The Effect of Subcutaneous Injection of Botulinum Toxin A on Chronic Wound Pain in Lower Extremities

Study Overview
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Brief Summary
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The aim of the study is to investigate the effect of subcutaneous administration of Botulinum toxin A on wound pain, wound healing and safety of treatment.

Official Title
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The Effect of Subcutaneous Injection of Botulinum Toxin A on Chronic Wound Pain in Lower Extremities, a Prospective Exploratory Study

Conditions
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Chronic Pain, Lower Extremity Wound

Intervention / Treatment
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* Drug: Botulinum Toxin A


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years old. Lower extremity ulcer ≥ 4 weeks. Ulcer area ≥ 1,5 cm2 and ≤ 20 cm2 Patients with neuropathic pain related to the ulcer (daily VAS pain scores ≥ 30 mm at rest and DN4 score ≥ 4). Normal monofilament and vibration test in lower extremities. Patients who can fill out pain diary correctly. Written informed consent to participate in the study after having fully understood the contents of the protocol and restrictions. Exclusion Criteria: 1. Infection at injection site. 2. Hypersensitivity to botulinum toxin A. 3. Peripheral neuropathy. 3. Diabetic foot ulcer. 4. Unstable critic peripheral ischemia judged by investigator 5. Exposed capsule, tendon, muscle or bone in the ulcers. 6. Tunnelling, undermining or sinus tracts. 7. Disorders of the neuromuscular junction (e.g. Myasthenia). 8. Topical analgesic (e.g Biatain ibu or Lidocain) within 7 days before inclusion. 9. Pregnant or lactating woman and woman with childbearing potential but does not use contraception. 10. Judgment by the investigator that the patient is not suited for study participation.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: A single-center, prospective, exploratory study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Botulinum Toxin A<br>Open-label study | Drug: Botulinum Toxin A<br>* Botulinum Toxin A (10 units per cm2 wound areal) will be injected subcutaneously around the wound (1-2 cm from wound edge) maximum 200 units at each injection time.The total dose of BoNTA is maximum 400 units. Patient will receive one or two treatments in total.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients reaching a reduction in mean visual analog scale (VAS) > 20 mm (at rest) in dynamic pain scores at study day 21 or 41 | At study day 0 the mean VAS will be calculated at rest for D-2-0 and at D21 or D41 mean VAS will be calculated for D19-21 or D39-41 | 3 to 6 weeks after first injection of Botulinum toxin a | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute and percentage change in the area of hyperalgesia and allodynia | Area of hyperalgesia and allodynia will be assessed at D0, D21/41 and D90/110 | 3 to15 weeks after first injection of Botulinum toxin a. | 
| Absolute and percentage change of the ulcer area. | The ulcer size will be measured at every visit with study day 0 as baseline. | Throughout the trial (12-15 weeks) | 
| Clinical improvement of the wound healing process | Semi-quantitatively measured (major improvement, minor improvement, status quo or worsening) | Throughout the trial (12-15 weeks) | 
| Therapeutic doses of Botulinum toxin a to treat wound pain | Number of patients who need a second injection of Botulinum toxin a on study D21 if mean VAS (D19-21) are similar (± 10 %) to the pre-injection mean VAS at D0 | 3 and 6 weeks after first injection | 
| Incidence of Treatment-Emergent Adverse Events | All clinical adverse events will be assessed and recorded. | Throughout the trial (12-15 weeks) | 
| Exploratory measurement: Changes in the levels of cytokines and pain related substances in the wound fluid before and after injection with Botulinum toxin a | Changes in the levels of cytokine and pain related substances will be quantified over time (throughout the trial). Prospects to analyse i.g ( IL-6, NGF, IL-1β) with either MSD,Luminex or ELISA. The results will be expressed as pg/ mg. | Analysis within 1 year after study completion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Botulinum toxin A