Divalproex Sodium in the Treatment of the Cutaneous Manifestations of Scleroderma

Study Overview
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Brief Summary
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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.

Conditions
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Scleroderma, Systemic Sclerosis

Intervention / Treatment
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* Drug: Divalproex sodium


Participation Criteria
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Eligibility Criteria
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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.

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Divalproex sodium<br>Divalproex sodium will be initiated at 125 mg twice daily and increased monthly to a maximum dose of 500 mg twice daily. | Drug: Divalproex sodium<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of new digital ulcers |  | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in modified Rodnan skin score |  | 12 months | 
| Change in digital goniometry measurements | Goniometry measures range of motion of joints and, in this study, will include measurements of the metacarpophalangeal, proximal interphalangeal, distal interphalangeal and wrist joints. | 12 months | 
| Change in hydraulic pinch and hand-grip strength measurements |  | 12 months | 
| Change in digital circumference |  | 12 months | 
| Change in maximum oral aperture |  | 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 |