A Two-Part Study of BOTOX® Therapy for Ischemic Digits

• number of pain-free days [ Time Frame: change from baseline to 28 days ] [ Designated as safety issue: No ]
  Subjective pain scales [visual analogue scale (VAS) and faces pain assessment]
  
  

• quality of life [ Time Frame: change from baseline to 28 days ] [ Designated as safety issue: No ]
  SF-12v2® Health Survey - Pain Enhanced
  
  
• hand function [ Time Frame: change from baseline to 28 days ] [ Designated as safety issue: No ]
  Quick-DASH (Disabilities of the Arm, Shoulder, and Hand) Outcome Measure
  
  
• patient satisfaction [ Time Frame: change from baseline to 28 days ] [ Designated as safety issue: No ]
  SF-12v2® Health Survey - Pain Enhanced
  
  
• tissue perfusion [ Time Frame: change from baseline to 28 days ] [ Designated as safety issue: No ]
  Doppler perfusion imager and Periscan image analysis software
  
  
• quality-adjusted life-years [ Time Frame: change from baseline to 28 days ] [ Designated as safety issue: No ]
  EuroQol (EQ-5D)
  
  

PROJECT SUMMARY OVERVIEW: Treating patients with Raynaud's phenomenon who have chronic pain and ulcerations is extremely challenging. Pharmacologic vasodilators and surgical sympathectomies offer variable benefits. Case reports, small retrospective outcomes studies, and our previous work documenting symptomatic patients treated with botulinum toxin type A (Btx-A) injections for Raynaud's phenomenon have demonstrated relief of pain and healing of ulcerations with minimal adverse effects. We propose to conduct the first clinical trial and prospective study documenting the efficacy of this novel treatment modality.

STUDY AIMS: The aims of this proposal are to 1) examine the short-term efficacy of Btx-A injection compared to placebo in treating pain associated with digit ischemia due to Raynaud's disease, and 2) describe the long-term efficacy of Btx-A injection in treating pain associated with digit ischemia due to Raynaud's disease by measuring patient satisfaction and quality of life changes over time.

APPROACH: Two groups of patients will be enrolled: Group 1 will consist of patients with primary Raynaud's disease (n=20) and Group 2 of patients with secondary Raynaud's (n=20). Comparisons between treatment (Btx) and placebo (saline) will occur during the first 28 days to determine Btx-A's short-term efficacy. Follow-up visits will occur at Days 7 and 28. Post-assessment on Day 28 marks the beginning of the longitudinal observational study of patient outcomes. Placebo will no longer be used and patients still suffering from pain will be eligible for additional Btx-A injections. Patients may receive up to 4 injections of Btx-A during the 1-year study period if pain or ulcerations recur. During the study period participants will be followed to collect data on pain-free intervals, ulcer healing, subsequent treatment choices, patient satisfaction, and changes in quality of life and hand function. Group comparisons will be made to analyze results. Further stratifications for data analysis will be made as enrollment numbers allow to control for additional demographic and disease variables. Quality-adjusted life-years will be calculated to help determine the societal and individual cost of this treatment.

HYPOTHESIS: We hypothesize that 1) Btx-A injection relieves ischemic pain associated with Raynaud's disease better than a placebo within 28 days of injection, and 2) Btx-A injection relieves ischemic pain associated with Raynaud's disease for longer than 28 days, improving patients' quality of life. Through this study we intend to further elucidate the efficacy of injected Btx-A on relieving chronic pain and ulcerations to the ischemic hand while characterizing the patients for whom this treatment is most effective. This data will help us to apply for national funding to become the coordinating center for a multi-center clinical trial. The results of this research have enormous potential to impact millions of patients who suffer with Raynaud's phenomenon.