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

Rheumatology (Oxford). 2014 May;53(5):948-52. doi: 10.1093/rheumatology/ket421. Epub 2014 Jan 31.


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.

Trial registration: https://www.clinicaltrialsregister.eu/; no. 2010-024005-13.

Keywords: Raynaud’s phenomenon; randomized controlled trial; systemic sclerosis; α2C-adrenoceptor antagonism.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic alpha-2 Receptor Antagonists / adverse effects
  • Adrenergic alpha-2 Receptor Antagonists / pharmacology*
  • Adrenergic alpha-2 Receptor Antagonists / therapeutic use*
  • Adult
  • Aged
  • Benzofurans / adverse effects
  • Benzofurans / pharmacology
  • Benzofurans / therapeutic use
  • Body Temperature / drug effects
  • Body Temperature / physiology
  • Cold Temperature / adverse effects*
  • Cross-Over Studies
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Epinephrine / blood
  • Female
  • Fingers / blood supply
  • Humans
  • Laser-Doppler Flowmetry
  • Male
  • Middle Aged
  • Norepinephrine / blood
  • Quinolizidines / adverse effects
  • Quinolizidines / pharmacology
  • Quinolizidines / therapeutic use
  • Raynaud Disease / etiology*
  • Raynaud Disease / physiopathology
  • Raynaud Disease / prevention & control*
  • Receptors, Adrenergic, alpha-2 / drug effects*
  • Regional Blood Flow / drug effects
  • Regional Blood Flow / physiology
  • Scleroderma, Systemic / complications*
  • Thermography
  • Treatment Outcome


  • Adrenergic alpha-2 Receptor Antagonists
  • Benzofurans
  • ORM-12741
  • Quinolizidines
  • Receptors, Adrenergic, alpha-2
  • Norepinephrine
  • Epinephrine