Botulinum Toxin Type A Versus Local Anesthetic Injection for Chronic Neuroma Pain After Combat-Related Amputation

Official title

Botulinum Toxin Type A Versus Local Anesthetic Injection for Chronic Neuroma Pain After Combat-Related Amputation: A Multicenter Randomized Double-Blind Trial

Overview

Patients with combat-related amputations frequently experience persistent neuroma pain that may interfere with rehabilitation, prosthesis use, sleep, mobility, and quality of life. Current treatment options often provide only temporary relief. This study aims to compare two ultrasound-guided injection approaches for chronic neuroma pain after combat-related amputation: botulinum toxin type A and local anesthetic injection. Participants will be randomly assigned to receive one of the two treatments. Pain intensity, neuropathic pain symptoms, phantom limb pain, prosthesis tolerance, and functional outcomes will be evaluated during follow-up visits over a 24-week period. The goal of the study is to determine whether botulinum toxin type A provides longer-lasting pain reduction and improved functional recovery compared with local anesthetic injection in patients with chronic neuroma pain after combat-related amputation.

Detailed description

Neuroma pain is a common and disabling complication after combat-related limb amputation. Persistent neuroma pain may contribute to residual limb pain, phantom limb pain, impaired prosthesis tolerance, sleep disturbance, reduced mobility, and decreased quality of life. Conventional treatment strategies, including local anesthetic injections, often provide only temporary pain relief.

Botulinum toxin type A has emerged as a potential treatment option because of its ability to modulate peripheral nociceptive signaling, reduce neurogenic inflammation, and decrease peripheral sensitization. However, evidence regarding its efficacy in patients with combat-related amputations remains limited.

The NEUROQUIET Trial is a multicenter, randomized, double-blind clinical trial designed to compare ultrasound-guided botulinum toxin type A injection versus ultrasound-guided local anesthetic injection for persistent neuroma pain after combat-related amputation.

Eligible participants with ultrasound-confirmed painful neuroma will be randomized in a 1:1 ratio to receive either botulinum toxin type A or local anesthetic injection under ultrasound guidance. Participants, outcome assessors, and data analysts will remain blinded to treatment allocation.

Patients will undergo longitudinal follow-up for 24 weeks. Outcomes will include pain intensity, neuropathic pain characteristics, phantom limb pain, residual limb pain, prosthesis tolerance, analgesic consumption, sleep disturbance, and patient-reported global improvement.

The study aims to determine whether botulinum toxin type A provides greater and longer-lasting analgesia compared with local anesthetic injection in patients with chronic neuroma pain following combat-related amputation.

Interventions

• Drug Botulinum Toxin Type A (BoNT-A)
  Ultrasound-guided perineuroma injection of botulinum toxin type A for treatment of persistent neuroma pain after combat-related amputation.
• Drug Local Anesthetic Solution
  Ultrasound-guided perineuroma injection of local anesthetic for treatment of persistent neuroma pain after combat-related amputation.

Primary outcome measures

• Change in neuroma pain intensity measured [Time frame: Baseline to 12 weeks after intervention]

Secondary outcome measures (6)

• Residual Limb Pain Intensity Assessed Using the Numeric Rating Scale (NRS) [Time frame: Baseline to 24 weeks]
• Pain Catastrophizing [Time frame: Baseline, 3 months, 6 months, and 12 months after amputation.]
• Prosthesis Tolerance Assessed Using the Prosthesis Evaluation Questionnaire (PEQ) - Utility and Satisfaction Domains [Time frame: Baseline to 24 weeks]
• Analgesic Consumption [Time frame: Baseline to 24 weeks]
• Patient Global Impression of Change (PGIC) [Time frame: Week 12 and Week 24]
• Adverse Events [Time frame: Baseline to 24 weeks]

Eligibility criteria

Inclusion criteria

• Age ≥18 years
• Combat-related limb amputation
• Persistent neuroma pain lasting ≥3 months
• Ultrasound-confirmed neuroma
• Positive Tinel sign over the neuroma
• Average pain intensity ≥4/10 on the Numeric Rating Scale (NRS)
• Stable analgesic regimen for at least 14 days before enrollment
• Ability to provide written informed consent

Exclusion criteria

• Active infection at the injection site
• Previous botulinum toxin injection within 6 months
• Previous neuroma surgery within 3 months
• Severe uncontrolled psychiatric disorder
• Coagulopathy or anticoagulant therapy contraindicating injection
• Known allergy to botulinum toxin or local anesthetics
• Severe uncontrolled systemic disease
• Inability to complete study follow-up or questionnaires

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Treatment

Study locations

Ukraine · 2 centers

• Feofaniya Clinical Hospital — Kyiv
• Vinnitsya university hospital — Vinnitsa

Publications

• Climent JM, Mondejar-Gomez F, Rodriguez-Ruiz C, Diaz-Llopis I, Gomez-Gallego D, Martin-Medina P. Treatment of Morton neuroma with botulinum toxin A: a pilot study. Clin Drug Investig. 2013 Jul;33(7):497-503. doi: 10.1007/s40261-013-0090-0. PMID 23740337

Identifiers

NCT: NCT07626983 · 2205v0123052026 · UARA-NEUROQUIET · UARA-NEUROQUIET

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗