Botulinum Toxin A in the Treatment of Frostbite Sequelae - a Randomized, Double Blind, Placebo-controlled Study
Trial Snapshot
- Phase
- Phase 2
- Status
- Withdrawn
- Sponsor
- Locations
- 1
- Primary Endpoint
- Subjective symptoms between injection of Botox and placebo at 6 weeks follow up
Study Overview
Brief Summary
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.
Detailed Description
Background Frostbite sequelae can have a significant negative impact on quality of life. Depending on the type of frostbite, sequelae such as cold hypersensitivity, sensory loss, chronic pain, hyperhidrosis, growth plate disturbances and osteoarthritis may develop. Long-term paraesthesia with occasional electric shock-type sensations have also been repored. The pathophysiology of these sequelae is still poorly understood although peripheral neurovascular dysfunction plays an important role. This may result in a vasospastic disorder similar as in Raynaud's phenomenon.
Recently, the use of Botulinum toxin type A (BTX-A) for the treatment of vasospastic disorders of the hand has shown to result in great benefits for the patients by reducing the severity and number of vasospastic disorders. BTX-A injections are targeting the neurovascular bundle at or slightly proximal to the A1 pulley in the palm of the hand.
A case history has described the off-label use of BTX-A to treat a Norwegian soldier who suffered from long-term sequelae of frostbite to his hands after a military exercise. He was successfully treated with BTX-A injections in each palm of the hand. At follow up, the patient reported less pain, warmer hands and improved sensory function. Dynamic Infrared thermography (DIRT) showed improved rewarming of all fingers compared to the pre-treatment examination, while Quantattive sensory testing (QST) showed a normalization of sensory function.
Aim of this pilot study To investigate the effect of Botulinum toxin type A for frostbite sequelae in fingers.
Hypothesis The null hypothesis 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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Masking Description
double blind
Eligibility Criteria
- Ages
- 20 Years to 65 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
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
Arms & Interventions
Botulinum toxin
100 IU botulinum toxin injection in the palm of the hand
Intervention: Botuinum toxin (Drug)
Placebo
Saline injection in the palm of the hand
Intervention: Botuinum toxin (Drug)
Outcomes
Primary Outcomes
Subjective symptoms between injection of Botox and placebo at 6 weeks follow up
Time Frame: 6 weeks
According to clinical experience, the patient s experience improvement in subjective symptoms after 4-6 weeks follow-up. The patient's subjective symptoms are monitored in a questionnaire of neurological and vasoactive sensations by comparing Patient-Subjective-Symptom-Score (PSSS) wustionnaire after 6 weeks with the baseline values for each patient.
Rewarming before and 6 weeks after treatment with Botulinum toxin
Time Frame: 6 weeks
According to clinical experience, an improvement is found in the rewarming ability after 4-6 weeks follow-up after injection of Botox. The patients rewarming ability is monitored by comparing the results from Dynamic Infrared Thermography (DIRT) after 6 weeks with the baseline values for each patient. The DIRT examines the dynamic regulation of peripheral micro-vascularization. Examination of the dorsal side of the hands encompasses a pre-cooling phase (T1), a cooling phase with hands immersed in water for one minute (T2), and a four-minute recovery phase (T3, T4, T5 and T6).
Secondary Outcomes
No secondary outcomes reported