Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12615000124538
Ethics application status
Approved
Date submitted
20/01/2015
Date registered
11/02/2015
Date last updated
25/11/2019
Date data sharing statement initially provided
19/12/2018
Date results information initially provided
19/12/2018
Type of registration
Retrospectively registered

Titles & IDs
Public title
Investigation and prevention of Rheumatoid Arthritis before symptom onset
Scientific title
Prospective observational cohort of unaffected first-degree relatives (FDR) of probands with Rheumatoid Arthritis (RA) and healthy controls followed for five years with the simultaneous collection of tissue samples; designed to examine the role of genetic and environmental factors influencing the development and progression of RA-related autoimmunity and to identify and explore immunological alterations prior to the onset of disease, to establish the proportion of FDRs who develop RA defined by the ACR 2010 classification criteria at 5 years and to identify biomarkers in FDRs prior to and at onset of disease for disease prediction, diagnosis and prognosis of RA and to direct and guide treatment.
Secondary ID [1] 286006 0
Nil
Universal Trial Number (UTN)
U1111-1166-3140
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Rheumatoid Arthritis 293968 0
Condition category
Condition code
Musculoskeletal 294268 294268 0 0
Other muscular and skeletal disorders
Inflammatory and Immune System 294381 294381 0 0
Rheumatoid arthritis

Intervention/exposure
Study type
Observational
Patient registry
True
Target follow-up duration
5
Target follow-up type
Years
Description of intervention(s) / exposure
Observational Study - To follow prospectively a cohort of unaffected first-degree relatives (FDR) of people with rheumatoid arthritis (RA) annually for five years. FDR will be evaluated and data obtained including demographic information, medical history, environmental exposures questionnaire, connective tissue disease screening questionnaire, physical examination, joint counts and tissue samples collected including blood, mouth and faecal swabs.
Intervention code [1] 290986 0
Not applicable
Comparator / control treatment
Observation control - healthy control group and RA proband group will be seen once and not followed prospectively.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 294065 0
The proportion of FDRs who develop RA defined by the ACR 2010 classification criteria at 5 years.


Timepoint [1] 294065 0
5 years
Secondary outcome [1] 312438 0
The identification of genetic factors contributing to the development of RA. DNA will be collected and all patients genotyped.
Timepoint [1] 312438 0
Baseline, 1, 2, 3, 4 and 5 years after commencement of observation
Secondary outcome [2] 312677 0
The identification of microbial factors contributing to the development of RA. Mouth and faecal swabs will be collected and using next-generation sequencing techniques including shotgun metagenomic sequencing, 16S rRNA metagenomic sequencing and microbial metatranscriptomics we will analyse the microbial communities.
Timepoint [2] 312677 0
Baseline, 1, 2, 3, 4 and 5 years after commencement of observation
Secondary outcome [3] 312678 0
The identification of environmental factors contributing to the development of RA. Environmental questionnaires specifically designed for this study will be completed at all time points.
Timepoint [3] 312678 0
Baseline, 1, 2, 3, 4 and 5 years after commencement of observation
Secondary outcome [4] 312679 0
The identification of immunological factors contributing to the development of RA. Serum and peripheral blood mononuclear cells will be separated from collected whole blood and using various techniques including flow cytometry, cell sorting techniques, ELISA and qPCR; we will identify, enumerate and phenotype immune cells contributing to RA development.
Timepoint [4] 312679 0
Baseline, 1, 2, 3, 4 and 5 years after commencement of observation
Secondary outcome [5] 312680 0
To identify predictive risk biomarkers prior to the onset of disease. All genetic, microbial, environmental and immunological data will be analysed for potential biomarkers of disease development.
Timepoint [5] 312680 0
Baseline, 1, 2, 3, 4 and 5 years after commencement of observation

Eligibility
Key inclusion criteria
Participant is willing and able to give informed consent for participation in the study.

Male or Female, aged 18 years or above.
Be a first-degree relative (parent, full-sibling or offspring) of a person with RA (FDR), have been diagnosed with RA (of any disease duration and severity (Proband), or a healthy volunteer without a family history of RA and are in good health (Healthy Control).

Able (in the Investigators opinion) and willing to comply with all study requirements.

Willing to allow his or her General Practitioner and consultant, if appropriate, to be notified of participation in the study.
Minimum age
18 Years
Maximum age
85 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Any significant disease or disorder which, in the opinion of the Investigator, may either put the participants at risk because of participation in the study, or may influence the result of the study, or the participant’s ability to participate in the study.

Participants who have participated in another research study involving an investigational product in the past 12 weeks

Study design
Purpose
Natural history
Duration
Longitudinal
Selection
Defined population
Timing
Prospective
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Date of first participant enrolment
Anticipated
20/01/2015
Actual
20/01/2015
Date of last participant enrolment
Anticipated
Actual
13/12/2016
Date of last data collection
Anticipated
14/12/2021
Actual
Sample size
Target
700
Accrual to date
Final
268
Recruitment in Australia
Recruitment state(s)
QLD

Funding & Sponsors
Funding source category [1] 290598 0
Government body
Name [1] 290598 0
National Health and Medical Research Council
Country [1] 290598 0
Australia
Primary sponsor type
University
Name
University of Queensland Diamantina Institute
Address
University of Queensland Diamantina Institute,
Translational Research Institute
Level 6 37 Kent Street
Woolloongabba QLD 4102
Country
Australia
Secondary sponsor category [1] 289285 0
Charities/Societies/Foundations
Name [1] 289285 0
Gallipoli Medical Research Foundation
Address [1] 289285 0
Greenslopes Private Hospital
Newdegate Street, Greenslopes QLD 4120.
Country [1] 289285 0
Australia
Secondary sponsor category [2] 289286 0
Hospital
Name [2] 289286 0
Princess Alexandra Hospital
Address [2] 289286 0
Ipswich Road
Woolloongabba QLD 4102
Country [2] 289286 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 292232 0
Greenslopes Research and Ethics Committee
Ethics committee address [1] 292232 0
Greenslopes Private Hospital
Newdegate Street
Greenslopes QLD 4120
Ethics committee country [1] 292232 0
Australia
Date submitted for ethics approval [1] 292232 0
Approval date [1] 292232 0
14/10/2014
Ethics approval number [1] 292232 0
14/53
Ethics committee name [2] 292233 0
University of Queensland Medical Research Ethics Committee
Ethics committee address [2] 292233 0
UQ Research and Innovation
Cumbrae-Stewart Building (#72)
BRISBANE QLD 4072
Ethics committee country [2] 292233 0
Australia
Date submitted for ethics approval [2] 292233 0
Approval date [2] 292233 0
03/11/2014
Ethics approval number [2] 292233 0
2014001457

Summary
Brief summary
This trial will establish a large multi-centre prospective cohort and tissue bio-bank of unaffected first-degree relatives (FDR) of probands with RA designed to examine the role of genetic, environmental and microbial factors influencing the development and progression of RA-related autoimmunity. FDRs will be followed annually with an expected 15% likely to develop asymptomatic autoimmunity and to progress to RA within 5 years. This population cohort with accompanying genetic, environmental and immunological data will characterise more precisely people at risk of RA, allowing detection and risk stratification prior to symptoms becoming apparent.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 54226 0
Dr Helen Benham
Address 54226 0
The University of Queensland Diamantina Institute
Translational Research Institute
Level 6, 37 Kent St, Woolloongabba QLD 4102
Australia
Country 54226 0
Australia
Phone 54226 0
+61 07 3443 6947
Fax 54226 0
+61 07 3443 6966
Email 54226 0
[email protected]
Contact person for public queries
Name 54227 0
Dr Helen Benham
Address 54227 0
The University of Queensland Diamantina Institute
Translational Research Institute
Level 6, 37 Kent St, Woolloongabba QLD 4102
Australia
Country 54227 0
Australia
Phone 54227 0
+61 07 3443 6947
Fax 54227 0
+61 07 3443 6966
Email 54227 0
[email protected]
Contact person for scientific queries
Name 54228 0
Dr Helen Benham
Address 54228 0
The University of Queensland Diamantina Institute
Translational Research Institute
Level 6, 37 Kent St, Woolloongabba QLD 4102
Australia
Country 54228 0
Australia
Phone 54228 0
+61 07 3443 6947
Fax 54228 0
+61 07 3443 6966
Email 54228 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
Not in the ethics


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
TypeIs Peer Reviewed?DOICitations or Other DetailsAttachment
Conference abstractNo Benham, Helen, Wood, John, Nagl, Lisa, Maradana, M... [More Details]

Documents added automatically
No additional documents have been identified.