A Two-Part Study of BOTOX® Therapy for Ischemic Digits
Condition: Raynaud's Disease
MeSH terms: Raynaud Disease
Study type: Interventional
Phase: Phase 2

Summary: 
      Treating patients with Raynaud's phenomenon who have chronic pain and ulcerations is
      extremely challenging. Published reports and our previous work support our hypothesis that
      symptomatic patients experience relief of pain and healing of ulcerations with minimal
      adverse effects when treated with botulinum toxin type A (Btx-A) injections for Raynaud's
      phenomenon. The proposed study is the first clinical trial and prospective study designed to
      document whether or not 1) Btx-A injection relieves pain in a patient's hand affected with
      Raynaud's disease better than a placebo within 28 days of injection, and 2) Btx-A injection
      relieves pain associated with Raynaud's disease for longer than 28 days, improving patients'
      quality of life. Through this study we intend to further determine the effect 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.
    

Detailed description: 
      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.
    

Intervention name(s): onabotulinum toxin type-A
Intervention type(s): Drug
Intervention description(s): up to 4 injections per hand dosage per injection: 100 units diluted in 2.0 mL normal saline; dosing will not exceed 360 units in a 3 month interval frequency: no less than 28 days between injections duration: during Study Year 1
Other intervention name(s): BOTOX®; botulinum toxin type A
Intervention MeSH terms: Botulinum Toxins; Botulinum Toxins, Type A; abobotulinumtoxinA
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary purpose: Treatment
Keywords: botox; raynaud's; botulinum toxin; botulinum toxin A; raynaud's disease; raynaud's syndrome; raynaud's phenomenon; ischemic digits; ischemia; botox treatment; onabotulinum; onabotulinum toxin; onabotulinum toxin type A