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

March 15, 2022 updated by: Robert Lafyatis

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.

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).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 begin at once daily oral doses of 120mg for the first 7 days and follow the up-titration schedule to a maintenance dose of 240mg twice a day (or highest tolerated dose of a minimum of 120mg twice a day by the start of Week 8) for the remainder of the study. 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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
6

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Colorado
      • Denver, Colorado, United States, 80206
        • National Jewish
    • Maryland
      • Baltimore, Maryland, United States, 21205
        • John Hopkins
    • Massachusetts
      • Boston, Massachusetts, United States, 02118
        • Boston University
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15213
        • University of Pittsburgh

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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 Names:
  • 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)

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
6 Minute Walk Distance (6MWD)
Time Frame: Baseline to Week 24
The primary outcome of clinical efficacy in this study is improvement in 6-minute walk distance (6MWD). Data depict the mean change (%) at end-of-study-treatment (Week 24) from baseline in both treatment groups, utilizing the Last Observation Carried Forward of withdrawn subjects.
Baseline to Week 24

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Clinical Worsening
Time Frame: Baseline to Week 24
The change in time to clinical worsening in DMF compared to placebo treated patients.
Baseline to Week 24
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
Baseline to Week 24
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.
Baseline to Week 24
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.
Baseline to Week 24

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Robert Lafyatis

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Biogen

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Robert A Lafyatis, MD, University of Pittsburgh

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 1, 2016

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 10, 2020

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 10, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 30, 2016

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 30, 2016

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 2, 2016

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 17, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 15, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • PRO16070614

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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