Raynaud's PhenomenonEarly Phase 1NCT02583789
Assess Efficacy of of Oral Treprostinil in Patients With Symptomatic Primary or Secondary Raynaud's Phenomenon
A Early Phase 1 study testing oral treprostinil in people with Raynaud's Phenomenon, run by Brigham and Women's Hospital at 1 site in United States.
Trial summary
This study represents the first trial to assess the efficacy of oral treprostinil therapy in patients with symptomatic primary or secondary Raynaud's Phenomenon (RP) resistant to vasodilatory therapy. The study will be randomized 1:1 UT-15C to placebo. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Raynaud's Phenomenon
- What is being tested?
- oral treprostinil
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- May 2016to 31 Dec 2021
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients aged ≥18-65 years
- Active Raynaud's Phenomenon defined as patients with refractory RP having four or more RP attacks per week in the 2 weeks before inclusion in the study despite treatment with vasodilators for at least 3 months
- Patients with primary Raynaud's Phenomenon
- Patients with Raynaud's secondary to connective tissue diseases (including scleroderma (SSc), limited scleroderma (CREST), mixed connective tissue disease (MCTD), primary Sjogren's syndrome (SS), systemic lupus erythematosus (SLE), with diagnosis of the underlying rheumatic disease based on standard criteria
- Patients on stable dose phosphodiesterase inhibitors (sildenafil, tadalafil or vardenafil), endothelin antagonists, alpha adrenergic antagonists, or calcium channel blockers defined as 3-months with no change in dose will be allowed to participate
Who cannot join
- Uncontrolled hypertension, diabetes mellitus, history of orthostatic hypotension, acute coronary or cerebrovascular event within 3 months, evidence of malignancy, history of sympathectomy
- Smoking within 3 months or smoking cessation using nicotine products
- Subjects currently taking or other prostacyclins.
- Pregnant or breast feeding or considering pregnancy in next 4 months
- Participation in trial with an investigational drug within 30 days
Trial locations and contacts
1 site in 1 country.
United States1 site
Brigham and Women's Hospital
Boston, Massachusetts, 02115
About this study
Official title: A Double-blinded, Placebo-controlled, Crossover Study to Assess Efficacy of Oral Treprostinil Titrated to Highest Tolerable Dose in 20 Patients With Symptomatic Primary or Secondary Raynaud's Phenomenon Resistant to Vasodilatory Therapy
This study represents the first trial to assess the efficacy of oral treprostinil therapy in patients with symptomatic primary or secondary Raynaud's Phenomenon (RP) resistant to vasodilatory therapy.
The study will be randomized 1:1 UT-15C to placebo. The design is a crossover study and all subjects will be randomized to receive oral treprostinil sustained release tablets or matching placebo for 12 weeks and then crossover for 12 weeks. All subjects will be exposed for 12 weeks of treatment with oral UT-15C during the study.
Read the detailed description
A single center double-blinded, placebo-controlled, crossover study to assess efficacy of oral treprostinil titrated to a tolerable goal dose of 2.0 mg three times per day (TID) in 20 patients with symptomatic primary or secondary Raynaud's Phenomenon resistant to vasodilatory therapy. Based on a pre-screening survey of the clinic population we anticipate at least 30 patients per year will be eligible for enrollment. At the clinicians discretion the dose can be increased as tolerated.
Eligible subjects at the time of signing an informed consent will have a diagnosis of primary or secondary Raynaud's Phenomenon. Subjects will be recruited from the Raynaud's Clinic, which is a multidisciplinary clinic held at the Watkins Clinic at the Shapiro Cardiovascular Center. Subjects will be assessed during a Screening and treatment initiation visit to determine eligibility for the study.
This study represents the first trial to assess the efficacy of oral treprostinil therapy in patients with symptomatic primary or secondary Raynaud's phenomenon resistant to vasodilatory therapy.
Oral treprostinil (UT-15C), a synthetic prostacyclin analog that inhibits platelet aggregation, induces vasodilation, and suppresses smooth muscle proliferation. In a recent open label study of escalating doses of oral treprostinil in patients with systemic sclerosis and digital ischemia, oral treprostinil was effectively absorbed in patients with scleroderma and was temporally associated with improved cutaneous perfusion and temperature. Thus, oral treprostinil may provide a new therapeutic option for patients with refractory secondary Raynaud's Phenomenon.
A recent systematic review demonstrated that oral calcium channel blockers, the most commonly prescribed drugs for primary RP, are only minimally effective in reducing the frequency of attacks and severity. Although Sildenafil has been shown to increase digital skin blood flow during all phases of local cooling in primary RP, its role in primary RP is not yet confirmed in randomized, controlled trials. To our knowledge, very few studies have assessed the use of oral prostacyclin therapy for disabling primary RP, although one multicenter, double-blind, randomized trial of an oral analog of prostacyclin, known as beraprost, reduced the number of RP attacks but proved no more beneficial than placebo.
- Conditions
- Raynaud's Phenomenon
- Being tested
- oral treprostinil, Placebo
- Medical subject headings
- Raynaud Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
oral treprostinilDrug
Also called Orenitram
Change in the Raynaud's Condition Score from baseline (2-week run in), comparing treprostinil treatment phase vs. placebo phase
PlaceboDrug
Also called Sugar pill
Placebo is a sugar pill manufactured to resemble UT-15C. Change in the Raynaud's Condition Score from baseline (2-week run in), comparing treprostinil treatment phase vs. placebo phase
| Study group | Role | What they receive |
|---|---|---|
| oral treprostinil | Active comparator | Dosing of oral treprostinil will be initiated at 0.125 mg three times daily. Dose escalations of oral treprostinil can occur every 72 hours (three consecutive doses) in 0.125 mg increments. Subjects will be titrated as tolerated to a goal dose of 2mg TID over a 6-week period. Receives: Drug: oral treprostinil; Drug: Placebo |
| Placebo | Placebo comparator | Placebo mimics oral treprostinil and will be taken three times a day Receives: Drug: oral treprostinil; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Raynaud's Condition Score
Change in the Raynaud's Condition Score from baseline (2-week run in), comparing treprostinil treatment phase vs. placebo phase
Measured: from baseline (2-week run in) to 6 weeks of treatment
Secondary outcomes (3)
Change in number of Raynaud's Phenomenon attacks
Change in the number of Raynaud's Phenomenon attacks per week during the sixth week of treatment phase compared to the number of Raynaud's Phenomenon attacks per week at baseline.
Measured: from baseline (2-week run in) to 6 weeks of treatment
Change in duration of Raynaud's Phenomenon attacks
Change in the total duration of Raynaud's Phenomenon attacks per week during the sixth week of treatment compared to the total duration of Raynaud's Phenomenon attacks per week at baseline.
Measured: from baseline (2-week run in) to 6 weeks of treatment
Reduction of ulcer burden among secondary Raynaud's Phenomenon patients
Decrease ulcer burden in secondary Raynaud's Phenomenon patients by reducing the time to heal active ulcers and/or reducing the number of new ulcers.
Measured: from baseline (2-week run in) to 6 weeks of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Oct 2015 (estimated)
- Study startMay 2016
- Primary completion31 Dec 2021
- Study completion31 Dec 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Raynaud's PhenomenonStudies of the same condition, open and under way.
- More trials run by Brigham and Women's HospitalThe sponsor's other registered studies.
- 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
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Brigham and Women's Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- United Therapeutics
- Responsible party
- Principal investigator, Aaron Waxman MD PhD, Brigham and Women's Hospital
- Investigators
- Aaron Waxman, MD/PhD, Principal investigator, Brigham and Womens HospitalPaul Dellaripa, MD, Principal investigator, Brigham and Womens Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02583789
- Sponsor's protocol ID
- 2015P001879
- Status last verified
- Jan 2022
- First submitted
- 8 Oct 2015
- Last updated
- 10 Jan 2022
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Ennis H, Hughes M, Anderson ME, Wilkinson J, Herrick AL. Calcium channel blockers for primary Raynaud's phenomenon. Cochrane Database Syst Rev. 2016 Feb 25;2(2):CD002069. doi: 10.1002/14651858.CD002069.pub5.
PubMed 26914257Roustit M, Hellmann M, Cracowski C, Blaise S, Cracowski JL. Sildenafil increases digital skin blood flow during all phases of local cooling in primary Raynaud's phenomenon. Clin Pharmacol Ther. 2012 May;91(5):813-9. doi: 10.1038/clpt.2011.302. Epub 2012 Mar 28.
PubMed 22453196Vayssairat M. Controlled multicenter double blind trial of an oral analog of prostacyclin in the treatment of primary Raynaud's phenomenon. French Microcirculation Society Multicentre Group for the Study of Vascular Acrosyndromes. J Rheumatol. 1996 Nov;23(11):1917-20.
PubMed 8923366
Study at a glance
From the registry record, last updated by the sponsor on 10 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Double-blinded, Placebo-controlled, Crossover Study to Assess Efficacy of Oral Treprostinil Titrated to Highest Tolerable Dose in 20 Patients With Symptomatic Primary or Secondary Raynaud's Phenomenon Resistant to Vasodilatory Therapy
- ClinicalTrials.gov ID
- NCT02583789
- Acronym / sponsor ID
- 2015P001879
- Conditions
- Raynaud's Phenomenon
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Brigham and Women's HospitalUniversity, hospital or other
- Collaborators
- United Therapeutics
- Study start
- May 2016
- Primary completion
- 31 Dec 2021 (actual)
- Study completion
- 31 Dec 2021 (actual)
- First posted
- 22 Oct 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study represents the first trial to assess the efficacy of oral treprostinil therapy in patients with symptomatic primary or secondary Raynaud's Phenomenon (RP) resistant to vasodilatory therapy.
The study will be randomized 1:1 UT-15C to placebo. The design is a crossover study and all subjects will be randomized to receive oral treprostinil sustained release tablets or matching placebo for 12 weeks and then crossover for 12 weeks. All subjects will be exposed for 12 weeks of treatment with oral UT-15C during the study.
Detailed description
A single center double-blinded, placebo-controlled, crossover study to assess efficacy of oral treprostinil titrated to a tolerable goal dose of 2.0 mg three times per day (TID) in 20 patients with symptomatic primary or secondary Raynaud's Phenomenon resistant to vasodilatory therapy. Based on a pre-screening survey of the clinic population we anticipate at least 30 patients per year will be eligible for enrollment. At the clinicians discretion the dose can be increased as tolerated.
Eligible subjects at the time of signing an informed consent will have a diagnosis of primary or secondary Raynaud's Phenomenon. Subjects will be recruited from the Raynaud's Clinic, which is a multidisciplinary clinic held at the Watkins Clinic at the Shapiro Cardiovascular Center. Subjects will be assessed during a Screening and treatment initiation visit to determine eligibility for the study.
This study represents the first trial to assess the efficacy of oral treprostinil therapy in patients with symptomatic primary or secondary Raynaud's phenomenon resistant to vasodilatory therapy.
Oral treprostinil (UT-15C), a synthetic prostacyclin analog that inhibits platelet aggregation, induces vasodilation, and suppresses smooth muscle proliferation. In a recent open label study of escalating doses of oral treprostinil in patients with systemic sclerosis and digital ischemia, oral treprostinil was effectively absorbed in patients with scleroderma and was temporally associated with improved cutaneous perfusion and temperature. Thus, oral treprostinil may provide a new therapeutic option for patients with refractory secondary Raynaud's Phenomenon.
A recent systematic review demonstrated that oral calcium channel blockers, the most commonly prescribed drugs for primary RP, are only minimally effective in reducing the frequency of attacks and severity. Although Sildenafil has been shown to increase digital skin blood flow during all phases of local cooling in primary RP, its role in primary RP is not yet confirmed in randomized, controlled trials. To our knowledge, very few studies have assessed the use of oral prostacyclin therapy for disabling primary RP, although one multicenter, double-blind, randomized trial of an oral analog of prostacyclin, known as beraprost, reduced the number of RP attacks but proved no more beneficial than placebo.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| oral treprostinil | Active comparator | Drug: oral treprostinil, Drug: PlaceboDosing of oral treprostinil will be initiated at 0.125 mg three times daily. Dose escalations of oral treprostinil can occur every 72 hours (three consecutive doses) in 0.125 mg increments. Subjects will be titrated as tolerated to a goal dose of 2mg TID over a 6-week period. |
| Placebo | Placebo comparator | Drug: oral treprostinil, Drug: PlaceboPlacebo mimics oral treprostinil and will be taken three times a day |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Patients aged ≥18-65 years
- Active Raynaud's Phenomenon defined as patients with refractory RP having four or more RP attacks per week in the 2 weeks before inclusion in the study despite treatment with vasodilators for at least 3 months
- Patients with primary Raynaud's Phenomenon
- Patients with Raynaud's secondary to connective tissue diseases (including scleroderma (SSc), limited scleroderma (CREST), mixed connective tissue disease (MCTD), primary Sjogren's syndrome (SS), systemic lupus erythematosus (SLE), with diagnosis of the underlying rheumatic disease based on standard criteria
- Patients on stable dose phosphodiesterase inhibitors (sildenafil, tadalafil or vardenafil), endothelin antagonists, alpha adrenergic antagonists, or calcium channel blockers defined as 3-months with no change in dose will be allowed to participate
Key exclusion criteria (5 listed)
- Uncontrolled hypertension, diabetes mellitus, history of orthostatic hypotension, acute coronary or cerebrovascular event within 3 months, evidence of malignancy, history of sympathectomy
- Smoking within 3 months or smoking cessation using nicotine products
- Subjects currently taking or other prostacyclins.
- Pregnant or breast feeding or considering pregnancy in next 4 months
- Participation in trial with an investigational drug within 30 days
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 |
|---|---|---|
| oral treprostinilAlso: OrenitramChange in the Raynaud's Condition Score from baseline (2-week run in), comparing treprostinil treatment phase vs. placebo phase | Drug | Placebo, oral treprostinil |
| PlaceboAlso: Sugar pillPlacebo is a sugar pill manufactured to resemble UT-15C. Change in the Raynaud's Condition Score from baseline (2-week run in), comparing treprostinil treatment phase vs. placebo phase | Drug | Placebo, oral treprostinil |
Primary outcome
Change in Raynaud's Condition Score
Time frame: from baseline (2-week run in) to 6 weeks of treatment
Change in the Raynaud's Condition Score from baseline (2-week run in), comparing treprostinil treatment phase vs. placebo phase
3 secondary outcomes
Change in number of Raynaud's Phenomenon attacks
Time frame: from baseline (2-week run in) to 6 weeks of treatment
Change in duration of Raynaud's Phenomenon attacks
Time frame: from baseline (2-week run in) to 6 weeks of treatment
Reduction of ulcer burden among secondary Raynaud's Phenomenon patients
Time frame: from baseline (2-week run in) to 6 weeks of treatment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jan 2022.
- Background: PubMed 26914257Ennis H, Hughes M, Anderson ME, Wilkinson J, Herrick AL. Calcium channel blockers for primary Raynaud's phenomenon. Cochrane Database Syst Rev. 2016 Feb 25;2(2):CD002069. doi: 10.1002/14651858.CD002069.pub5.
- Background: PubMed 22453196Roustit M, Hellmann M, Cracowski C, Blaise S, Cracowski JL. Sildenafil increases digital skin blood flow during all phases of local cooling in primary Raynaud's phenomenon. Clin Pharmacol Ther. 2012 May;91(5):813-9. doi: 10.1038/clpt.2011.302. Epub 2012 Mar 28.
- Background: PubMed 8923366Vayssairat M. Controlled multicenter double blind trial of an oral analog of prostacyclin in the treatment of primary Raynaud's phenomenon. French Microcirculation Society Multicentre Group for the Study of Vascular Acrosyndromes. J Rheumatol. 1996 Nov;23(11):1917-20.
- Individual participant dataSharing planned: No
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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.
Aaron Waxman, MD/PhD principal investigator
Brigham and Womens Hospital
Paul Dellaripa, MD principal investigator
Brigham and Womens Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing oral treprostinil in people with Raynaud's Phenomenon, run by Brigham and Women's Hospital at 1 site 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 5 inclusion and 5 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: finished, as of the sponsor's last update on 10 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Change in Raynaud's Condition Score (time frame: from baseline (2-week run in) to 6 weeks of treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02583789, which also lists 3 linked publications.
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 10 Jan 2022.