As patients with scleroderma and Raynaud’s phenomenon know, cold hands can be extremely bothersome and even painful. Fredrick M. Wigley, MD, of Johns Hopkins University led a phase 3 clinical trial in 2014 that evaluated Fasudil, a Rho-kinase inhibitor, for efficacy in preventing vasoconstriction in the fingers and skin, an event that shuts off blood flow and reduces skin temperature. Results of treatment appear to be inconclusive.
“A Rho-kinase Inhibitor (Fasudil) in the Treatment of Raynaud’s Phenomenon” was completed by enrolling 17 patients, all of whom had a diagnosis of scleroderma with definite Raynaud’s phenomenon. During the trial, patients were split into six groups, and each group completed three periods during the trial. These three periods gave patients 80 mg Fasudil, 40 mg Fasudil, or a placebo. The timing and sequence of each treatment period was determined by the group, with all groups going through each treatment. Patients were given at least 24 hours between treatments, but no more than seven days.
During the specified period, patients took their dose of Fasudil or placebo orally two hours before undergoing a standardized cold challenge. The times for patients to recover 50% and 70% of the fall from baseline skin temperature were recorded after each cold challenge. Additionally, blood flow using Laser Doppler scans of the fingers served as secondary outcome measures.
No statistics were conducted on the results, making the data inconclusive. It was shown Fasudil 80 mg allowed 70% recovery within an average of 17.1 minutes, Fasudil 40 mg in 15.0 minutes, and placebo in 18.2 minutes. For 50% recovery, the times were 7.5 minutes, 8.2 minutes, and 7.9 minutes for Fasudil 40 and 80 mg and placebo, respectively. Finally, finger perfusion showed 138.3 perfusion units in the 80 mg Fasudil group and 134.1 perfusion units in the 40 mg Fasudil group, compared to 122.6 perfusion units in the placebo group.
Seemingly, Fasudil had no effect on the outcome of cold challenges. However, this could be due to a low sample size and large variability within treatment groups. No serious or adverse effects were experienced by any of the patients during the trial.
Fasudil blocks vasconstriction. In Raynaud’s phenomenon, the digital arteries and cutaneous arterioles are vasospastic, leading to skin color changes and ischemia as a result of vasoconstriction. Patients with Raynaud’s phenomenon are advised to avoid cold temperatures and emotional stress in order to improve their symptoms, but sometimes this is not enough. Since RhoA/Rho kinase are activated upon cooling and mediate vasoconstriction of cutaneous arteries, “RhoA/Rho kinase inhibition may provide a highly selective intervention directed toward the mechanisms underlying thermosensitive vasomotor responses in the skin of Raynaud’s phenomenon patients,” wrote Dr. Wigley.