Divalproex Sodium in the Treatment of the Cutaneous Manifestations of Scleroderma

Phase 1

Withdrawn

• Conditions: Scleroderma; Systemic Sclerosis
• Interventions: Drug: Divalproex sodium

• Registration Number: NCT02166229
• Lead Sponsor: Yale University

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2014-06
• Study First Submitted: 2014-06-10
• Study First Submitted QC: 2014-06-13
• Study First Posted: 2014-06-18
• Primary Completion: 2014-08
• Study Completion: 2014-08
• Status Verified: 2016-08
• Last Update Submitted: 2016-08-10
• Last Update Posted: 2016-08-11

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Divalproex sodium	Divalproex sodium	Divalproex sodium will be initiated at 125 mg twice daily and increased monthly to a maximum dose of 500 mg twice daily.

Primary Outcome Measures

Name	Time	Method
Number of new digital ulcers	12 months

Secondary Outcome Measures

Name	Time	Method
Change in estimated affected total body surface area	12 months
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 modified Rodnan skin score	12 months
Change in digital circumference	12 months
Change in maximum oral aperture	12 months
Scleroderma Health Assessment Questionnaire (SHAQ)	12 months
Number of new lesions of calcinosis cutis	12 months

Trial Locations

Locations (1)

Yale University; 🇺🇸 New Haven, Connecticut, United States