Hand Osteoarthritis
Conditions
Brief summary
To compare metformin (2 g daily), or maximum tolerated dose, for 16 weeks with placebo as a treatment of hand osteoarthritis symptoms.
Interventions
DRUGMetformin
Metformin will be initiated at 500 mg once daily with breakfast meal. The dose will be increased with 500 mg every week until 2 g/day is reached, distributed as 1000 mg every morning and evening, together with a meal. If the subject cannot tolerate the maximum dose (2 g/day), the maximal tolerated dose will be given. The treatment period including titration is 16 weeks.
DRUGPlacebo
Participants in the placebo group will receive a placebo tablet identical to the metformin tablet
Sponsors
Marius Henriksen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age ≥18 years 2. Hand OA according to the ACR criteria 3. Average finger (2 to 5) pain ≥4 on a 0-10 numeric rating scale (NRS where 10 is worst pain) over the past 30 days 4. Metformin naive
Exclusion criteria
Comorbidities 1. History of, or current signs of medical disease that may affect joints, e.g. rheumatoid arthritis, gout, psoriatic arthritis 2. Psoriasis 3. Known malignancy (except successfully treated squamous or basal cell skin carcinoma) 4. Drug or alcohol abuse in the last year 5. Existing nerve entrapment syndromes (e.g. carpal tunnel syndrome) 6. Known diabetes 7. Generalised pain syndromes such as fibromyalgia 8. Known peripheral neuropathies 9. Known allergies towards the interventions 10. Gastric bypass or other malabsorption syndrome 11. In case of pharmacological weight loss medication (e.g. glucagon like peptide-1 (GLP-1) analogues) or pharmacological osteoporosis medication, dosage must have been stable for 3 months without any plan of up-titration during the study period 12. Any other condition or impairment that, in the opinion of the investigator, makes a potential participant unsuitable for participation or obstructs participation e.g. psychiatric disorders. Surgical history 13. History of hand surgery in the target hand within 12 months prior to enrolment 14. History of arthroplasty, arthrodesis or surgical treatment of thumb base osteoarthritis in the target hand Management strategies 15. Use of systemic corticosteroids equivalent of ≥ 7.5 mg prednisolone daily within 3 months 16. Treatment with denosumab (Prolia/Xgeva) 17. Participation in experimental device or experimental drug study 3 months prior to enrolment 18. Intra-articular treatments of any kind of any joint of the target hand 3 months before inclusion 19. Current use of synthetic or non-synthetic opioids 20. Planning to start other treatment for hand OA in the study participation period 21. Planned CT scan with iodine contrast 22. Scheduled surgery on upper extremity of the target hand during study participation 23. Scheduled surgery requiring pause of metformin, e.g. surgery in general anaesthesia, during study participation Reproductive system 24. Pregnancy 25. Planned pregnancy within the study period, 3 months after end of study treatment for female fertile participant and 6 months after end of study treatment for male participant 26. Insufficient anti-conception therapy for female fertile participants within the study period and 3 months after end of study treatment * Sufficient anti-conception therapy consists of intra-uterine device (coil), hormonal anti-conception (birth control pills, implant, intra-uterine system, dermal patch, vaginal ring, or injections) or sexual abstinence * Female participants are considered infertile if they are postmenopausal or if they have undergone surgical sterilisation (bilateral salpingectomy, hysterectomy or bilateral oophorectomy) * Postmenopausal state is defined as no menses for 12 months without alternative medical cause before inclusion in the study 27. Insufficient anti-conception therapy for male participants within the study period and 6 months after end of study treatment * Sufficient anti-conception therapy consists of condom or sexual abstinence * Male participants are considered sterile if they have undergone surgical sterilisation (vasectomy) 28. Breast-feeding Blood analysis 29. Positive anti-cyclic citrullinated peptide (\>10 kU/L) 30. eGFR \<60 ml/min/1.73 m2 31. Vitamin B12 deficiency \< 200 pmol/L 32. Hba1c ≥ 48 mmol/mol
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Finger pain | Week 16 | Change from baseline in Visual Analogue Scale (VAS) finger joint pain of the target hand after 16 weeks of treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Thumb base pain | Week 16 | Change from baseline after 16 weeks of treatment in Visual Analogue Scale thumb base pain of the target hand |
| Hand pain | Week 16 | Change from baseline after 16 weeks of treatment in pain of both hands assessed by Australian/Canadian Osteoarthritis Hand Index hand pain subscale |
| Physician tender joint count | Week 16 | Change from baseline after 16 weeks of treatment in joint activity of the target hand assessed by physician tender joint count |
| Function | Week 16 | Change from baseline after 16 weeks of treatment in physical function assessed by Australian/Canadian Osteoarthritis Hand Index (AUSCAN) physical function subscale |
| Quality of life assessed by the European Quality of life - 5 dimensions (EQ-5D) scale | Week 16 | Change from baseline after 16 weeks of treatment in quality of life assessed by the European Quality of life - 5 dimensions scale |
| Hand strength | Week 16 | Change from baseline after 16 weeks of treatment in hand strength of the target hand assessed by a grip dynamometer |
| Number of treatment responders | Week 16 | Responders will be identified according to OMERACT-OARSI criteria, defined as (1) improvement in finger pain (primary outcome) or function (secondary outcome) ≥50% and an absolute change ≥20 mm; or (2) improvement of ≥20% with an absolute change ≥10 mm in at least two of the following three: finger pain (primary outcome), function (secondary outcome), and patient global assessment (secondary outcome). |
| Patient global assessment | Week 16 | Change from baseline after 16 weeks of treatment in Visual Analogue Scale patient global assessment |
Other
| Measure | Time frame | Description |
|---|---|---|
| Inflammatory biomarker | Week 16 | Change in hsCRP mg/L |
| Metabolic outcomes | Week 16 | Change in HbA1c mmol/mol |
| Swollen joint count | Week 16 | Change in physician swollen joint count of the target hand |
| Proteomics | Week 16 | Change in mass-spectrometry based proteomics |
| Vitamin K | Week 16 | Change in vitamin K and dephospho-uncarboxylated matrix Gla-protein ((dp)ucMGP) pmol/L |
| Stiffness of both hands | Week 16 | Change in stiffness of both hands measured on the Australian/Canadian Osteoarthritis Hand Index (AUSCAN) stiffness subscale |
| Composite of pain, function and stiffness | Week 16 | Change in pain, function and stiffness of both hands measured composite on the Australian/Canadian Osteoarthritis Hand Index (AUSCAN) Hand Index Score |
| Physical function | Week 16 | Change in physical function of both hands assessed by the Health Assessment Questionnaire Disability Index (HAQ-DI) |
| Physician global assessment | Week 16 | Change in physician global assessment of disease activity of hand OA in the target hand measured on a Visual Analogue Scale (VAS) scale |
| Fatigue | Week 16 | Change in fatigue measured on a Visual Analogue Scale (VAS) scale |
| Sleep quality | Week 16 | Change in sleep quality measured on the Pittsburgh Sleep Quality Index (PSQI) |
| Absence or presence of inflammation of target hand | Week 16 | Change in absence or presence of inflammation of the target hand as measured by ultrasound (US) |
| Change in use of analgesics | Week 16 | Change in use of analgesics measured as the use of paracetamol and NSAIDS |
Countries
Denmark
Contacts
Primary ContactKasper Staberg Madsen
Outcome results
None listed