ClinicalTrials.gov
ClinicalTrials.gov Menu

Dimethyl Fumarate (DMF) in Systemic Sclerosis-Associated Pulmonary Arterial Hypertension

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02981082
Recruitment Status : Recruiting
First Posted : December 2, 2016
Last Update Posted : December 7, 2018
Sponsor:
Collaborator:
Biogen
Information provided by (Responsible Party):
Robert Lafyatis, University of Pittsburgh

Brief 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).

Condition or disease Intervention/treatment Phase
Systemic Sclerosis Pulmonary; Hypertension Drug: Dimethyl Fumarate (DMF) Drug: Placebo Oral Tablet Phase 1

Detailed Description:
A double-blinded, placebo-controlled study of Dimethyl fumarate (DMF) in 34 Systemic Sclerosis-Pulmonary Hypertension (SSc‐PAH) patients. The study medication will be added to stable background PAH medication(s). Subjects will be dosed for 24 weeks, will undergo examination every 8 weeks, and will be finally evaluated 12 weeks after completion of treatment. Dosage will be twice daily oral doses of 120mg for the first 7 days followed by the maintenance dose of 240mg twice a day.Participation will be for a total of 40 weeks, including a 4-week screening period, 24 weeks of drug, and a safety follow‐up 12 weeks after the last dose. The study will determine the 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).

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 34 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Double-blinded, Placebo-controlled Pilot Study of Dimethyl Fumarate (DMF) in Pulmonary Arterial Hypertension (PAH) Associated With Systemic Sclerosis (SSc-PAH): The Effect of DMF on Clinical Disease and Biomarkers of Oxidative Stress.
Study Start Date : December 2016
Estimated Primary Completion Date : November 2019
Estimated Study Completion Date : May 2020


Arm Intervention/treatment
Active Comparator: Dimethyl Fumarate (DMF)
Twice daily oral doses of Dimethyl Fumarate (DMF) 120mg for the first 7 days followed by the maintenance dose of Dimethyl Fumarate (DMF) 240mg twice a day. Subjects will be dosed for 24 weeks
Drug: Dimethyl Fumarate (DMF)
Dimethyl Fumarate (DMF) is a prescription medicine used to treat relapsing multiple sclerosis.
Other Name: Tecfidera

Placebo Comparator: Placebo
Twice daily oral doses of placebo for 12 weeks
Drug: Placebo Oral Tablet
Sugar pill manufactured to mimic Dimethyl Fumarate (DMF)




Primary Outcome Measures :
  1. 6 minute walk distance (6MWD). [ Time Frame: Baseline to Week 24 ]
    The primary outcome of clinical efficacy in this study will be improvement in 6‐minute walk distance (6MWD).


Secondary Outcome Measures :
  1. Clinical Worsening [ Time Frame: Baseline to Week 24 ]
    The change in time to clinical worsening in DMF compared to placebo treated patients.

  2. Borg Dyspnea Index (BDI) [ Time Frame: Baseline to Week 24 ]
    The change in Borg Dyspnea Index (BDI) at 24 weeks from baseline in DMF compared to placebo treated patients

  3. Serum markers of oxidative stress [ Time Frame: Baseline to Week 24 ]
    The change from baseline of serum markers of oxidative stress at 24 weeks, comparing DMF to placebo treated patients.

  4. Proteomic biomarkers [ Time Frame: Baseline to Week 24 ]
    The change from baseline in proteomic biomarkers, including BNP, at 24 weeks, comparing DMF to placebo treated patients.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02981082


Contacts
Contact: Robert A Lafyatis, MD 412-383-9045 lafyatis@pitt.edu

Locations
United States, California
Stanford University Not yet recruiting
Stanford, California, United States, 94305
Contact: Dina Jean    650-725-9861    Dina.jean@stanford.edu   
Principal Investigator: Roham Zamanian, MD         
United States, Colorado
National Jewish Not yet recruiting
Denver, Colorado, United States, 80206
Contact: Kris Eliopoulos    303-270-2622    eliopoulosk@njhealth.org   
Principal Investigator: Patricia George, MD         
United States, Maryland
John Hopkins Not yet recruiting
Baltimore, Maryland, United States, 21205
Contact: Blessing Enobun    410-502-4362    benobun1@jhu.edu   
Principal Investigator: Paul Hassoun, MD         
United States, Massachusetts
Boston University Recruiting
Boston, Massachusetts, United States, 02118
Contact: Eric Stratton    617-358-6777    eas@bu.edu   
Contact: Kim Finch    617-358-6785    kimtobin@bu.edu   
Principal Investigator: Robert Simms, MD         
United States, Michigan
University of Michigan Not yet recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Ann Green    866-963-3587    johnsann@med.umich.edu   
Contact: Cindy Alsamarraie    866-963-3587    sindi@med.umich.edu   
Principal Investigator: Vallerie McLaughlin, MD         
United States, Pennsylvania
University of Pittsburgh Recruiting
Pittsburgh, Pennsylvania, United States, 15213
Contact: Dana Ivanco, BA, CCRC    412-648-7040    des2@pitt.edu   
Contact: Maureen Laffoon, BS    412-648-7871    laffoonm@pitt.edu   
Principal Investigator: Robert A Lafyatis, MD         
Sponsors and Collaborators
Robert Lafyatis
Biogen
Investigators
Principal Investigator: Robert A Lafyatis, MD University of Pittsburgh

Responsible Party: Robert Lafyatis, Professor of Medicine and the Thomas Medsger Professor in Arthritis Research, University of Pittsburgh
ClinicalTrials.gov Identifier: NCT02981082     History of Changes
Other Study ID Numbers: PRO16070614
First Posted: December 2, 2016    Key Record Dates
Last Update Posted: December 7, 2018
Last Verified: December 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by Robert Lafyatis, University of Pittsburgh:
Systemic Sclerosis, Scleroderma, PAH, Pulmonary Hypertension

Additional relevant MeSH terms:
Scleroderma, Systemic
Scleroderma, Diffuse
Hypertension
Sclerosis
Familial Primary Pulmonary Hypertension
Hypertension, Pulmonary
Vascular Diseases
Cardiovascular Diseases
Pathologic Processes
Lung Diseases
Respiratory Tract Diseases
Connective Tissue Diseases
Skin Diseases
Dimethyl Fumarate
Dermatologic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs