ANZCTR - Registration

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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 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]

Nil

Universal Trial Number (UTN)

U1111-1143-1559

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

rheumatoid arthritis

Condition category

Condition code

Inflammatory and Immune System

Rheumatoid arthritis

Alternative and Complementary Medicine

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]

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]

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]

12 months

Secondary outcome [1]

time to achieving remission according to ACR criteria (joint scores, patient reported outcomes, inflammatory markers)

Timepoint [1]

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?

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)

Recruitment hospital [1]

The Royal Adelaide Hospital - Adelaide

Recruitment hospital [2]

The Queen Elizabeth Hospital - Woodville

Recruitment postcode(s) [1]

5000 - Adelaide

Funding & Sponsors

Funding source category [1]

Government body

Name [1]

NHMRC

Address [1]

National Health and Medical Research Council
GPO Box 1421
Canberra ACT 2601

Country [1]

Australia

Primary sponsor type

Hospital

Name

Royal Adelaide Hospital

Address

North Terrace, adelaide, SA 5000

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Royal Adelaide Hospital

Ethics committee address [1]

North Terrace Adelaide SA 5000

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

Approval date [1]

19/11/1998

Ethics approval number [1]

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

A/Prof Susanna Proudman

Address

Rheumatology Unit
Royal Adelaide Hospital
North Terrace
Adelaide SA 5000

Country

Australia

Phone

+618 82225190

Fax

+618 82225895

sproudman@internode.on.net

Contact person for public queries

Name

Susanna Proudman

Address

Rheumatology Unit
Royal Adelaide Hospital
North Terrace
Adelaide SA 5000

Country

Australia

Phone

+618 82225190

Fax

+618 82225895

sproudman@internode.on.net

Contact person for scientific queries

Name

Susanna Proudman

Address

Rheumatology Unit
Royal Adelaide Hospital
North Terrace
Adelaide SA 5000

Country

Australia

Phone

+618 82225190

Fax

+618 82225895

sproudman@internode.on.net

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

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

No documents have been uploaded by study researchers.

Documents added automatically

Source	Title	Year of Publication	DOI
Dimensions AI	Fish oil in recent onset rheumatoid arthritis: a randomised, double-blind controlled trial within algorithm-based drug use	2013	https://doi.org/10.1136/annrheumdis-2013-204145
Embase	Plasma n-3 fatty acids and clinical outcomes in recent-onset rheumatoid arthritis.	2015	https://dx.doi.org/10.1017/S0007114515002718

N.B. These documents automatically identified may not have been verified by the study sponsor.

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