title: Efficacy of Rho kinase inhibitor fasudil in secondary Raynaud's phenomenon.
abstract: OBJECTIVE
  The RhoA/Rho kinase pathway plays a pivotal role in cold-induced vasoconstriction, vascular smooth muscle cells function, and vascular homeostasis. This study evaluates the efficacy of fasudil, a RhoA/Rho kinase inhibitor, to reverse cold-induced vasospasm in patients with Raynaud's phenomenon (RP) secondary to systemic sclerosis (SSc; scleroderma).
  
  
  METHODS
  This is a single-center, double-blind, placebo-controlled, randomized, 3-period crossover study of oral fasudil (40 mg or 80 mg) or placebo administered 2 hours before a standardized cold challenge. The fall in skin temperature after the cold challenge and time to recover 50% and 70% of prechallenge digital skin temperature were used as primary outcomes. Digital blood flow assessed by laser Doppler, time to minimum skin temperature, and rate of skin cooling were also measured.
  
  
  RESULTS
  A total of 17 patients with SSc and RP completed the study. After the cold challenge, skin temperatures and the average time (minutes) to recover 50% (7.9 minutes for placebo, 7.5 minutes for fasudil 40 mg, and 8.2 minutes for fasudil 80 mg; P = 0.791) and 70% (18.2 minutes for placebo, 15.0 minutes for fasudil 40 mg, and 17.1 minutes for fasudil 80 mg; P = 0.654) of prechallenge skin temperature were not significantly different across the 3 groups. The digital blood flow measurements were higher in fasudil-treated groups than placebo, but differences were not significant (P = 0.693).
  
  
  CONCLUSIONS
  Fasudil administered at a single oral dose of 40 mg or 80 mg was not associated with significant benefit in terms of the skin temperature recovery time and the digital blood flow after the cold challenge.
authors.affiliation: Division of Rheumatology, JohnsHopkins University School of Medicine, 5200 Eastern Avenue, Baltimore, MD 21224, USA.
authors.forename: Andrea
authors.initials: A
authors.lastname: Fava
authors.forename: Peter K
authors.initials: PK
authors.lastname: Wung
authors.forename: Fredrick M
authors.initials: FM
authors.lastname: Wigley
authors.forename: Laura K
authors.initials: LK
authors.lastname: Hummers
authors.forename: Natalie R
authors.initials: NR
authors.lastname: Daya
authors.forename: Sharon R
authors.initials: SR
authors.lastname: Ghazarian
authors.forename: Francesco
authors.initials: F
authors.lastname: Boin
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011928:Raynaud Disease / Q000188:drug therapy* / Q000209:etiology*; D012039:Regional Blood Flow / Q000187:drug effects; D012595:Scleroderma, Systemic / Q000150:complications*; D012867:Skin / Q000098:blood supply; D012881:Skin Temperature / Q000187:drug effects; D016896:Treatment Outcome; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors*
chemical_list: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D054460:rho-Associated Kinases; C049347:fasudil