A double-blind, randomized, placebo-controlled crossover trial of the α2c-adrenoceptor antagonist orm-12741 for prevention of cold-induced vasospasm in patients with systemic sclerosis

Ariane L. Herrick, Andrea K. Murray, Angela Ruck, Juha Rouru, Tonia L. Moore, John Whiteside, Pasi Hakulinen, Fredrick Wigley, Amir Snapir

Research output: Contribution to journalArticlepeer-review


Objectives: Our primary purpose was to evaluate the efficacy of the high-potency α2C-adrenoceptor antagonist ORM-12741 in the attenuation of a cold-induced reduction in finger blood flow and temperature in patients with RP secondary to SSc. Secondary objectives were to assess safety and tolerability.Methods: This was a phase IIa, randomized, double-blind, crossover, single-dose, placebo-controlled, single-centre study. Patients attended five times: initial screening, treatment visits 1-3 (each at least 1 week apart) and 1-2 weeks after the last treatment. At each treatment visit, each subject received a single oral dose of 30 mg or 100 mg of ORM-12741 or placebo. Thirty minutes later the subject underwent a cold challenge. Blood flow to the fingers was assessed by three methods [temperature by probe, laser Doppler imaging (LDI) and infrared thermography] performed before, during and after the cold challenge.Results: Twelve patients (10 female, mean age 58 years) were included. The area under the rewarming curve (LDI) of the right index finger (arbitrary flux units × time) was lower for both 30 mg (P = 0.043) and 100 mg (P = 0.025) of ORM-12741 compared with placebo, indicating delayed reperfusion. The time to 70% temperature recovery (middle finger probe) was longer with active than placebo treatment: mean (s.d.) values for placebo, 30 mg of ORM-12741 and 100 mg of ORM-12741 were 21.4 min (12.4), 25.7 min (12.2) and 26.9 min (13.9), respectively. Overall ORM-12741 was well tolerated.Conclusion: ORM-12741 did not expedite recovery from a cold challenge in the fingers of patients with SSc.

Original languageEnglish (US)
Article numberket421
Pages (from-to)948-952
Number of pages5
JournalRheumatology (United Kingdom)
Issue number5
StatePublished - May 2014


  • Randomized controlled trial
  • Raynaud's phenomenon
  • Systemic sclerosis
  • α2C-adrenoceptor antagonism

ASJC Scopus subject areas

  • Rheumatology
  • Pharmacology (medical)


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