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Trial registered on ANZCTR


Registration number
ACTRN12610000739011
Ethics application status
Approved
Date submitted
1/09/2010
Date registered
6/09/2010
Date last updated
19/09/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
Folate and methotrexate (MTX) in rheumatoid arthritis (RA)
Scientific title
Folate supplementation in rheumatoid arthritis (RA) patients receiving methotrexate – are we impairing the efficacy of methotrexate (MTX)?
Secondary ID [1] 252608 0
N/A
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Rheumatoid arthritis 257895 0
Condition category
Condition code
Inflammatory and Immune System 258056 258056 0 0
Rheumatoid arthritis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
All patients in this trial will be taking methotrexate (MTX). The dose will vary between patients depending on their disease activity and the decision of their prescribing physician.

The exact mechanism of action of methotrexate remains unclear but it acts as a folate antagonist. Therefore all patients receiving methotrexate receive 5mg/week of oral folic acid in an effort to reduce occurrence of methotrexate associated adverse effects. Patients will continue taking folate for as long as they remain on methotrexate (MTX). This may be long term if it is providing adequate control of their rheumatoid arthritis (RA).

The intervention is a reduced dose (0.8mg/weekly) of oral folate as a supplement to methotrexate.
Intervention code [1] 256946 0
Treatment: Drugs
Comparator / control treatment
The control treatment is 5mg/weekly of oral folate. Patients will continue taking folate for as long as they remain on methotrexate (MTX). This may be long term if it is providing adequate control of their rheumatoid arthritis (RA).
Control group
Dose comparison

Outcomes
Primary outcome [1] 258917 0
Change in DAS28 (disease activity scale) at 6 months.

Disease activity will be assessed using standard clinical parameters comprising: swollen joint count, tender joint count, physicians global score (visual analogue scale)modified Health Assessment Questionnaire (mHAQ) patient pain and fatigue visual analogue scales, and standardised questions related to side effects related to methotrexate.

Side effects may include dizziness; headaches; loss of appetite; mild hair loss; nausea; stomach pain or upset; tiredness; vomiting.
Timepoint [1] 258917 0
Weeks 0, 4, 8, 12 and 24
Primary outcome [2] 259126 0
Occurrence of MTX associated adverse effects.

The occurrence of methotrexate adverse events will be sought at each visit. A standardised questionnaire will be used to assess for presence/absence and severity of adverse events.
Timepoint [2] 259126 0
Weeks 0, 4, 8, 12 and 24
Secondary outcome [1] 265443 0
The relationship between the change in red blood cell (RBC) folate and change in RA disease activity.

Disease activity will be assessed using standard clinical parameters comprising: swollen joint count, tender joint count, physicians global score (visual analogue scale)modified Health Assessment Questionnaire (mHAQ) patient pain and fatigue visual analogue scales, and standardised questions related to side effects related to methotrexate.
Timepoint [1] 265443 0
Weeks 0, 4, 8, 12 and 24
Secondary outcome [2] 265445 0
The relationship between change in red blood cell (RBC) folate and change in RBC methotrexate (MTX) polyglutamate concentrations.
Timepoint [2] 265445 0
Weeks 0, 4, 8, 12 and 24

Eligibility
Key inclusion criteria
Inclusion criteria:
1. Male or female, aged >18 yrs, with RA as defined by the American Rheumatology Association Criteria

2. Methotrexate either as monotherapy or combination therapy for at least three months with a stable oral dose of MTX between 5 to 25mg weekly over the preceding four weeks

3. Inadequate response to MTX as defined by DAS28>3.2

4. Able and willing to give written informed consent and to comply with the requirements of the study.
Minimum age
18 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. A change in dose or introduction of another disease modifying anti-rheumatic drug, non-steroidal anti-inflammatory agent or oral steroid within the preceding month.

2. Intra-articular steroid injection within one month prior to enrolment

3. Evidence of serious uncontrolled chronic concomitant disease.

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)
64 patients receiving MTX for the treatment of RA will be recruited. All patients will be from the Christchurch Hospital Rheumatology service.

Patients with DAS28>3.2 will have either intramuscular steroid injection (Kenacort 80mg) or no steroid depending on the patient and rheumatologist decision. Patients will then be randomised on a 1:1 baseline to either continue folic acid 5mg/week or to reduce folic acid to 0.8mg/week. 'Allocation is not conceal

Patient randomisation will be stratified according to the baseline DAS28 in to two strata =3.2-4.5 and >4.5
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Patients will be randomised on a 1:1 baseline to either continue folic acid 5mg/week or to reduce folic acid to 0.8mg/week. Patient randomisation will be stratified according to the baseline DAS28 in to two strata >3.2 - 4.5 and >4.5 - 6.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/12/2010
Actual
1/02/2011
Date of last participant enrolment
Anticipated
Actual
16/08/2013
Date of last data collection
Anticipated
Actual
Sample size
Target
64
Accrual to date
Final
40
Recruitment outside Australia
Country [1] 2806 0
New Zealand
State/province [1] 2806 0
Canterbury

Funding & Sponsors
Funding source category [1] 257566 0
Charities/Societies/Foundations
Name [1] 257566 0
Arthritis New Zealand
Country [1] 257566 0
New Zealand
Primary sponsor type
Individual
Name
Associate Professor Lisa Stamp
Address
Department of Medicine
Christchurch School of Medicine
P.O Box 4345
Christchurch
Country
New Zealand
Secondary sponsor category [1] 256791 0
Individual
Name [1] 256791 0
Dr Peter Chapman
Address [1] 256791 0
Department of Rheumatology/Immunology/Allergy
Christchurch Hospital
Private Bag 4710
Christchurch
Country [1] 256791 0
New Zealand
Secondary sponsor category [2] 256793 0
Individual
Name [2] 256793 0
Dr John O'Donnell
Address [2] 256793 0
Department of Rheumatology/Immunology/Allergy
Christchurch Hospital
Private Bag 4710
Christchurch
Country [2] 256793 0
New Zealand
Other collaborator category [1] 251471 0
Individual
Name [1] 251471 0
Associate Professor Chris Frampton
Address [1] 251471 0
Christchurch School of Medicine
P.O Box 4345
Christchurch
Country [1] 251471 0
New Zealand
Other collaborator category [2] 251472 0
Individual
Name [2] 251472 0
Associate Professor Murray Barclay
Address [2] 251472 0
Christchurch School of Medicine
P.O Box 4345
Christchurch
Country [2] 251472 0
New Zealand

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 259422 0
Upper South A Regional Ethics Committee
Ethics committee address [1] 259422 0
Ethics committee country [1] 259422 0
New Zealand
Date submitted for ethics approval [1] 259422 0
06/09/2010
Approval date [1] 259422 0
30/09/2010
Ethics approval number [1] 259422 0
URA/10/9/70

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 31479 0
Prof Lisa Stamp
Address 31479 0
Department of Medicine
P.O.Box 4345
Christchurch 8014
Country 31479 0
New Zealand
Phone 31479 0
+3640953
Fax 31479 0
Email 31479 0
lisa.stamp@cdhb.govt.nz
Contact person for public queries
Name 14726 0
Associate Professor Lisa Stamp
Address 14726 0
Department of Medicine
Christchurch School of Medicine
P.O Box 4345
Christchurch 8140
Country 14726 0
New Zealand
Phone 14726 0
+64 3 3640953
Fax 14726 0
+64 3 3640935
Email 14726 0
lisa.stamp@cdhb.govt.nz
Contact person for scientific queries
Name 5654 0
Associate Professor Lisa Stamp
Address 5654 0
Department of Medicine
Christchurch School of Medicine
P.O Box 4345
Christchurch 8140
Country 5654 0
New Zealand
Phone 5654 0
+64 3 3640953
Fax 5654 0
+64 3 3640935
Email 5654 0
lisa.stamp@cdhb.govt.nz

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

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