A 28-Day Prospective, Randomized, Double-Blind, Placebo Controlled Clinical Trial Of Botulinum Toxin Type A For Raynaud's Phenomenon

Objective: Since Raynaud’s phenomenon affects an estimated 28 million Americans, causing ischemia, severe pain, and nonhealing ulcers, our objectives are to examine the short- and long-term effectiveness of Botulinum Toxin Type A (Btx-A) injections in treating digit ischemia and pain due to Raynaud’s disease/phenomenon.

Methods: A prospective, randomized, placebo-controlled clinical trial describes the efficacy of injected Btx-A in alleviating pain due to Raynaud’s disease. We will also describe this minimally invasive therapy’s effects and impact on quality-of-life by measuring subjective pain scores, pain-free intervals, ulcer healing, changes in hand function, finger survival, and subsequent treatment choices. Study participants were randomized to receive injection with either placebo (normal saline) or up to 100 units of Btx-A into the palmar digital neurovascular bundles. Data collection included subjective evaluation of pain relief, serial photography of wound healing, and objective data on tissue perfusion using a Doppler perfusion imager and Periscan image analysis software.

Results: Currently, 35 patients, including 20 primary and 15 secondary Raynaud's patients, are actively participating in the study, which represents 88% of our total enrollment target (n=40). Seventeen of these subjects received placebo at the first study visit, and eighteen received the study agent, Btx-A. At presentation, twenty-three patients reported pain as their primary complaint. At one month, one out of ten (10%) placebo patients compared with eight out of thirteen (62%) Btx-A patients reported pain relief (p=.0288). At this follow-up visit, patients were unblinded, and placebo patients were offered Btx-A injections. Similarly, a follow up survey with average duration of 239 days post-Btx-A injection showed 22 of 35 patients (63%) reported symptom relief after injection with Btx-A. Average duration of symptom relief was 127 days. Six of ten patients (60%) with fingertip ulceration healed after Btx-A injection.

Conclusions: Btx-A injection may be an effective, localized, nonsurgical treatment option without addictive properties or systemic side effects for treatment of ischemic digits. Preliminary results show a statistically significant number of Raynaud’s patients injected with Btx-A report pain relief compared with placebo at 1 month follow-up, and 60% of patients with fingertip ulcerations healed their wounds.  The second part of this study is to follow these patients for 5 years to determine the long-term efficacy of Btx-A injection for Raynaud’s phenomenon.