Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12613000579796
Ethics application status
Approved
Date submitted
16/05/2013
Date registered
23/05/2013
Date last updated
23/07/2019
Date data sharing statement initially provided
23/07/2019
Date results information initially provided
23/07/2019
Type of registration
Retrospectively registered

Titles & IDs
Public title
Fish oil in recent onset rheumatoid arthritis: High versus low dose fish oil on a background of dose-responsive combination disease-modifying anti-rheumatic drugs.
Scientific title
Fish oil in anti-inflammatory doses in recent onset rheumatoid arthritis: A randomized, double-blind controlled trial within algorithm-based drug use with DMARD use as the primary outcome.
Secondary ID [1] 282516 0
Nil
Universal Trial Number (UTN)
U1111-1143-1559
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
rheumatoid arthritis 289177 0
Condition category
Condition code
Inflammatory and Immune System 289498 289498 0 0
Rheumatoid arthritis
Alternative and Complementary Medicine 289512 289512 0 0
Other alternative and complementary medicine

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
High dose fish oil group receive 10mL / day liquid fish oil concentrate (BLT Incromega TG3525) providing 5.5g/d EPA+DHA. Incromega TG3525 has 35% EPA and 25% DHA. Taken orally. Duration of therapy 3 years.
Plasma phospholipids used to monitor adherence to therapy
Intervention code [1] 287173 0
Treatment: Other
Comparator / control treatment
Low dose group (control group) receivd 10 mL / day liquid sunola oil : capelin oil (2:1) providing 400mg/d EPA+DHA. Sunola oil is a monounsaturated oil, capelin fish oil has 6.6%EPA and 5.7% DHA a low dose of which is added to the sunola oil for the purposes of masking smell and taste but with little addition of EPA+DHA. Taken orally. Duration of therapy 3 years.
Plasma phospholipids used to monitor adherence to therapy
Control group
Dose comparison

Outcomes
Primary outcome [1] 289602 0
The design of this RCT has allowed the effects of fish oil to be assessed in the context of modern disease-modifying anti-rheumatic drugs (DMARD) treatment for RA. A structured treatment algorithm responsive to disease activity and tolerance, allows drug use to be used as an outcome measure for the effects of fish oil. Specifically, doses of combination DMARDs (methotrexate, sulphasalazine, hydroxychloroquine) are increased until the target disease activity is reached (a treat-to-target strategy). The primary endpoint is time to failure of this triple therapy, requiring addition of another DMARD leflunomide.
Timepoint [1] 289602 0
12 months
Secondary outcome [1] 302826 0
time to achieving remission according to ACR criteria (joint scores, patient reported outcomes, inflammatory markers)
Timepoint [1] 302826 0
12 months

Eligibility
Key inclusion criteria
Inclusion criteria: subjects must be 18 years or older, have rheumatoid arthritis (RA) according to the 1987 revised ACR criteria with polyarthritis of less than 12 months’ duration, at least 3 swollen joints and ESR greater than 28 mm/hour and/or CRP greater than 10 mg/dL and be DMARD-naive.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria: use of DMARDs other than antimalarials, use of antimalarials for more than 1 month, recent seroconversion to parvovirus, Ross River, Barmah Forest or rubella viruses, antinuclear antibody titre greater than 1:320, hepatitis B, hepatitis C or human immunodeficiency virus, known sensitivity to methotrexate, sulphasalazine or hydroxychloroquine, or systemic disease likely to increase the risk of toxicity to 1 or more of these drugs.

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)
Consecutive patients attending the early arthritis clinic are considered for inclusion. If they enrol, allocation is concealed from the trail co-ordinators with allocation being by the provision of numbered containers of oil.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
in standard permuted block approach in block sizes of 6
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
3/09/2001
Actual
3/09/2001
Date of last participant enrolment
Anticipated
8/12/2008
Actual
8/12/2008
Date of last data collection
Anticipated
Actual
17/02/2009
Sample size
Target
140
Accrual to date
Final
140
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 1017 0
The Royal Adelaide Hospital - Adelaide
Recruitment hospital [2] 1018 0
The Queen Elizabeth Hospital - Woodville
Recruitment postcode(s) [1] 6892 0
5000 - Adelaide

Funding & Sponsors
Funding source category [1] 287298 0
Government body
Name [1] 287298 0
NHMRC
Country [1] 287298 0
Australia
Primary sponsor type
Hospital
Name
Royal Adelaide Hospital
Address
North Terrace, adelaide, SA 5000
Country
Australia
Secondary sponsor category [1] 286050 0
None
Name [1] 286050 0
Address [1] 286050 0
Country [1] 286050 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 289273 0
Royal Adelaide Hospital
Ethics committee address [1] 289273 0
North Terrace Adelaide SA 5000
Ethics committee country [1] 289273 0
Australia
Date submitted for ethics approval [1] 289273 0
Approval date [1] 289273 0
19/11/1998
Ethics approval number [1] 289273 0
RAH Protocol No. 981105

Summary
Brief summary
The omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) can suppress synthesis of the omega-6 pro-inflammatory eicosanoids, prostaglandin E2 and leukotriene B4. Meta-analysis of 10 randomised controlled trials (RCTs) in 1995 reported that fish oil supplementation reduced tender joint count and duration of morning stiffness. Meta-analysis in 2007 of 17 RCTs of fish oil in inflammatory joint pain included 14 RA studies and reported a benefit of fish oil for patient assessed pain, morning stiffness, number of painful and/or tender joints and NSAID consumption. Collectively, these studies determined that symptomatic benefits were seen above doses of 2.7g EPA+DHA per day after a delay of 2 to 3 months.

There were at least two features common to these RCTs that are problematic for demonstrating the potential for use of fish oil in RA. Firstly, participants had established disease with the average disease duration being 10.2 +/- 5.2 years across all studies. Secondly, DMARD use was not ‘real life’. DMARDs were held constant with the need for change being a withdrawal criterion, or if drug variation was allowed, it was not according to pre-defined rules.
This is an investigator-initiated, double-blind RCT with fish oil in recent onset RA with disease duration < 12 months, using a study design which addresses some of the shortcomings of previous RCTs of fish oil in RA. A treatment algorithm for DMARD use that is responsive to disease activity and tolerability / toxicity, according to pre-defined rules, allows the extent of DMARD to be used as an outcome measure.
Trial website
none
Trial related presentations / publications
Susanna M Proudman, Michael J James, Llewellyn D Spargo, Robert G Metcalf, Thomas R Sullivan, Maureen Rischmueller, Katerina Flabouris, Mihir D Wechalekar, Anita T Lee, Leslie G Cleland. Fish oil in recent onset rheumatoid arthritis: a randomised, double-blind controlled trial within algorithm-based drug use. Ann Rheum Dis 2015;74:89–95.
Public notes

Contacts
Principal investigator
Name 40118 0
A/Prof Susanna Proudman
Address 40118 0
Rheumatology Unit
Royal Adelaide Hospital
North Terrace
Adelaide SA 5000
Country 40118 0
Australia
Phone 40118 0
+618 82225190
Fax 40118 0
+618 82225895
Email 40118 0
[email protected]
Contact person for public queries
Name 40119 0
A/Prof Susanna Proudman
Address 40119 0
Rheumatology Unit
Royal Adelaide Hospital
North Terrace
Adelaide SA 5000
Country 40119 0
Australia
Phone 40119 0
+618 82225190
Fax 40119 0
+618 82225895
Email 40119 0
[email protected]
Contact person for scientific queries
Name 40120 0
A/Prof Susanna Proudman
Address 40120 0
Rheumatology Unit
Royal Adelaide Hospital
North Terrace
Adelaide SA 5000
Country 40120 0
Australia
Phone 40120 0
+618 82225190
Fax 40120 0
+618 82225895
Email 40120 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
Relevant staff have moved on and we don't have the resources to retrieve individual data.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually

Documents added automatically
SourceTitleYear of PublicationDOI
EmbasePlasma n-3 fatty acids and clinical outcomes in recent-onset rheumatoid arthritis.2015https://dx.doi.org/10.1017/S0007114515002718
Dimensions AIFish oil in recent onset rheumatoid arthritis: a randomised, double-blind controlled trial within algorithm-based drug use2013https://doi.org/10.1136/annrheumdis-2013-204145
N.B. These documents automatically identified may not have been verified by the study sponsor.