Chronic Pain, Lower Extremity Wound
Conditions
Keywords
Botulinum toxin A
Brief summary
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.
Interventions
DRUGBotulinum Toxin A
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.
Sponsors
Bispebjerg Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
A single-center, prospective, exploratory study
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age ≥ 18 years old. 2. Lower extremity ulcer ≥ 4 weeks. 3. Ulcer area ≥ 1,5 cm2 and ≤ 20 cm2 4. Patients with neuropathic pain related to the ulcer (daily VAS pain scores ≥ 30 mm at rest and DN4 score ≥ 4). 5. Normal monofilament and vibration test in lower extremities. 6. Patients who can fill out pain diary correctly. 7. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 3 to 6 weeks after first injection of Botulinum toxin a | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Absolute and percentage change in the area of hyperalgesia and allodynia | 3 to15 weeks after first injection of Botulinum toxin a. | Area of hyperalgesia and allodynia will be assessed at D0, D21/41 and D90/110 |
| Absolute and percentage change of the ulcer area. | Throughout the trial (12-15 weeks) | The ulcer size will be measured at every visit with study day 0 as baseline. |
| Clinical improvement of the wound healing process | Throughout the trial (12-15 weeks) | Semi-quantitatively measured (major improvement, minor improvement, status quo or worsening) |
| Incidence of Treatment-Emergent Adverse Events | Throughout the trial (12-15 weeks) | All clinical adverse events will be assessed and recorded. |
| Exploratory measurement: Changes in the levels of cytokines and pain related substances in the wound fluid before and after injection with Botulinum toxin a | Analysis within 1 year after study completion | 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. |
| Therapeutic doses of Botulinum toxin a to treat wound pain | 3 and 6 weeks after first injection | 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 |
Other
| Measure | Time frame | Description |
|---|---|---|
| Wound status- Degree of inflammation, granulation tissue, necrosis/slough, exudation and infection. | Throughout the trial (12-15 weeks) | Semi-quantitatively measured (Absent/Low \< 25 %, Mild 25-50 %, Moderate 51-75 %, High \> 75%) |
Countries
Denmark
Outcome results
None listed