Clinical Trials Logo

Clinical Trial Summary

Raynaud's phenomenon is thought to occur when, in response to cold or emotional stress, there is closure of the digital arteries and cutaneous arterioles leading to the clinical finding of sharp demarcated digital pallor and cyanosis of the distal skin of the fingers and/or toes. Patients often continue to experience problems despite current available treatment. The investigators' study will investigate the use of a new vasodilator called Fasudil, a Rho-kinase inhibitor. The investigators' hypothesis is that Fasudil will prevent vasoconstriction of digital and cutaneous arteries during a standard laboratory based cold exposure and will therefore improve digital blood flow and skin temperature recovery time following cold challenge. These data will provide the rationale for a more elaborate clinical trials in real life situations.


Clinical Trial Description

Raynaud's phenomenon (RP) is a reversible vasospastic disorder of digital arteries and cutaneous arterioles characterized by typical skin color changes and tissue ischemia (1). Avoidance of common triggers such as cold temperatures and emotional stress often leads to improvement of symptoms. When such a strategy yields inadequate benefits, pharmacologic therapy is needed.

Cutaneous vasoconstriction occurs through a general sympathetic adrenergic response and through local mechanisms in response to cold. While under normal conditions, the vasomotor tone is regulated mainly by a.2A- adrenoreceptors (a.2A-AR) expressed on vascular smooth muscle cells (VSMC) (2); during cold exposure the normally "silent" a.2C-AR relocate from the Golgi complex to the cell surface, driving the cold-induced vasoconstrictive response (3). Interestingly, the reactivity to a.2-AR stimulation is highly increased in cutaneous arteries of patients with systemic sclerosis (SSc; scleroderma) (4), and block- age of a.2C-AR has shown to shorten the time to recover digital skin temperature after a cold challenge in patients with Raynaud's Phenomenon secondary to Scleroderma (5).

The RhoA/Rho kinase pathway is activated by cooling and mediates vasoconstriction of cutaneous arteries by inducing a.2C-AR relocation to the cell surface and by increasing calcium-dependent Vascular Smooth Muscle Cells (VSMC )contractility (6). Rho kinase inhibition has been shown to effectively reduce

a.2-AR-mediated response during cold exposure and to prevent cold-induced vasoconstriction in human skin (6) Therefore, 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. ;


Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment


Related Conditions & MeSH terms


NCT number NCT00498615
Study type Interventional
Source Johns Hopkins University
Contact
Status Completed
Phase Phase 3
Start date April 2007
Completion date March 2012

See also
  Status Clinical Trial Phase
Completed NCT02798055 - Bosentan Treatment of Digital Ulcers Related to Systemic Sclerosis
Completed NCT01959815 - Novel Screening Strategies for Scleroderma PAH
Completed NCT03274076 - Evaluation of Tofacitinib in Early Diffuse Cutaneous Systemic Sclerosis (dcSSc) Phase 1/Phase 2
Completed NCT02915835 - Riociguat in Scleroderma Associated Digital Ulcers Phase 2
Active, not recruiting NCT01895244 - Autologous Stem Cell Transplantation for Progressive Systemic Sclerosis Phase 2
Completed NCT00883129 - Comparison of Therapeutic Regimens for Scleroderma Interstitial Lung Disease (The Scleroderma Lung Study II) Phase 2
Completed NCT00930683 - A Study to Evaluate Safety and Tolerability of Multiple Doses of MEDI-546 in Adult Subjects With Scleroderma Phase 1
Completed NCT00074568 - Scleroderma Registry
Recruiting NCT04797286 - Sildenafil for Early Pulmonary Vascular Disease in Scleroderma Phase 2
Completed NCT03222492 - Brentuximab Vedotin for Systemic Sclerosis Phase 1/Phase 2
Completed NCT03207997 - MRI Quantification of Pulmonary Fibrosis in Scleroderma Patients N/A
Recruiting NCT04464434 - Upfront Autologous HSCT Versus Immunosuppression in Early Diffuse Cutaneous Systemic Sclerosis Phase 4
Recruiting NCT04246528 - SPIN Self-Management Feasibility Trial With Progression to Full-scale Trial (SPIN-SELF) N/A
Completed NCT05080738 - Upper Extremity Home Exercises in Patients With Scleroderma N/A
Recruiting NCT03726398 - CompRehensive Phenotypic Characterization of Patients With Scleroderma-Associated ILD and PH Phase 2/Phase 3
Recruiting NCT05085444 - A Study of CD19/BCMA Chimeric Antigen Receptor T Cells Therapy for Patients With Refractory Scleroderma Early Phase 1
Completed NCT02062125 - Calcinosis in a Single-Center Scleroderma Population
Completed NCT04588714 - Feasibility and Preliminary Effects of the Resilience-based, Energy Management to Enhance Wellbeing in Systemic Sclerosis (RENEW) Intervention N/A
Recruiting NCT05635266 - Tissue Repository Providing Annotated Biospecimens for Approved Investigator-directed Biomedical Research Initiatives
Completed NCT02835196 - Optical Elastography of Systemic Sclerosis Skin