Treatment of Frostbite Sequelae With Botulinum Toxin A
NCT Number: NCT06460194
Status: WITHDRAWN
Study Type: INTERVENTIONAL
Phases: PHASE2
Conditions: Cold Hypersensitivity|Vascular System Injuries|Vibration; Disorder|Sensory Disorders|Pain, Nerve
Interventions: DRUG: Botuinum toxin
Sponsor: University Hospital of North Norway
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 0
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: DOUBLE (PARTICIPANT, INVESTIGATOR)|Primary Purpose: TREATMENT
Start Date: 2022-11
Completion Date: 2024-06-10
Locations: University Hospital of North Norway, Tromsø, 9038, Norway

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.

Primary Outcome Measures: Subjective symptoms between injection of Botox and placebo at 6 weeks follow up, 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., 6 weeks|Rewarming before and 6 weeks after treatment with Botulinum toxin, 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)., 6 weeks