Botulinum Toxin A in the Treatment of Frostbite Sequelae - a Randomized, Double Blind, Placebo-controlled Study

2018/1961(REK)

Background Digital vasospasm as part of frostbite sequelae is comparable to the vasospastic disorders found in Raynaud's phenomenon which has been successfully treated with Botulinum toxin type A injections in the palm of the hands. Aim of this pilot study To investigate the effect of Botulinum toxin type A for frostbite sequelae in the fingers. Hypothesis The null hypothesis which is that all study-subjects will have equal distribution of symptoms and measurements after treatment, regardless of injection with Botulinum toxin type A or placebo. Methodology A randomized, double-blind, placebo-controlled study design, The study population consists of four patients with frostbite sequelae. The patients are randomized to either treatment with Botulinum toxin type A or placebo Two patients in the primary treatment group will receive Botulinum toxin type A at their first injection at inclusion, while the two patients in the secondary treatment group will receive normal saline (placebo) as their first injection at inclusion. At 6 weeks follow up, the primary treatment group will receive their second injection of Botulinum toxin type A and the secondary treatment group now will receive their second injection, but this will be their first injection of Botulinum toxin type A. By using the described study-design, all participating soldiers will get treatment. However, the secondary treatment group will have a delayed onset of treatment with Botulinum toxin type A and serves as a control for the primary treatment group during the initial 6 weeks observation. Botulinum toxin A and placed will be injected near the neurovascular bundle at the A1 pulley in the palm of the hand using a total dosage 100 U per hand (concentration 50 U per ml), 8-12 U/ injection site. The effect of Botulinum toxin type A on subjective symptoms will be measured by Patients Subjective Symptom Score (PSSS) The effect of Botulinum toxin type A on peripheral microcirculation will be evaluated with dynamic infrared thermography (DIRT) of the dorsal side of the hands. Quantitative sensory testing will be used to evaluate the effect of Botulinum toxin type A on peripheral nerve function. Both DIRT and QST will be performed prior to the treatment with Botulinum toxin type A and placebo at the start of the pilot study, at 6 weeks as well as 6 weeks after the last injections. Statistical methods and data analysis will be performed according to the EMA guidelines for biostatistics. Statistical analysis will be performed according to the null hypothesis.

2022-11-01

2023-07-01

2024-06-10

Withdrawn

Early phase I

Inclusion Criteria:- Sequela following 2nd degree frostbite injury in the Norwegian Armed Forces * Entering the Norwegian Armed Forces Health Registry (NAFHR) between 01.01.2010-31.12.2014 * Still suffering from sequelae related to frostbite injury in their fingers at least four years after their initial frostbite * Have agreed on receiving a request to participate in the NAFHR quality assurance study. Exclusion Criteria:- Patients who do not return the signed informed consent form * Patients who cannot read Norwegian information or answer questions in the study * Patients who are unable to comply the examination and treatment procedures * Patients who are unable to travel to University Hospital North Norway in Tromsø for examination and treatment * Patients who have undergone/is undergoing surgical treatment of hands/fingers * Patients with known allergy/anaphylaxis in relation to the injection of BTX-A * Patients who have used/are using drugs that interact with BTX-A injection (anticoagulants) * Patients who are pregnant before start of the trial and/or during the trial

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2024-06-14