Assess Efficacy of of Oral Treprostinil in Patients With Symptomatic Primary or Secondary Raynaud's Phenomenon
Condition: Raynaud's Phenomenon
MeSH terms: Raynaud Disease
Study type: Interventional
Phase: Early Phase 1

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. 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.
    

Intervention name(s): oral treprostinil; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Change in the Raynaud's Condition Score from baseline (2-week run in), comparing treprostinil treatment phase vs. placebo phase; 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
Other intervention name(s): Orenitram; Sugar pill
Intervention MeSH terms: Treprostinil
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment