Chronic Pain Due to Injury, Combat Related Symptoms, Neural Injury, Neuroma of Lower Limb, Neuroma of Upper Limb
Conditions
Keywords
Neuroma pain, Combat-related amputation, Botulinum toxin type A, Local anesthetic injection, Ultrasound-guided injection, Phantom limb pain, Residual limb pain, Neuropathic pain, Military trauma, Chronic post-amputation pain, Ultrasound-guided pain intervention
Brief summary
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
Ultrasound-guided perineuroma injection of botulinum toxin type A for treatment of persistent neuroma pain after combat-related amputation.
Ultrasound-guided perineuroma injection of local anesthetic for treatment of persistent neuroma pain after combat-related amputation.
Sponsors
Ukrainian Society of Regional Anesthesia and Pain Therapy
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
Participants, investigators performing outcome assessment, and data analysts will remain blinded to treatment allocation throughout the study period. Study medications will be prepared in identical syringes to maintain masking.
Intervention model description
Participants will be randomized in a 1:1 ratio to receive either ultrasound-guided botulinum toxin type A injection or ultrasound-guided local anesthetic injection for persistent neuroma pain after combat-related amputation. The study will use a parallel-group design in which each participant receives only one assigned intervention throughout the study period. Participants, outcome assessors, and data analysts will remain blinded to treatment allocation.
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in neuroma pain intensity measured | Baseline to 12 weeks after intervention | Assessment of change in average neuroma pain intensity using an 11-point Numeric Rating Scale (0 = no pain, 10 = worst imaginable pain) following ultrasound-guided injection treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Residual Limb Pain Intensity Assessed Using the Numeric Rating Scale (NRS) | Baseline to 24 weeks | Residual limb pain intensity will be assessed using the 11-point Numeric Rating Scale (NRS). Participants will rate their average residual limb pain during the previous 7 days on a scale from 0 to 10, where 0 indicates "no pain" and 10 indicates "worst imaginable pain." Higher scores indicate greater pain intensity and a worse clinical outcome. Scale Information: Numeric Rating Scale (NRS) Minimum Value: 0 Maximum Value: 10 Interpretation: Higher scores indicate worse residual limb pain intensity. |
| Pain Catastrophizing | Baseline, 3 months, 6 months, and 12 months after amputation. | Pain catastrophizing will be assessed using the Pain Catastrophizing Scale (PCS), a validated 13-item self-report questionnaire designed to measure catastrophic thinking related to pain. The PCS evaluates three domains: rumination, magnification, and helplessness. Total scores range from 0 to 52, with higher scores indicating greater levels of pain catastrophizing and a worse psychological pain profile. Scale Information: Pain Catastrophizing Scale (PCS) Minimum Value: 0 Maximum Value: 52 Interpretation: Higher scores indicate greater pain catastrophizing and worse pain-related psychological outcomes. |
| Prosthesis Tolerance Assessed Using the Prosthesis Evaluation Questionnaire (PEQ) - Utility and Satisfaction Domains | Baseline to 24 weeks | Prosthesis tolerance will be assessed using selected domains of the Prosthesis Evaluation Questionnaire (PEQ), a validated instrument evaluating comfort, utility, satisfaction, and functional use of the prosthesis. Scores range from 0 to 100, with higher scores indicating better prosthesis tolerance and satisfaction. Scale Information: Prosthesis Evaluation Questionnaire (PEQ) Minimum Value: 0 Maximum Value: 100 Interpretation: Higher scores indicate better prosthesis tolerance, comfort, and prosthetic adaptation. |
| Analgesic Consumption | Baseline to 24 weeks | Analgesic consumption will be assessed by calculating the total daily analgesic use and converting opioid medications into Oral Morphine Equivalent Daily Dose (OMEDD). Non-opioid analgesics (e.g., acetaminophen, NSAIDs, gabapentinoids) will also be recorded. Higher opioid consumption indicates greater analgesic requirements and potentially more severe pain. Measurement: Oral Morphine Equivalent Daily Dose (OMEDD), expressed in milligrams per day (mg/day) Minimum Value: 0 mg/day Maximum Value: No predefined maximum value Interpretation: Higher values indicate greater analgesic consumption and higher pain management requirements. |
| Patient Global Impression of Change (PGIC) | Week 12 and Week 24 | Overall perceived improvement will be assessed using the Patient Global Impression of Change (PGIC) scale. The PGIC is a validated patient-reported outcome measure that evaluates a participant's perception of change in pain, function, and overall health status since the beginning of treatment. Participants rate their overall improvement on a 7-point scale ranging from "Very much worse" to "Very much improved." Scale Information: Patient Global Impression of Change (PGIC) Minimum Value: 1 (Very much worse) Maximum Value: 7 (Very much improved) Interpretation: Higher scores indicate greater perceived improvement and better overall clinical outcomes. Scale Categories: 1. = Very much worse 2. = Much worse 3. = Minimally worse 4. = No change 5. = Minimally improved 6. = Much improved 7. = Very much improved |
| Adverse Events | Baseline to 24 weeks | Adverse events will be assessed by recording the occurrence, type, severity, and relationship to treatment throughout the study period. Events may include medication-related adverse effects, prosthesis-related complications, falls, skin breakdown, residual limb complications, infections, hospitalizations, and other clinically significant events. Severity will be graded according to the Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0, when applicable. Measurement: Number of participants experiencing one or more adverse events. Minimum Value: 0 participants Maximum Value: Number of participants enrolled in the study Interpretation: Higher values indicate a greater incidence of adverse events and worse safety outcomes. Additional Safety Assessment: Severity of adverse events will be categorized as Grade 1 (Mild) to Grade 5 (Death related to adverse event) according to CTCAE v5.0. |
Countries
Ukraine
Contacts
CONTACTDmytro Dmytriiev, PhD.Professor
Outcome results
None listed