Colchicine as Treatment for People With Hand Osteoarthritis

Study Overview
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Brief Summary
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The study aims to compare oral colchicine 0.5 mg administered two times daily for 12 weeks with placebo as a treatment of hand OA symptoms.

Official Title
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Colchicine Treatment for Patients With Hand Osteoarthritis: A Randomised, Placebo-controlled Trial.

Conditions
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Osteoarthritis Hand, Osteoarthritis Finger

Intervention / Treatment
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* Drug: Colchicine 0.5 MG
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years. Hand OA according to the ACR criteria above. Hand OA finger pain: Pain at rest ≥40 mm on VAS (0 to 100 mm range). Exclusion Criteria: Comorbidities Other known medical disease that may affect joints, e.g. RA, gout, PsA Positive anti-cyclic citrullinated peptide (>10 kU/L) Known cutaneous deposition diseases (e.g. amyloidosis or porphyria). Known blood dyscrasias and coagulation disorders Known malignancy (except successfully treated squamous or basal cell skin carcinoma) Elevated alanine transaminase (>45 U/L females, >70 U/L for males) Creatinine clearance ≤60 ml/min Elevated creatine kinase (>210 U/L females, >280 U/L for males) Known allergies towards the interventions Drug or alcohol abuse in the last year Generalised pain syndromes such as fibromyalgia Current reflux Current or recurrent diarrhoeal illnesses Current abdominal pain Known peripheral neuropathies Any other condition or impairment that, in the opinion of the investigator, makes a potential participant unsuitable for participation or which obstruct participation, such as e.g. psychiatric disorders. Medical history History of hand surgery within 12 months prior enrolment. History of arthroplasty or arthrodesis in the hand Management strategies Treatment with P-glycoprotein inhibitors and/or cytochrome P450 3A4 (CYP3A4) inhibitors, see section Colchicine safety in drug-drug interactions and table 7. If potential participants have been treated with these pharmaceuticals previously, treatment must be terminated 5 half-lifes before initiation of study drug. Use of systemic corticosteroids equivalent of ≥ 7.5 mg prednisolone daily within 3 months. Participation in experimental device or experimental drug study 3 months prior to enrolment. Intra-articular treatments or aspirations of any kind of any joint in the hands 3 months before inclusion Intra-articular corticosteroids into any joint 1 months before inclusion Current use of synthetic or non-synthetic opioids Scheduled surgery during study participation Planning to start other treatment for hand OA in the study participation period. Reproductive system Pregnancy. 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. 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. Menopause state will be confirmed by measurement of follicle stimulating hormone. 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). Breast-feeding A target hand will be selected for outcome assessment once individual fulfills in- and exclusions criterias. Selection of the target hand will adhere to the following, with advancement to next step if unable to choose target hand based on the given criteria. The hand with most overall pain, assessed by VAS finger joint pain. The hand with most overall reduced function, assessed by AUSCAN function subscale. The hand with most overall stiffness, assessed by AUSCAN stiffness subscale. The hand with most swollen joints, assessed by physician joint count. The hand with most tender joints, assessed by physician joint count. The hand with highest summed radiographic score, assessed by radiographic scoring of conventional X-ray. If unable to select target hand based on the above criteria, a target hand will be randomly assigned.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Colchicine<br>Tablet colchicine 0.5 mg administered two times daily | Drug: Colchicine 0.5 MG<br>* The intervention tablets are commercially available Colchicine Tiofarma<br>|
| Placebo Comparator: Placebo<br>Tablet placebo administered two times daily | Drug: Placebo<br>* Encapsulated placebo tablets. Placebo is identical to the active intervention.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Finger pain | To compare the effect of oral colchicine 0.5 mg bid, relative to placebo, on changes in finger joint pain of the target hand from baseline to week 12, in patients with painful hand OA measured on a visual analogue scale spanning from 0 to 100, where 0 equals no symptoms and 100 equals worst imaginable symptoms. | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Function | To compare the effect of oral colchicine 0.5 mg bid, relative to placebo, from baseline to week 12, in patients with painful hand OA on changes in function of both hands measured on the Australian/Canadian Hand Index Function Score spanning from 0 to 900, where higher scores equals worse function. | Week 12 | 
| Thumb base pain | To compare the effect of oral colchicine 0.5 mg bid, relative to placebo, from baseline to week 12, in patients with painful hand OA on changes in thumb base pain of the target hand measured on a visual analogue scale spanning from 0 to 100, where 0 equals no symptoms and 100 equals worst imaginable symptoms. | Week 12 | 
| Pain hands | To compare the effect of oral colchicine 0.5 mg bid, relative to placebo, from baseline to week 12, in patients with painful hand OA on changes in pain of both hands measured on the Australian/Canadian Hand Index Pain Score spanning from 0 to 500, where higher scores equals worse pain. | Week 12 | 
| Joint activity | To compare the effect of oral colchicine 0.5 mg bid, relative to placebo, from baseline to week 12, in patients with painful hand OA on changes in joint activity of the target hand measured on physician tender joint count | Week 12 | 
| Patient global assessment | To compare the effect of oral colchicine 0.5 mg bid, relative to placebo, from baseline to week 12, in patients with painful hand OA on changes in patient global assessment measured on a visual analogue scale spanning from 0 to 100, where 0 equals no symptoms and 100 equals worst imaginable symptoms. | Week 12 | 
| Quality of life measured by European Quality of Life 5 Dimensions | To compare the effect of oral colchicine 0.5 mg bid, relative to placebo, from baseline to week 12, in patients with painful hand OA on changes in quality of life measured on the European Quality of Life 5 Dimensions spanning from -0.624 to 1.000, where higher scores equals better quality of life. | Week 12 | 
| Hand strength | To compare the effect of oral colchicine 0.5 mg bid, relative to placebo, from baseline to week 12, in patients with painful hand OA on changes in hand strength of the target hand measured on grippit | Week 12 | 
| Number of treatment responders according to OMERACT-OARSI response criteria | The following two conditions is observed at the post-baseline assessment: In either pain (finger pain) or function (function), a high improvement in the subscale, where high improvement in a subscale is achieved if there is both a > 50% improvement from Baseline and an absolute change from Baseline of > 20 percent points (0-100 scale), OR Improvement in at least two of the following three: Improvement in pain (finger pain) defined as > 20% improvement from Baseline and an absolute change from Baseline of > 10 points (0-100 scale) Improvement in function (function) defined as > 20% improvement from Baseline and an absolute change from Baseline of > 10 points (0-100 scale) Improvement in patient's global assessment defined as > 20% improvement from Baseline and an absolute change from Baseline of > 10 mm (0-100 scale) | Week 12 |