Condition category
Musculoskeletal Diseases
Date applied
08/12/2010
Date assigned
09/05/2011
Last edited
24/06/2013
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Prof Philip Conaghan

ORCID ID

Contact details

Section of Musculoskeletal Disease
Chapel Allerton Hospital
Chapeltown Road
Leeds
LS7 4SA
United Kingdom

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

RR08/8797

Study information

Scientific title

An open label study to assess the effectiveness of oral methotrexate at reducing pain in knee osteoarthritis

Acronym

PROM

Study hypothesis

Osteoarthritis (OA) is the most common arthritis worldwide and causes significant pain and disability. Current treatments including non-steroidal anti-inflammatory drugs (NSAIDs) and opioids have significant side-effects. There is an urgent need for safe, long-term treatments for pain in OA.

Recent imaging studies, in particular magnetic resonance imaging (MRI) have demonstrated that synovitis is very common in OA of the knee and strongly associated with pain. Methotrexate (MTX) is a safe and effective treatment for synovitis with good efficacy and long-term safety in inflammatory arthritides. This 24 week open label study evaluates the effectiveness of methotrexate at pain reduction in knee OA. We also assessed ultrasound-detected synovitis.

Ethics approval

Leeds (West) Research Ethics Committee approved on the 26th March 2009 (ref: 09/H1307/11)

Study design

Single centre open label study

Primary study design

Interventional

Secondary study design

Non randomised controlled trial

Trial setting

Other

Trial type

Treatment

Patient information sheet

Not available in web format, please contact c.y.j.wenham@leeds.ac.uk to request a patient information sheet

Condition

Osteoarthritis of the knee

Intervention

Oral methotrexate up to 20 mg for 24 weeks. No placebo (open label).

Intervention type

Drug

Phase

Phase IV

Drug names

Methotrexate

Primary outcome measures

Change in VAS (0 - 100 mm) pain scores at 24 weeks. VAS pain scores will be measured at baseline and 24 weeks, to assess knee pain within the last 48 hours.

Secondary outcome measures

1. Changes on ultrasound scan at baseline and 24 weeks. Ultrasound images will be scored for synovitis and effusion, measured in milimetres.
2. Change in Osteoarthritis Quality of Life Questionnaire (OAQoL) score, measured at baseline, 12 and 24 weeks
3. Change in Hospital Anxiety and Depression Scale (HADS) score, measured at baseline, 12 and 24 weeks
4. Change in Western Ontario and McMasters University Index (WOMAC) pain, function and stiffness subscales , measured at baseline, 12 and 24 weeks
5. Change in West Haven-Yale Multidimensional Pain Inventory scores, measured at baseline, 12 and 24 weeks
6. Change in VAS pain scores measured at baseline and 12 weeks

Overall trial start date

31/07/2009

Overall trial end date

31/03/2011

Reason abandoned

Eligibility

Participant inclusion criteria

1. Knee pain on most days in the last 3 months
2. Insufficient pain relief from, or inability to tolerate NSAIDs and/or opioids
3. Patient able to identify a predominantly painful knee (the signal knee)
4. Moderate to severe pain of the signal knee as defined by a score of greater than or equal to 40 mm on a Visual Analogue Scale (VAS) (0 - 100 mm) using the question "On average, how would you rate your knee pain during the last 3 months?"
5. Fulfil clinical American College of Rheumatology (ACR) criteria for knee OA
6. A previous radiograph (X-Ray) of the signal knee with changes consistent with osteoarthritis
7. Men and women must use adequate birth control measures (e.g. abstinence, oral contraceptives, intra-uterine device, barrier method with spermicide, or surgical sterilisation) for the duration of the study and should continue such precautions for 6 months after receiving the last dose of methotrexate. If female and have potential for child bearing then a negative pregnancy test must be performed prior to starting treatment.
8. The patient must be able to adhere to the study visit schedule and other protocol requirements
9. The patient must be capable of giving informed consent and the consent must be obtained prior to any screening procedures
10. All patients with pre-existing lung disease/smokers must have had a chest radiograph (X-Ray) within the last 6 months
11. Aged 53 - 85 years, either sex

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

30 fully recruited

Participant exclusion criteria

1. The presence of any rheumatic diseases that could be responsible for secondary osteoarthritis
2. Use of intra-articular hyaluronic acid in the signal knee or the use of depo corticosteroid injection within the 6 months preceding enrolment in the study
3. Use of intra-articular corticosteroid injections in the 3 months preceding enrolment
4. The use of oral or parenteral steroids in the 2 months preceding the study
5. Knee injury or diagnostic arthroscopy within the 6 months preceding enrolment in the study
6. A history of knee surgery in the signal knee at any time
7. The presence of non-OA causes of pain in the signal knee, e.g. referred hip pain, osteonecrosis
8. Women who are pregnant, nursing, or men or women planning pregnancy within 12 months after screening (i.e. approximately 6 months following last study medications)
9. Use of any investigational (unlicensed) drug within 1 month prior to screening or within 5 half-lives of the investigational agent, whichever is longer
10. Significant haematological or biochemical abnormality:
10.1. Haemoglobin less than or equal to 8.5 g/dL
10.2. White cell count (WCC) less than or equal to 3.5 x 109/L
10.3. Neutrophils less than or equal to 1.5 x 109/L
10.4. Platelets less than or equal to 100 x 109/L
10.5. Alanine aminotransferase (ALT) greater than two times the upper limit of normal (ULN) for the laboratory conducting the test
10.6. Creatinine greater than 1.5 times ULN for the laboratory conducting the test
11. Have current signs or symptoms of severe, progressive or uncontrolled renal, hepatic, haematological, gastrointestinal, endocrine, pulmonary, cardiac, neurologic, or cerebral disease
12. Intake of alcohol above the recommended government guidelines (2 units per day for women, 3 units per day for men)
13. Poor tolerability of venepuncture or lack of adequate venous access for required blood sampling during the study period

Recruitment start date

31/07/2009

Recruitment end date

31/03/2011

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Section of Musculoskeletal Disease
Leeds
LS7 4SA
United Kingdom

Sponsor information

Organisation

University of Leeds (UK)

Sponsor details

QA department
Research and Development
34
Hyde Terrace
Leeds
LS2 9LN
United Kingdom

Sponsor type

University/education

Website

http://www.leeds.ac.uk/

Funders

Funder type

University/education

Funder name

University of Leeds (UK)

Alternative name(s)

Funding Body Type

private sector organisation

Funding Body Subtype

academic

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

1. 2013 results in http://www.ncbi.nlm.nih.gov/pubmed/23300331

Publication citations

  1. Results

    Wenham CY, Grainger AJ, Hensor EM, Caperon AR, Ash ZR, Conaghan PG, Methotrexate for pain relief in knee osteoarthritis: an open-label study., Rheumatology (Oxford), 2013, 52, 5, 888-892, doi: 10.1093/rheumatology/kes386.

Additional files

Editorial Notes