Botulinum Toxin A in the treatment of frostbite sequelae – results from a blinded, early-phase, comparative trial

Abstract

Introduction: Freezing Cold Injuries (FCI) have been associated with long-term sequelae including vasospasm. The aims of the pilot study are to explore the research methodology and investigate the tolerability and safety of treatment with Botulinum Toxin-A (BTX-A) in FCI Sequelae. Methodology: This pilot study tests the logistics, the treatment setting and the follow-up procedure in an early-phase, double-blinded, randomized, controlled trial study-design. The variables in the study were subjective symptoms, peripheral micro-vascularization/rewarming, somatosensory responsiveness, and generic measure of health status. Results: No major challenges or difficulties were noticed according to the protocol or the study methodology. The monitoring of tolerability and safety of treatment with BTX-A did not reveal any major unwanted and/or adverse reactions among the patients in the pilot study and no challenges occurred during data collection of endpoints. The study revealed an inaccuracy of the 2nd degree FCI diagnosis and uncover a need for relevant and sufficient clinical information for FCI classification. Conclusions: This pilot study showed the study methodology with minor adjustments is feasible in a future full-scale clinical trial. The recruitment process needs to be more refined to ensure that the eligible study participants are a homogenous group of FCI patients.

Freezing cold injuries among soldiers in the Norwegian Armed Forces – A cross sectional study

“…Additionally, questions from a previous frostbite study were used. The questionnaire also include other instruments such as the European Quality of Life Scale (EuroQol) with five dimensions of health status to quantify health-related quality of life (EQ-5D) [ 21 ] and Patient Subjective Symptom Score (PSSS) to describe the most important subjective symptoms following a primary frostbite; pain, hypersensitivity to cold, numbness of fingers and declined sensitivity of touch [ 11 ] ( Table 2 ). The questionnaire consisted of multiple-choice questions leading to a higher number of answers than the total number of participants in some cases.…”

“…The treatment options for FCI are limited; these are often regarded as experimental or characterised as off-label treatment [ 11 , 12 ]. Since no evidence-based therapy is available, prevention plays an important role in FCI.…”

Human performance and medical treatment during cold weather operations – synthesis of a symposium

“…Norheim and colleagues [ 39 ] presented evidence from a case study, whereby off-label use of Botulinum Toxin A (BTX-A) was used to treat a patient suffering from long-term sequelae of frostbite to his hands after a military exercise. Frostbite sequelae may include cold hypersensitivity, sensory loss, chronic pain, hyperhidrosis, growth plate disturbances and osteoarthritis, and paraesthesia.…”

“…Frostbite sequelae may include cold hypersensitivity, sensory loss, chronic pain, hyperhidrosis, growth plate disturbances and osteoarthritis, and paraesthesia. The authors proposed the design of a more controlled multi-centre study of the potential use of BTX-A in the treatment of frostbite sequelae [ 39 ].…”