Randomized Comparative Study of Perineural Botulinum Toxin Injection Versus Oral Duloxetine in Relief of Foot Pain in Painful Peripheral Diabetic Neuropathy
| Registry | NCT07882238 |
|---|---|
| Status | Not yet recruiting |
| Phase | Phase 2 |
| Study type | Interventional; randomized, parallel, masking: double, treatment |
| Enrollment | 56 (Estimated) |
| Sponsor | Assiut University (Other) |
| Conditions | Diabetic Peripheral Neuropathy, Painful Diabetic Neuropathy, Diabetic Foot Pain, Neuralgia |
| Interventions | Botulinum Toxin Type A, Duloxetine, Oral Placebo Tablet, Sham Perineural Injection (Drug, other) |
| Dates | start 2026-11-01 (estimated), primary completion 2027-11-01 (estimated), completion 2027-12-01 (estimated), first posted 2026-10-20, last updated 2026-10-20 |
Related Papers Related Patents Related Grants Related Experts
All trials for Diabetic Peripheral Neuropathy All trials for Painful Diabetic Neuropathy All trials of Botulinum Toxin Type A All trials of Duloxetine
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.
| Arm | Type | Interventions | Description |
|---|---|---|---|
| Group B: Perineural Botulinum Toxin Type A | Experimental | Drug: Botulinum Toxin Type A; Other: Oral Placebo Tablet | Participants receive a single session of ultrasound-guided perineural injection of botulinum toxin type A (total dose 100 units reconstituted in 5 mL of preservative-free 0.9% saline) distributed around ankle nerves (posterior tibial, superficial peroneal, deep peroneal, sural, and saphenous nerves) of the affected lower limb. In addition, participants receive matching oral placebo tablets identical in appearance to duloxetine, taken once daily for 12 weeks (double-dummy design). |
| Group D: Oral Duloxetine | Active comparator | Drug: Duloxetine; Other: Sham Perineural Injection | Participants receive a single session of ultrasound-guided sham perineural injection (subcutaneous 0.9% saline without perineural deposition) to the affected lower limb. In addition, participants take active oral duloxetine: 30 mg once daily for the first week, escalated to 60 mg once daily for the subsequent 11 weeks (12 weeks total course; double-dummy design). |
Sex: All, ages: 30 Years to 70 Years
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.