer applied to the carotid and an inflatable cuff around the thigh. Carotid-Femoral Pulse Wave Velocity will be repeated on a second occasion 1 day - 4 weeks of the first assessment. Then endothelial fiction, the ability to dilate, will be measured as the strength of the pulses in the finger tips after a 5 minute period of complete occlusion of blood flow to the left arm using an inflatable cuff.

Assessment of the severity of arthritis (in the rheumatoid arthritis and psoriatic arthritis groups)
1. Severity of arthritis will be evaluated as the number of tender and swollen joints, blood tests for inflammation (ESR, CRP) (to determine how well arthritis is controlled) and
2. The strength of treatment required to achieve this control (what drugs the participant is receiving).

These assessments will be conducted over two visits. The majority of the assessments can be completed on the first visit. Upon the second visit carotid-femora pulse wave velocity will be measured a second time and any assessments not already conducted on the first occasion will be completed on the second occasion.

Intervention code [1] 296732 0
Not applicable
Comparator / control treatment
Two Control Groups will be evaluated using all the same assessments as those conducted upon the Case Groups (outlined in 'Description of intervention' field.)
1. Healthy Controls
2. Benign joint hypermobiity
Control group
Active

Outcomes
Primary outcome [1] 300599 0
A specially designed device constructed from Meccano will be used to measure angular displacement of 5th finger metacarpophalangeal joint in response to torque applied to extend the finger. The right hand is strapped into the device positioned such that the 5th finger MCP can be extended by rotation of a lever arm attached to a pulley through which forces can be applied to generate a range of torques to extend the finger.
Timepoint [1] 300599 0
Baseline (cross-sectional study)
Primary outcome [2] 300600 0
Endothelial Function (Peripheral Arterial Tonometry) - EndoPAT Device
Timepoint [2] 300600 0
Baseline (Cross-sectional Study)
Primary outcome [3] 300601 0
Skin Elasticity (Syringe Test) - Volume Displacement in Response to Negative Pressure (suction force) applied to dominant forearm.
Timepoint [3] 300601 0
Baseline (cross-sectional study)
Secondary outcome [1] 330390 0
Clinical Skin Extensibility Scores (CSES)
Timepoint [1] 330390 0
Baseline (cross-sectional study)
Secondary outcome [2] 330391 0
Aortic stiffness (Carotid-Femoral Pulse Wave Velocity)
Timepoint [2] 330391 0
Baseline (cross-sectional study)
Secondary outcome [3] 330392 0
Beighton Score for Articular Hypermobility
Timepoint [3] 330392 0
Baseline (cross-sectional study)
Secondary outcome [4] 330393 0
Beighton Questionnaire for Articular Hypermobility
Timepoint [4] 330393 0
Baseline (cross-sectional study)
Secondary outcome [5] 330394 0
Radiographic Damage (Sharpe Scores) in Rheumatoid and Psoriatic Arthritis Groups
Timepoint [5] 330394 0
Baseline (cross-sectional study)
Secondary outcome [6] 330395 0
Severity of Arthritis based upon Treatment Requirements and Disease Activity (Rheumatoid and Psoriatic Arthritis Groups)
Timepoint [6] 330395 0
Baseline (cross-sectional study)
Secondary outcome [7] 330396 0
PASI (Psoriasis Area and Severity Index) Score in Psoriasis and Psoriatic Arthritis Groups
Timepoint [7] 330396 0
Baseline (cross-sectional study)
Secondary outcome [8] 331155 0
The Syringe Test for skin elasticity will be further evaluated in a sub-study entitled the Syringe Test Sub-Study.

In this study the Syringe test will be performed in 10 participants at two time points before and 3 months after commencing treatment with corticosteroids to determine whether corticosteroids influence the assessment. Study participants will include patients receiving high dose corticosteroids for any indication that does not affect the skin.
Timepoint [8] 331155 0
Prior to commencement of corticosteriod treatment and 3 months post commencement of corticosteroid treatment.
Secondary outcome [9] 331156 0
Skin fold thickness dorm right hand and solar aspect right forearm.
Timepoint [9] 331156 0
Baseline

Eligibility
Key inclusion criteria
Main Study
Case Groups
1. ACPA-positive Rheumatoid Arthritis (RA);
2. People at risk of developing ACPA-positive RA;
a. First Degree Relatives of people with ACPA-Positive RA;
b. People with a positive ACPA blood test who do not have RA;
3. Psoriatic Arthritis (PsA)
4. Cutaneous Psoriasis without psoriatic arthritis
Control Groups
1. Healthy Controls Unrelated to people with RA ;
2. Benign Joint Hypermobility (BJH)

Syringe Test Sub-Study
1. Any medical condition requiring corticosteroid therapy that does not affect the skin (e.g. giant cell arteritis, asthma, interstitial lung disease or systemic vasculitis).
Minimum age
18 Years
Maximum age
80 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Main Study

Syringe Test Sub-Study
Conditions affecting the skin such as psoriasis, Systemic Lupus Erythematosus, scleroderma or high alcohol intake;

Case or Control groups for the study – RA, PsA, psoriasis, Joint Hypermobility;
Prior corticosteroid exposure.

Study design
Purpose
Natural history
Duration
Cross-sectional
Selection
Case control
Timing
Both
Statistical methods / analysis
Correlation of assessments of articular, arterial and cutaneous stiffness. Methods to be determined by data (normal / skewed / dichotomous)

Comparison of assessments of articular, arterial and cutaneous stiffness between study groups. Methods to be determined by data (normal / skewed / dichotomous)

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 7178 0
John Hunter Hospital - New Lambton
Recruitment postcode(s) [1] 14939 0
2305 - New Lambton

Funding & Sponsors
Funding source category [1] 295234 0
Hospital
Name [1] 295234 0
John Hunter Hospital
Address [1] 295234 0
Rheumatology Department
John Hunter Hospital
Lookout Rd
New Lambton
NSW 2305
Country [1] 295234 0
Australia
Primary sponsor type
Individual
Name
Dr Stephen Oakley
Address
Rheumatology Department
John Hunter Hospital
Lookout Rd
New Lambton
NSW 2305
Country
Australia
Secondary sponsor category [1] 294062 0
None
Name [1] 294062 0
Address [1] 294062 0
Country [1] 294062 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 296576 0
Hunter New England Research Ethics Committee
Ethics committee address [1] 296576 0
Dr Nicole Gerrand
Executive Officer
Hunter New England Human Research Ethics Committee
Locked Bag No. 1
New Lambton NSW 2305
Ethics committee country [1] 296576 0
Australia
Date submitted for ethics approval [1] 296576 0
14/12/2016
Approval date [1] 296576 0
08/02/2017
Ethics approval number [1] 296576 0

Summary
Brief summary
The currently accepted paradigm holds that systemic autoimmunity and inflammation have a directly causal relationship with rheumatoid arthritis (RA) and psoriatic arthritis (PsA) and with the associated cardiovascular (CV) disease. However, the evidence supporting this paradigm is inconclusive and possibly contradicted but clinical studies.

The T-BIRD study inverts the existing paradigm to explore the hypothesis that while autoimmunity sets the stage for the development of arthritis, it is the connective tissue biomechanical properties (stiffness) that:
1. Determine the risk of developing RA and PsA
2. Influence the severity of the RA and PsA and;
3. Determine the severity of the CV disease seen in association with RA and PsA .

If this hypothesis is confirmed then a considerable part of the inheritance of RA and PsA (much of which remains unaccounted for) might be explained. There would also be important clinical implications as it would change the way clinicians undertake risk assessment and therapeutic decisions in managing inflammatory arthritis and its associated cardiovascular disease.

This preliminary study will begin exploring this hypothesis by evaluating the relationship between articular biomechanical characteristics in the joints, skin and arteries and exploring the relationships between tissue biomechanical properties upon rheumatoid and psoriatic arthritis and vascular and cutaneous disease.
Trial website
Trial related presentations / publications
Public notes
Attachments [1] 1345 1345 0 0

Contacts
Principal investigator
Name 71350 0
A/Prof Stephen Oakley
Address 71350 0
Department of Rheumatology
John Hunter Hospital
Lookout Rd
New Lambton
NSW 2305
Country 71350 0
Australia
Phone 71350 0
+61 249 223 500
Fax 71350 0
+61 249 223 562
Email 71350 0
stephen.oakley@hnehealth.nsw.gov.au
Contact person for public queries
Name 71351 0
A/Prof Stephen Oakley
Address 71351 0
Department of Rheumatology
John Hunter Hospital
Lookout Rd
New Lambton
NSW 2305
Country 71351 0
Australia
Phone 71351 0
+61 249 223 500
Fax 71351 0
+61 249 223 562
Email 71351 0
stephen.oakley@hnehealth.nsw.gov.au
Contact person for scientific queries
Name 71352 0
A/Prof Stephen Oakley
Address 71352 0
Department of Rheumatology
John Hunter Hospital
Lookout Rd
New Lambton
NSW 2305
Country 71352 0
Australia
Phone 71352 0
+61 249 223 500
Fax 71352 0
+61 249 223 562
Email 71352 0
stephen.oakley@hnehealth.nsw.gov.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No/undecided IPD sharing reason/comment
What supporting documents are/will be available?
Summary results
No Results