Diabetic Peripheral Neuropathy, Painful Diabetic Neuropathy, Diabetic Foot Pain, Neuralgia
Conditions
Keywords
Botulinum Toxin Type A, Duloxetine, Perineural Injection, Ultrasound-guided Injection, Nerve Conduction Study, Foot Pain
Brief summary
Painful diabetic peripheral neuropathy (DPN) is a frequent and disabling complication of diabetes that commonly causes persistent foot pain, sleep impairment, and decreased quality of life. While oral medications such as duloxetine are established treatment options, many patients experience incomplete pain control or encounter dose-limiting side effects. Perineural botulinum toxin type A (BTX-A) injection has emerged as an interventional approach designed to inhibit peripheral pain signaling with targeted, prolonged local effect. The purpose of this study is to compare the efficacy and safety of a single session of ultrasound-guided perineural BTX-A injection versus standard daily oral duloxetine therapy in relieving foot pain in patients with painful diabetic peripheral neuropathy. Participants will be randomly assigned to one of two groups using a double-dummy design to preserve blinding: * Group B (Botulinum Toxin): Receives a single session of ultrasound-guided perineural botulinum toxin type A injection around the ankle nerves plus daily oral placebo tablets for 12 weeks. * Group D (Duloxetine): Receives a single session of sham subcutaneous injection plus oral duloxetine tablets daily for 12 weeks (30 mg once daily for week 1, increased to 60 mg once daily for weeks 2-12). Participants will be followed for 6 months to evaluate changes in foot pain intensity on the Visual Analogue Scale (VAS) at 1 week, 1 month, 3 months, and 6 months. The study will also assess objective peripheral nerve function through bilateral nerve conduction studies (NCS) at baseline and 6 months, alongside evaluations of neuropathic pain scores, sleep quality, quality of life, and adverse effects.
Interventions
DRUGBotulinum Toxin Type A
A single session of ultrasound-guided perineural injection of botulinum toxin type A (total dose 100 units reconstituted in 5 mL preservative-free 0.9% normal saline) administered around the ankle nerves (posterior tibial, superficial peroneal, deep peroneal, sural, and saphenous nerves) of the affected lower limb.
DRUGDuloxetine
Oral duloxetine administered once daily for a total of 12 weeks: initiated at 30 mg once daily for the first week (Week 1), then escalated to 60 mg once daily for the remaining 11 weeks (Weeks 2-12).
OTHEROral Placebo Tablet
Matching inert oral placebo tablets identical in appearance, packaging, and dosing schedule to duloxetine, taken once daily for 12 weeks.
OTHERSham Perineural Injection
Single-session ultrasound-guided superficial subcutaneous injection of 5 mL 0.9% sterile saline without perineural deposition around the ankle nerves to preserve participant masking.
Sponsors
Assiut University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
30 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Confirmed diagnosis of diabetes mellitus. * Clinically diagnosed painful diabetic peripheral neuropathy of the foot (Douleur Neuropathique en 4 questions \[DN4\] score ≥ 4) confirmed electrophysiologically by nerve conduction study. * Baseline foot pain Visual Analogue Scale (VAS) score ≥ 4 despite receiving non-SNRI first-line oral therapy (e.g., a gabapentinoid) for at least 4 weeks. * Duloxetine-naïve at the time of enrollment.
Exclusion criteria
* Peripheral neuropathy attributable to causes other than diabetes (e.g., vitamin B12 deficiency, hypothyroidism, alcohol-related, uremic, hereditary, or chemotherapy-induced neuropathy). * Known hypersensitivity to botulinum toxin, duloxetine, or other serotonin-norepinephrine reuptake inhibitors (SNRIs). * Local skin infection, active ulceration, or severe peripheral vascular disease at the intended injection site. * Coagulopathy or current anticoagulant/antiplatelet therapy that cannot be safely interrupted. * Pre-existing neuromuscular junction disorders (e.g., myasthenia gravis, Lambert-Eaton syndrome). * Current or recent (within 14 days) use of monoamine oxidase inhibitors (MAOIs), or concurrent use of other serotonergic agents. * Significant hepatic impairment, uncontrolled narrow-angle glaucoma, or uncontrolled hypertension. * Pregnancy or lactation. * Poorly controlled psychiatric illness or cognitive impairment precluding reliable reporting of pain and outcome measures.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from Baseline in Foot Pain Intensity on the Visual Analogue Scale (VAS) at 6 Months | Baseline and 6 months post-intervention | Foot pain intensity is assessed using the Visual Analogue Scale (VAS), an 11-point scale ranging from 0 (no pain) to 10 (worst imaginable pain). The score is calculated as the change from pre-intervention baseline to the 6-month follow-up visit. A negative change indicates pain reduction (clinical improvement). |
Outcome results
None listed