Scleroderma, Systemic Sclerosis
Conditions
Brief summary
To investigate the ability of divalproex sodium, a histone deacetylase inhibitor, to improve the digital manifestations of scleroderma including digital edema, calcinosis cutis, digital ulcers, and joint contractures.
Interventions
DRUGDivalproex sodium
Sponsors
Yale University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 18 years of age or older * Diagnosis of scleroderma as defined by the American College of Rheumatology (ACR) * Presence of at least one digital manifestation occurring within the past 6 months, i.e. digital swelling/edema, digital ulcer, calcinosis cutis, restricted digital range of motion. * Females of childbearing potential must take an oral contraceptive pill or use an equivalent birth control method during the study.
Exclusion criteria
* Age \<18 years old * Ongoing use of high dose steroids (\>10 mg/day) or unstable steroid dose in past 4 weeks. * An investigational drug or disease-modifying agent has been started within the past 6 months, including but not limited to systemic corticosteroids, methotrexate, cyclosporine, azathioprine, cyclophosphamide, bosentan, mycophenolate mofetil, thalidomide, colchicine. * Patient taking a medication with a significant drug-drug interaction with divalproex sodium, e.g. clomipramine and lamotrigine. * Patient has another connective tissue disease or other condition that could affect rest pain and hand function, e.g. systemic lupus erythematosus, rheumatoid arthritis, or osteoarthritis. * Patient has uncontrolled diabetes, chronic kidney disease, chronic hepatitis. * Any of the following laboratory abnormalities at baseline: anemia (Hb \< 8.5 gm/dL), thrombocytopenia with platelets \<100,000, INR \> 1.3 or known bleeding disorder, estimated GFR \< 60 mL/min/1.73m2 or serum creatinine \> 2.0 mg/dL, hyperbilirubinemia or elevation of AST or ALT * Pregnancy or breast-feeding. * History of severe depression (i.e. depression requiring medical treatment by a psychiatrist), suicidal ideation, epilepsy, bipolar disorder, or schizophrenia.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of new digital ulcers | 12 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in digital goniometry measurements | 12 months | Goniometry measures range of motion of joints and, in this study, will include measurements of the metacarpophalangeal, proximal interphalangeal, distal interphalangeal and wrist joints. |
| Change in hydraulic pinch and hand-grip strength measurements | 12 months | — |
| Change in digital circumference | 12 months | — |
| Change in modified Rodnan skin score | 12 months | — |
| Change in estimated affected total body surface area | 12 months | — |
| Scleroderma Health Assessment Questionnaire (SHAQ) | 12 months | — |
| Number of new lesions of calcinosis cutis | 12 months | — |
| Change in maximum oral aperture | 12 months | — |
Countries
United States
Outcome results
None listed