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 measure
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 (if study stopped)
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
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
Basic results (scientific)
Publication list
1. 2013 results in http://www.ncbi.nlm.nih.gov/pubmed/23300331
Publication citations
-
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.