Knee osteoarthritis MedDRA version: 18.0 Level: PT Classification code 10031161 Term: Osteoarthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders MedDRA version: 18.0 Level: LLT Classification code 10023476 Term: Knee osteoarthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders MedDRA version: 18.0 Level: LLT Classification code 10031166 Term: Osteoarthritis knees System Organ Class: 10028395 - Musculoskeletal and connective t
Conditions
Interventions
Trade Name: Methotrexate
Product Name: Methotrexate
Pharmaceutical Form: Tablet
INN or Proposed INN: methotrexate sodium
CAS Number: 59-05-2
Concentration unit: mg milligram(s)
Concentration type: eq
Sponsors
University of Leeds
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients to be included must meet the following criteria: 1. Fulfil clinical ACR Criteria for knee OA. 2. Knee pain on most days in the last 3 months. 3. Insufficient pain relief from, inability to tolerate, or contra-indication to oral and/or topical NSAIDs and/or opioids. Moderate to severe pain of the signal knee as defined by a score of =40mm on a VAS (0-100mm) using the question “On average, how would you rate your knee pain during the last 3 months?”. 4. Knee pain is the predominant pain condition. 5. Patient able to identify a ‘signal’ painful knee (either the most painful knee or selected from equally painful knees). 6. A radiograph (X-Ray) of the signal knee within the last 2 years with changes consistent with tibiofemoral OA. 7. No change in the average weekly dose of oral/topical analgesics (including NSAIDs) for at least 4 weeks. 8. Has used chondroitin or glucosamine for at least 3 months with no change to the average weekly dose, is not using or is willing to stop using if recently started. 9. All male and female subjects biologically capable of having children must agree to use a reliable method of contraception for the duration of the study and 24 weeks after the end of the study period. Acceptable methods of contraception are surgical sterilisation, oral, implantable or injectable hormonal methods, intrauterine devices or barrier contraceptives.If female and have potential for child bearing then a negative pregnancy test must be performed prior to starting treatment. 10. The patient must be able to adhere to the study visit schedule and other protocol requirements. 11. The patient must be capable of giving informed consent and the consent must be obtained prior to any screening procedures. 12. All patients must have had a chest radiograph (X-Ray) within the last 6 months. 13. Aged >/= 18 years Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 60 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 100
Exclusion criteria
Exclusion criteria: Patients will be excluded from this study for any of the following reasons: 1. The presence of any inflammatory arthritis (e.g. gout, reactive arthritis, rheumatoid arthritis, psoriatic arthritis, seronegative spondylarthropathy, previous diagnosis of pseudogout in target joint with proven crystals on joint aspiration or elevated CRP at time of knee arthritis flare) or fibromyalgia. 2. Use of intra-articular (IA) hyaluronic acid in the signal knee within the 4 months preceding enrolment in the study. 3. Use of IA, IM or oral corticosteroids in the 3 months preceding enrolment. 4. Use of other anti-synovial agents (e.g. hydroxychloroquine or sulphasalazine) in the 2 months preceding the study. 5. Significant knee injury or any knee surgery within the 6 months preceding enrolment in the study. 6. A history of partial or complete joint replacement surgery in the signal knee at any time, listed for knee surgery or anticipating knee surgery during the study period. 7. Commencement of physiotherapy or non-pharmacological knee OA treatment in the 2 months preceding the study. 8. The presence of non-OA causes of pain in the signal knee e.g. referred hip pain, osteonecrosis. 9. Women who are pregnant, breast-feeding, or men or women planning pregnancy within 18 months after screening (i.e. approximately 6 months following last study medications). 10. Use of any investigational (unlicensed) drug within 1 month prior to screening or within 5 half-lives of the investigational agent, whichever is longer. 11. Have current signs or symptoms of severe, progressive or uncontrolled renal, hepatic, haematological, gastrointestinal, endocrine, pulmonary, cardiac, neurologic, cerebral disease, or active current infection. 12. Uncontrolled disease states, such as moderate/severe asthma, COPD or inflammatory bowel disease, where flares are commonly treated with oral or parenteral corticosteroids, or recurrent infections. 13. Unwilling to keep alcohol intake to below the recommended maximum daily limit during the trial (2 units per day for women, 3 units per day for men). 14. Planned need for live vaccination during 12 months of study (e.g. for foreign travel) with exception of Zostavax® which is permissible. 15. Poor tolerability of venepuncture or lack of adequate venous access for required blood sampling during the study period. 16. Melanoma, squamous cell carcinoma or non-skin cancer in the past 3 years. 17. Intolerance to lactose. 18. Significant haematological or biochemical abnormality a. Haemoglobin =2 times ULN for the laboratory conducting the test. f. Creatinine > 1.5 times ULN for the laboratory conducting the test g. eGFR <30ml/minute Subjects with the following contra-indications to MRI scanning will not be included in the MRI substudy but may still be enrolled into the main study: • Pacemakers • Surgical clips within the head • Certain inner ear implants • Neuro-electrical stimulators • Metal fragments within the eye or head
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to determine whether methotrexate is an effective treatment for relieving pain in knee OA.;Secondary Objective: The secondary objective is to determine whether methotrexate is a cost effective treatment for knee OA.;Primary end point(s): The primary outcome will be change in knee pain between baseline and 6 months (24 weeks). This will be measured using an 11 point numerical rating scale (NRS) with the anchor questions ‘On average, how would you rate your overall knee pain severity over the last week (7 days)', at 6 months (24 weeks) after the start of treatment.;Timepoint(s) of evaluation of this end point: 6 months (24 weeks) n.b. “Month” will be the label used on all follow-up CRF’s, and is defined as a period of 4 weeks for the purposes of the PROMOTE Trial. | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: 0, 3, 6, 9, 12 months as stated above. n.b. “Month” will be the label used on all follow-up CRF’s, and is defined as a period of 4 weeks for the purposes of the PROMOTE Trial.;Secondary end point(s): Clinical endpoints (at 0, 3, 6, 9, 12 months) • Patient reported knee pain • Disease activity and knee function • Pain in other joints; Quality of life endpoints (at 0, 6, 12 months) • Quality of life • Anxiety and depression Resource use endpoints (at 0, 6, 9, 12 months) • Health service resource utilisation Imaging/MRI endpoints (MRI substudy at 0 and 6 months) • Synovitis and cartilage scores | — |
Countries
United Kingdom
Contacts
Public ContactSarah Hogg
University of Leeds
Outcome results
None listed