Divalproex Sodium in the Treatment of the Cutaneous Manifestations of Scleroderma

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.

Study Overview

• Status: Withdrawn
• Conditions: Systemic Sclerosis; Scleroderma
• Intervention / Treatment: Drug: Divalproex sodium

• Study Type: Interventional
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Divalproex sodium; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Yale University
• Investigators: Principal Investigator: Brett King, MD, PhD, Yale University

Study record dates

Study Major Dates

• Study Start: June 1, 2014
• Primary Completion (Actual): August 1, 2014
• Study Completion (Actual): August 1, 2014

Study Registration Dates

• First Submitted: June 10, 2014
• First Submitted That Met QC Criteria: June 13, 2014
• First Posted (Estimate): June 18, 2014

Study Record Updates

• Last Update Posted (Estimate): August 11, 2016
• Last Update Submitted That Met QC Criteria: August 10, 2016
• Last Verified: August 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Connective Tissue Diseases; Scleroderma, Systemic; Scleroderma, Diffuse; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Enzyme Inhibitors; Tranquilizing Agents; Psychotropic Drugs; GABA Agents; Anticonvulsants; Antimanic Agents; Valproic Acid
• Other Study ID Numbers: 1404013775