Systemic SclerosisPhase 1NCT02981082
Dimethyl Fumarate (DMF) in Systemic Sclerosis-Associated Pulmonary Arterial Hypertension
A Phase 1 study testing Dimethyl Fumarate (DMF) in people with Systemic Sclerosis and Pulmonary; Hypertension, run by Robert Lafyatis at 4 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Systemic Sclerosis, Pulmonary; Hypertension
- What is being tested?
- Dimethyl Fumarate (DMF)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 6 participants
- Where
- 4 sitesUnited States
- Study dates
- Dec 2016to 10 Feb 2020
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Signed inform consent prior to any study-mandated procedures
- Adult patients 18-80 years of age
- World Health Organization Group 1 PAH associated with scleroderma (SSc-PAH)
- WHO functional Class II-III
- 6MWD 150 to 450 meters
- 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.
- ACR defined systemic sclerosis
Who cannot join
- 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
Show all 19Show fewer
- Sarcoidosis
- Participation in a clinical investigational study within the previous 30 days
- Moderate to severe hepatic impairment (e.g., Child-Pugh Class B or C)
- Renal failure defined as:
- estimated creatinine clearance <30 m/min
- serum creatinine>2.5 mg/dl
- Serum aspartate aminotransferase (AST) and or alanine aminotransferase (ALT) > 1.5 times the upper limit of normal
- Systolic blood pressure < 90mmHg
- Recently started (< 8 weeks prior to randomization) or planned cardiopulmonary rehabilitation program based on exercise
- Pregnant or lactating women
- Need for HAART therapy
- Planned treatment or treatment with another investigational drug within 1 month prior to start
- 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
Trial locations and contacts
4 sites in 1 country.
United States4 sites
John Hopkins
Baltimore, Maryland, 21205
Boston University
Boston, Massachusetts, 02118
National Jewish
Denver, Colorado, 80206
University of Pittsburgh
Pittsburgh, Pennsylvania, 15213
About this study
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.
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).
Read the 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).
- Conditions
- Systemic Sclerosis, Pulmonary; Hypertension
- Being tested
- Dimethyl Fumarate (DMF), Placebo Oral Tablet
- Keywords
- Systemic Sclerosis, Scleroderma, PAH, Pulmonary Hypertension
- Medical subject headings
- Scleroderma, Systemic, Hypertension, Pulmonary, Scleroderma, Diffuse
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dimethyl Fumarate (DMF)Drug
Also called Tecfidera
Dimethyl Fumarate (DMF) is a prescription medicine used to treat relapsing multiple sclerosis.
Placebo Oral TabletDrug
Sugar pill manufactured to mimic Dimethyl Fumarate (DMF)
| Study group | Role | What they receive |
|---|---|---|
| Dimethyl Fumarate (DMF) | Active comparator | 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 Receives: Drug: Dimethyl Fumarate (DMF) |
| Placebo | Placebo comparator | Twice daily oral doses of placebo for 12 weeks Receives: Drug: Placebo Oral Tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
6 Minute Walk Distance (6MWD)
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.
Measured: Baseline to Week 24
Secondary outcomes (4)
Clinical Worsening
The change in time to clinical worsening in DMF compared to placebo treated patients.
Measured: Baseline to Week 24
Borg Dyspnea Index (BDI)
The change in Borg Dyspnea Index (BDI) at 24 weeks from baseline in DMF compared to placebo treated patients
Measured: Baseline to Week 24
Serum Markers of Oxidative Stress
The change from baseline of serum markers of oxidative stress at 24 weeks, comparing DMF to placebo treated patients.
Measured: Baseline to Week 24
Proteomic Biomarkers
The change from baseline in proteomic biomarkers, including BNP, at 24 weeks, comparing DMF to placebo treated patients.
Measured: Baseline to Week 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Dec 2016 (estimated)
- Study startDec 2016
- Primary completion10 Feb 2020
- Study completion10 Feb 2020
Why it stopped: Low recruitment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Systemic SclerosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- Robert Lafyatis
- Sponsor type
- University, hospital or other
- Collaborators
- Biogen
- Responsible party
- Sponsor-investigator, Robert Lafyatis, University of Pittsburgh
- Investigators
- Robert A Lafyatis, MD, Principal investigator, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02981082
- Sponsor's protocol ID
- PRO16070614
- Status last verified
- Mar 2022
- First submitted
- 30 Nov 2016
- Last updated
- 17 Mar 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 17 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT02981082
- Acronym / sponsor ID
- PRO16070614
- Conditions
- Systemic Sclerosis, Pulmonary; Hypertension
- Keywords
- Systemic Sclerosis, Scleroderma, PAH, Pulmonary Hypertension
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Low recruitment
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Robert LafyatisUniversity, hospital or other
- Collaborators
- Biogen
- Study start
- Dec 2016
- Primary completion
- 10 Feb 2020 (actual)
- Study completion
- 10 Feb 2020 (actual)
- First posted
- 2 Dec 2016 (estimated)
- Results
- Posted 17 Mar 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Dimethyl Fumarate (DMF) | Active comparator | Drug: 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 |
| Placebo | Placebo comparator | Drug: Placebo Oral TabletTwice daily oral doses of placebo for 12 weeks |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Signed inform consent prior to any study-mandated procedures
- Adult patients 18-80 years of age
- World Health Organization Group 1 PAH associated with scleroderma (SSc-PAH)
- WHO functional Class II-III
- 6MWD 150 to 450 meters
Key exclusion criteria (19 listed)
- Pulmonary hypertension associated with
- Participation in a clinical investigational study within the previous 30 days
- Moderate to severe hepatic impairment (e.g., Child-Pugh Class B or C)
- Renal failure defined as:
- Serum aspartate aminotransferase (AST) and or alanine aminotransferase (ALT) > 1.5 times the upper limit of normal
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Dimethyl Fumarate (DMF)Also: TecfideraDimethyl Fumarate (DMF) is a prescription medicine used to treat relapsing multiple sclerosis. | Drug | Dimethyl Fumarate (DMF) |
| Placebo Oral TabletSugar pill manufactured to mimic Dimethyl Fumarate (DMF) | Drug | Placebo |
Primary outcome
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.
4 secondary outcomes
Clinical Worsening
Time frame: Baseline to Week 24
Borg Dyspnea Index (BDI)
Time frame: Baseline to Week 24
Serum Markers of Oxidative Stress
Time frame: Baseline to Week 24
Proteomic Biomarkers
Time frame: Baseline to Week 24
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Mar 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Undecided
Related trials for Systemic Sclerosis
Not yet recruitingPhase 2
Hyaluronidase Injections for Sclerodactyly in Patients With Scleroderma
Scleroderma, Sclerodactyly
RecruitingPhase 1
A Trial in Healthy Adult Participants and Adults With Autoimmune Diseases to Test How HBM7020 is Tolerated and How it Behaves in the Body
Rheumatoid Arthritis, Systemic Lupus Erythematosus
Active, not recruitingPhase 2
A Study Evaluating the Safety and Efficacy of Inhaled AP01 in Participants With Progressive Pulmonary Fibrosis
Pulmonary Fibrosis, Progressive Pulmonary Fibrosis
RecruitingObservational study
Quantification of Calcinosis Cutis Disease Burden Using Computed Tomography Images
Systemic Sclerosis (SSc), Calcinosis Cutis
RecruitingPhase 1/2
Phase I/II Study of AD-PluReceptor Plus Tafasitamab-cxix and Lymphodepleting Chemotherapy in Patients With Autoimmune Disorders
Autoimmune Disorders, Systemic Sclerosis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Robert A Lafyatis, MD principal investigator
University of Pittsburgh
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Dimethyl Fumarate (DMF) in people with Systemic Sclerosis and Pulmonary; Hypertension, run by Robert Lafyatis at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 17 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Mar 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
6 Minute Walk Distance (6MWD) (time frame: Baseline to Week 24). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Mar 2022.