Dimethyl Fumarate (DMF) in Systemic Sclerosis-Associated Pulmonary Arterial Hypertension
Condition: Systemic Sclerosis; Pulmonary; Hypertension
MeSH terms: Pulmonary Arterial Hypertension; Hypertension, Pulmonary; Hypertension; Scleroderma, Systemic; Scleroderma, Diffuse; Sclerosis
Intervention: Dimethyl Fumarate (DMF); Placebo Oral Tablet
Intervention description: Dimethyl Fumarate (DMF) is a prescription medicine used to treat relapsing multiple sclerosis.; Sugar pill manufactured to mimic Dimethyl Fumarate (DMF)
Intervention MeSH terms: Dimethyl Fumarate
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 6.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: Systemic Sclerosis, Scleroderma, PAH, Pulmonary Hypertension

Summary:

      A double-blinded, placebo-controlled study of Dimethyl fumarate (DMF) in 34 Systemic
      Sclerosis-Pulmonary Hypertension (SSc-PAH) patients. The study will determine safety and the
      primary outcome variability for DMF in treating SSc-PAH; the primary outcome of clinical
      efficacy in this pilot trial will be improvement in 6-minute walk distance (6MWD).
    

Eligibility criteria:

        Inclusion Criteria:

          1. Signed inform consent prior to any study-mandated procedures

          2. Adult patients 18-80 years of age

          3. World Health Organization Group 1 PAH associated with scleroderma (SSc-PAH)

          4. WHO functional Class II-III

          5. 6MWD 150 to 450 meters

          6. Right heart catheterization demonstrating mPAP≥ 25 mmHg and PCWP or left ventricular
             end diastolic pressure ≤15mm Hg and pulmonary vascular resistance ≥240 dynes/cm-5 (3
             Wood units) within 12 weeks prior to study entry.

          7. ACR defined systemic sclerosis

        Exclusion Criteria:

          1. Pulmonary hypertension associated with

               -  PAH of any etiology other than scleroderma

               -  PH of any etiology other than WHO Group I PAH

               -  Pulmonary venous hypertension defined as PCWP or LVEDP >15 mHg

               -  Untreated sleep apnea with AHI >20 or SaO2 Nadir <87%

               -  Chronic thromboembolic disease

               -  Sarcoidosis

          2. Participation in a clinical investigational study within the previous 30 days

          3. Moderate to severe hepatic impairment (e.g., Child-Pugh Class B or C)

          4. Renal failure defined as:

               -  estimated creatinine clearance <30 m/min

               -  serum creatinine>2.5 mg/dl

          5. Serum aspartate aminotransferase (AST) and or alanine aminotransferase (ALT) > 1.5
             times the upper limit of normal

          6. Systolic blood pressure < 90mmHg

          7. Recently started (< 8 weeks prior to randomization) or planned cardiopulmonary
             rehabilitation program based on exercise

          8. Pregnant or lactating women

          9. Need for HAART therapy

         10. Planned treatment or treatment with another investigational drug within 1 month prior
             to start

         11. Moderate to severe interstitial lung disease, defined by FVC < 80% or evidence on HRCT
             of fibrosis or ground glass changes involving more than 30% of lung parenchyma