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

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

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.

Study Overview

• Status: Completed
• Conditions: Chronic Pain; Lower Extremity Wound
• Intervention / Treatment: Drug: Botulinum Toxin A

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 4

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen, Denmark
    • Department of Dermatology and Copenhagen Wound Healing Center, Bispebjerg Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Botulinum Toxin A; Open-label study	Drug: Botulinum 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.

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Wound status- Degree of inflammation, granulation tissue, necrosis/slough, exudation and infection.	Semi-quantitatively measured (Absent/Low < 25 %, Mild 25-50 %, Moderate 51-75 %, High > 75%)	Throughout the trial (12-15 weeks)

Collaborators and Investigators

• Sponsor: Bispebjerg Hospital
• Investigators: Study Director: Simon Francis Thomsen, Professor, Department of Dermatology and Copenhagen Wound Healing Center, Bispebjerg Hospital

Study record dates

Study Major Dates

• Study Start (Actual): February 7, 2023
• Primary Completion (Actual): April 23, 2024
• Study Completion (Actual): April 23, 2024

Study Registration Dates

• First Submitted: June 14, 2022
• First Submitted That Met QC Criteria: June 16, 2022
• First Posted (Actual): June 21, 2022

Study Record Updates

• Last Update Posted (Actual): August 9, 2024
• Last Update Submitted That Met QC Criteria: August 7, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: Botulinum toxin A
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Chronic Pain; Wounds and Injuries; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Cholinergic Agents; Membrane Transport Modulators; Acetylcholine Release Inhibitors; Neuromuscular Agents; Botulinum Toxins; Botulinum Toxins, Type A; abobotulinumtoxinA
• Other Study ID Numbers: Botox-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No