Hand Osteoarthritis
Conditions
Keywords
Symptomatic hand osteoarthritis (HOA), Clobetasol propionate
Brief summary
This is a randomized, double-blind, comparative trial evaluating the efficacy on pain intensity between topical Clobetasol Propionate 0.05% and placebo in patients with symptomatic hand osteoarthritis.
Detailed description
Symptomatic hand osteoarthritis (HOA) affects 8-16% of the $general population. It includes joint pain and functional disability, inducing a substantial daily burden. Half of patients have an inflammatory HOA, characterized by the presence of synovitis at interphalangeal (IP) joint which is associated with an increased risk of pain (OR joint pain=2.4 IC95% (1.6-3.8)) and loss of function than in those without inflammatory HOA. Systemic symptomatic pharmacological treatments of HOA are either poorly effective (ie, paracetamol) or tolerated (ie, oral non-steroidal anti-inflammatory drugs (NSAIDs)) in this elderly population. Studies evaluating systemic drugs (TNF or IL6 inhibitors) failed to show symptomatic efficacy in inflammatory HOA except for oral corticosteroids but with potential severe side effects. In 2018, EULAR recommended topical treatments over systemic ones for safety issues. Topical NSAIDs are the 1st choice despite modest efficacy, with only 1 randomized placebo-controlled trial showing a significant but modest 7.2 mm difference over placebo on 0-100 mm visual analog scale (VAS) pain at week 4. Other topics such as capsaicin have not relevant efficacy or were not specifically studied in HOA. Therefore, innovative topical pharmacological approaches greater than topical NSAIDs are awaited to treat HOA pain with a good safety profile. The application of a topical corticosteroid, rather than a systemic one, could improve pain in inflammatory HOA, with a better benefit/risk profile. In 2023, betamethasone in optimized vehicle (Diprosone OV 0.05%) showed no superiority over control on pain and function in HOA. Noteworthy however, despite an anti-inflammatory effect, 1) the presence of synovitis was not required at inclusion for HOA patients while corticoids target inflammation and thus pain 2) Bethamethasone dipropionate (Diprosone) is not the most powerful dermocorticoid (class II)-3) Of the 4 levels of activity, clobetasol propionate 0.05% has the most powerful anti-inflammatory action (class I). The investigators hypothesize that topical clobetasol propionate 0.05% which has the most powerful anti-inflammatory action (class I) could reduce pain in patients with inflammatory HOA (defined by the presence of ≥2 clinical and ultrasound synovitis) with a good safety profile.
Interventions
DRUGPropionate de Clobétasol ( 0.05 %)
From D0-D28 a dose of cream (Clobetasol Propionate 0.05%) will be applied twice a day for 2 weeks then once a day for 2 weeks on painful joints with the maximum dose being the equivalent of a phalanx unit corresponding to the quantity of cream taken out of the tube and last deposited over the entire length of the phalanx of the index finger.
DRUGPlacebo
From D0-D28 a dose of cream (Placebo) will be applied twice a day for 2 weeks then once a day for 2 weeks on painful joints with the maximum dose being the equivalent of a phalanx unit corresponding to the quantity of cream taken out of the tube and last deposited over the entire length of the phalanx of the index finger.
Sponsors
Assistance Publique - Hôpitaux de Paris
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
45 Years to No maximum
Healthy volunteers
No
Inclusion criteria
To be eligible for enrollment, an individual must meet all of the following criteria. * Age ≥ 45 years * Symptomatic HOA according to the American College of Rheumatology criteria \[10\] * EVA ≥ 40/100 in the last 48 hours. * Presence of hand pain for at least 15 days in the last 30 days * At least ≥2 symptomatic IP joint with clinical palpable synovitis at inclusion. * Informed written consent * Prior treatment failure (inadequate response or intolerance to at least 1 recommended treatment among paracetamol, topical or oral NSAIDs, or short course of corticosteroids) * Patient affiliated to a social security scheme
Exclusion criteria
: Patients will be excluded from participating in the study if they meet or are expected to meet any of the following criteria. * Isolated or predominant painful thumb-base OA (i.e., rhizarthrosis) * Other inflammatory joint disease (e.g. gout, reactive arthritis, rheumatoid arthritis, psoriatic arthritis, seronegative spondyloarthropathy, Lyme disease) * Current skin abnormality, irritation, or lesions of the hands (e.g., eczema, urticarial lesion, skin infection) contraindicating topical application * Contraindication to propionate clobetasol * Existence of a pain syndrome of the upper limbs, which would interfere with the monitoring of pain * Fibromyalgia * Use of oral, intramuscular or intra-articular or intravenous steroids, other anti-synovial agents (e.g. slow-acting anti-rheumatic drugs such as methotrexate, sulfasalazine), intra-articular hyaluronic acid to the hand joints within the 1 month prior to the inclusion visit (W0) * Use of oral NSAIDs or paracetamol less than 48h before the inclusion visit (W0) * Any topical treatment (corticosteroids included) on treated extremities for any indication, other than cosmetic use of creams and lotions, within the 2 weeks prior to the inclusion visit (W0). * Any new hand OA treatment within the 2 months prior to the inclusion visit (W0), including physiotherapy and provision of new hand splint. * Use of opioids within the 4 weeks (or the equivalent of 5 half-lives) prior to the inclusion visit (W0) * Planned hand surgery in the next 6 weeks. * Use of any investigational (unlicensed) drug within the 3 months prior to the inclusion visit (W0). * History of glaucoma contraindicating the use of corticosteroids. * Presence of a serious, uncontrolled concomitant cardiovascular, pulmonary, renal, hepatic, endocrine, gastrointestinal, neurological (including epilepsy) condition which, according to the investigator, makes the patient ineligible for the study. * Systemic progressive infection * Pregnant or breastfeeding woman * Patient under legal protection measure (tutorship or curatorship) and patient deprived of freedom * Patient is unable to apply the study drug on hands * Participation in another interventional study or being in the exclusion period at the end of a previous study. * Patient on AME (state medical aid)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in pain intensity between W0 and W4 | Week 0- Week 4 | Self-reported hand pain in the previous 48h measured on a 100 mm VAS at W0 and W4. The measurement will be done with the standard question recommended by Osteoarthritis Research Society International (OARSI) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Hand pain improvement | Week 0- week 4 | Change in pain intensity between W0 and W4 (W4-W0) of AUSCAN (Australian/Canadian Osteoarthritis Hand Index) pain subscore 0 = no difficulty 1. = mild difficulty 2. = moderate difficulty 3. = significant difficulty 4. = extreme difficulty |
| Hand function at week 4 | Week 0 - Week 4 | Change between W0 and W4 (W4-W0) in the following endpoints: * AUSCAN (Australian/Canadian Osteoarthritis Hand Index), function subscore * Functional Index for Hand Osteoarthritis (FIHOA) score 0 = possible without difficulty 1. = possible with moderate difficulty 2. = possible with significant difficulty 3. = impossible |
| Stiffness improvement at Week 4 | Week 0 - Week 4 | Change between W0 and W4 (W4-W0) in the following endpoints: \- AUSCAN, stiffness subscore 0 = no difficulty 1. = mild difficulty 2. = moderate difficulty 3. = significant difficulty 4. = extreme difficulty |
| Treatment response and satisfaction at Week 4 | Week 0 - Week 4 | * Proportion of patients' responders according to the Patient global impression of change (PGIC) * Proportion of patients below the Patient Acceptable Symptom State of pain (VAS\<40/100) * Proportion of OMERACT-OARSI (Outcome Measures in Rheumatology - Osteoarthritis Research Society International ) responders adapted to hand OA |
| Quality of life improvement | Week 0 - Week 4 | Change between W0 and W4 in: * EQ-5D-5L index score (-0.53 to 1.00) and EQ VAS score (0-100) from the EQ-5D-5L questionnaire * EQ-5D-5L Global health status |
| Safety assessment | Week2, Week4 and Week 8 | Proportion of side effects overall |
| Patient compliance | Week 0 -Week 04 | Quantity of cream (g) used between W0 and W4 (indirectly assessed by the weight change of the cream tube). |
Countries
France
Contacts
CONTACTAlice COURTIES, MD
CONTACTJérémie SELLAM, MD
PRINCIPAL_INVESTIGATORAlice COURTIES, MD
Assistance Publique - Hôpitaux de Paris
Outcome results
None listed