TY - JOUR
T1 - Efficacy of Rho kinase inhibitor fasudil in secondary Raynaud's phenomenon
AU - Fava, Andrea
AU - Wung, Peter K.
AU - Wigley, Fredrick M.
AU - Hummers, Laura K.
AU - Daya, Natalie R.
AU - Ghazarian, Sharon R.
AU - Boin, Francesco
PY - 2012/6
Y1 - 2012/6
N2 - 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). Conclusion: 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.
AB - 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). Conclusion: 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.
UR - http://www.scopus.com/inward/record.url?scp=84863202226&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84863202226&partnerID=8YFLogxK
U2 - 10.1002/acr.21622
DO - 10.1002/acr.21622
M3 - Article
C2 - 22275160
AN - SCOPUS:84863202226
SN - 2151-464X
VL - 64
SP - 925
EP - 929
JO - Arthritis Care and Research
JF - Arthritis Care and Research
IS - 6
ER -