Erosive Osteoarthritis, Hand Osteoarthritis
Conditions
Brief summary
A placebo-controlled randomized controlled trial exploring the effect of methotrexate on pain, function and structural outcomes in erosive inflammatory hand osteoarthritis.
Detailed description
The trial will include Norwegian adult males and females with symptomatic erosive inflammatory hand osteoarthritis. Participants will be randomized 1:1 to either: 1. Methotrexate oral x 1/week; weekly starting dose 15 mg for two weeks, followed by 20 mg the remaining weeks (intervention group). Dosage can be reduced to as low as 10 mg if higher doses are not tolerated. 2. Placebo (control group). Both arms will receive folic acid 1mg daily. The treatment duration for both groups is 52 weeks.
Interventions
Sponsors
Oslo University Hospital
Diakonhjemmet Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Identical placebo cannot be produced due to text, color and shape of methotrexate tablets. Thus, both placebo and methotrexate will be encapsulated to ensure blinding.
Intervention model description
An investigator-initiated, randomized, double-blinded, placebo-controlled, parallel-group, single-center, phase IV, superiority study, exploring the effect of methotrexate on pain, function and structural outcomes in erosive inflammatory hand osteoarthritis.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Finger joint pain 40-80 on 0-100 visual analog scale (VAS) with insufficient pain relief from, inability to tolerate or contra-indications to oral paracetamol and/or NSAIDs, and hand symptoms (pain, aching, or stiffness) on most days the previous 6 weeks before randomization. * Hand OA according to the American College of Rheumatology (ACR) criteria, at least 1 distal (DIP) or proximal interphalangeal (PIP) joint of the 2nd-5th finger with radiographic pre-erosive (J-phase) or erosive disease (E-phase) according to the Verbruggen-Veys anatomical phase system, and at least two DIP/PIP joints with power Doppler signal of at least grade 1 or grey-scale synovitis of at least grade 2 on ultrasound.
Exclusion criteria
A full list of the
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Finger pain on a visual analogue scale | 6 months | Difference in self-reported finger joint pain previous 48 hours on a 0-100 mm scale at 6 months of treatment; higher value indicate worse outcome. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| AUSCAN | Month 1, 3, 6, 9 and 12. | Australian/Canadian hand index (AUSCAN), sum score 0-60, higher value indicate worse outcome. |
| Concomitant medication | Month 1, 3, 6, 9 and 12. | Concomitant medication |
| Tender and swollen joints | Month 1, 3, 6, 9 and 12. | Number of tender and swollen joints (range 0-30), higher values indicate more affected joints. |
| Physician-reported disease activity on a visual analogue scale | Month 1, 3, 6, 9 and 12. | Patient-reported disease activity on a 0-100 mm scale; higher value indicate worse outcome. |
| Hand radiographs: Kellgren Lawrence | Month 6 and 12 | Conventional radiographs: change in radiographic severity according to Kellgren-Lawrence scale, range 0-4 in each joint higher value indicate worse outcome. |
| Hand radiographs: Verbruggen-Veys anatomical phase scoring system | Month 6 and 12 | Conventional radiographs: radiographic severity in finger joints according to Verbruggen-Veys anatomical phase scoring system, range 1-5; higher value indicate worse outcome. |
| Hand radiographs: OARSI atlas | Month 6 and 12 | Conventional radiographs: rdiographic severity according to the Osteoarthritis Research Society International (OARSI) atlas for the presence/severity of osteophytes, joint space narrowing and erosions. |
| Hand MRI | Month 6 | MRI of dominant hand: number of joints with synovitis and BMLs |
| Hand ultrasound | Month 1, 3, 6, 9 and 12. | Ultrasound: number of finger joints with synovial thickening and power Doppler signals. |
| Knee ultrasound | Month 6 | Ultrasound: degree of synovitis in knee joints |
| Hip ultrasound | Month 6 | Ultrasound: degree of synovitis in hip joints |
| Adverse events | Through study completion, maximum 12 months, in addition to 3 months after end of treatment. | Number of adverse events, serious adverse events, and withdrawals because of adverse events. |
| Finger pain on a visual analogue scale | Month 1, 3, 9 and 12. | Self-reported finger pain previous 48 hours on a 0-100 mm scale; higher value indicate worse outcome. |
| Thumb pain on a visual analogue scale | Month 1, 3, 6, 9 and 12. | Self-reported thumb pain previous 48 hours on a 0-100 mm scale; higher value indicate worse outcome. |
| Pain most painful finger joint on a visual analogue scale | Month 1, 3, 6, 9 and 12. | Pain most painful finger joint last 48 hours on a 0-100 mm scale; higher value indicate worse outcome. |
| Patient-reported disease activity on a visual analogue scale | Month 1, 3, 6, 9 and 12. | Patient-reported disease activity last 48 hours on a 0-100 mm scale; higher value indicate worse outcome. |
| Pain all joints on a visual analogue scale | Month 1, 3, 6, 9 and 12. | Pain all joints last 48 hours on a 0-100 mm scale; higher value indicate worse outcome. |
| Hand diagram pain | Month 6. | Finger pain and thumb base pain (yes/no) on hand diagram |
| Body diagram pain | Month 6. | Pain in other joints (yes/no) on body diagram |
| OMERACT-OARSI responder criteria | Month 1, 3, 6, 9 and 12. | Fulfillment of Outcome Measures in Rheumatology Osteoarthritis Research Society International (OMERACT-OARSI) responder criteria. |
| EQ-5D | Month 1, 3, 6, 9 and 12. | Quality-adjusted life years (QALYs) based on the health-related utility scores measured by the generic instrument EuroQol 5 dimensions (EQ-5D), sum score 5-35, higher value indicate worse outcome, in addition to a 0-100 visual analogue scale where higher value indicate better outcome. |
| MHOQ | Month 6. | Michigan Hand Outcomes Questionnaire (MHOQ) pain and physical function subscales; function subscale range 10-50, higher value indicate worse outcome; task subscale range 17-85, higher value indicate worse outcome; work subscale range 5-25, higher value indicate worse outcome; pain subscale range 10-48, higher value indicate better outcome. |
| Grip strength | Month 1, 3, 6, 9 and 12. | Grip strength (in kg; using a hand dynamometer) |
| HOOS-12 | Month 6. | Hip disability and Osteoarthritis Outcome Score (HOOS)-12, range 12-60, higher value indicate worse outcome. |
| KOOS-12 | Month 6. | Knee injury and Osteoarthritis Outcome Score (KOOS)-12, range 12-60, higher value indicate worse outcome. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Question about blinding | Month 12 | The participants are asked which treatment they think they have received |
| HADS | Month 6 | Hospital Anxiety and Depression Scales (HADS), range 0-42, higher value indicate worse outcome. |
| PCS | Month 6 | Pain catastrophizing scale, range 0-12, higher value indicate worse outcome. |
| PSQ | Month 6 | Pain Sensitivity Questionnaire (PSQ), range 0-170, higher value indicate worse outcome. |
| Anchor questions for MCII and PASS | Month 6 | Questions about perceived improvement and acceptable symptom state that will be used to define minimally clinically important improvement and patient acceptable symptom state for other questionnaires |
| ASES | Month 6 | Arthritis Self Efficacy Scale (ASES), range 10-100, higher value indicate better outcome. |
| Pain sensitization | Month 6 | Pain sensitization: Pressure Pain Thresholds (PPT) by digital algometer; temporal summation by punctate probes; Conditioned Pain Modulation (CPM) by blood pressure ischemic test. |
| Soluble biomarkers of extracellular matrix turnover | Month 6 and 12 | Markers of collagen degradation (s-COMP, s-C1M, s-C2M, s-C3M, s-CTX1, sHA), collagen synthesis (s-proC2), aggrecan degradation (s-huARGS) and inflammation (s-calprotectin, s- vimentin, s-hsCRP and s-CRPM); Inflammatory cytokines (IL-1β, IL-1ra, IL-4, IL-6, IL-10, IL-12, IL-17, IL-18, IL-21, IFN-γ, TNF-α, VEGF, GM-CSF, CCL2, CCL3, CCL4, CXCL10) and hormones (leptin and resistin). |
| Omics | Month 6 and 12 | Omics analyses of whole blood |
| Sub-study: knee pain on a visual analogue scale | Month 6 | Self-reported knee pain previous 48 hours on a 0-100 mm scale at 6 months of treatment; higher value indicate worse outcome. |
| Sub-study: biopsy of knee OA | Month 6 | Change in synovial cellular composition and gene expression with single-cell RNA sequencing analyses; subgroup analyses, n=16 patients |
Countries
Norway
Outcome results
None listed