NCT07440173

Phenol and Botulinum Toxin vs Botulinum Toxin Alone for Post-Stroke Upper-Limb Spasticity

Combined Phenol and Botulinum Toxin vs Botulinum Toxin Alone for Upper-Limb Spasticity After Stroke: A Randomized Trial

• Status: Not Yet Recruiting
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 60 (estimated)
• Sponsor: Assiut University · Academic / Other
• Sex: All
• Age: 18 Years – 70 Years
• Healthy volunteers: Not accepted

Summary

This study aims to evaluate the efficacy of a combined treatment approach for post-stroke upper limb spasticity using phenol neurolysis and botulinum toxin (BoNT). Spasticity is a common post-stroke complication that leads to muscle stiffness and significantly hinders functional recovery. While botulinum toxin is the standard treatment, its high cost often limits its application, particularly for large proximal muscles. The researchers will compare two treatment strategies in 60 adult stroke survivors: Group A (Combined Therapy): Patients will receive ultrasound-guided phenol neurolysis for the proximal nerves (pectoralis and musculocutaneous nerves) and botulinum toxin for the distal forearm flexors. Group B (Standard Care): Patients will receive botulinum toxin alone for all affected muscles in the upper limb. All procedures will be performed under ultrasound guidance to ensure anatomical precision. The study will also utilize Transcranial Magnetic Stimulation (TMS) to assess changes in cortical excitability (RMT, MEPs, and cortical silent period). The primary goal is to determine if this combined approach effectively reduces muscle stiffness (measured by the Modified Ashworth Scale) while potentially reducing the total dose of botulinum toxin required per patient.

Detailed description

Background and Rationale: Post-stroke spasticity is a manifestation of Upper Motor Neuron Syndrome, characterized by reduced cortical inhibition and maladaptive plastic changes in both the ipsilesional and contralesional hemispheres. While Botulinum Toxin Type A (BoNT-A) provides focal chemodenervation, its effect on central neurophysiology is an area of active research. This study evaluates a hybrid approach-proximal Phenol neurolysis combined with distal BoNT-A-compared to standard BoNT-A alone. By utilizing Transcranial Magnetic Stimulation (TMS), we aim to investigate how reducing peripheral spasticity influences central motor excitability and interhemispheric inhibition. Methodology and Procedures: Participants (n=60) will be randomized 1:1 into: Group A (Hybrid): Ultrasound-guided Phenol neurolysis (5% aqueous) of the pectoralis and musculocutaneous nerves + distal BoNT-A. Group B (Standard): Ultrasound-guided BoNT-A for all affected upper limb muscles. Bilateral TMS Assessment \& Rationale: Single-pulse TMS will be performed on both the ipsilesional and contralesional hemispheres to evaluate the entire motor network. Ipsilesional Assessment: To measure corticospinal integrity via Resting Motor Threshold (RMT) and Motor Evoked Potential (MEP) amplitude. Contralesional Assessment: To evaluate compensatory over-activity or maladaptive plasticity. Rationale: the investigators hypothesize that effective reduction of spasticity via the hybrid approach will lead to a reduction in the Cortical Silent Period (CSP) and a shift toward normalized interhemispheric balance, potentially reflecting decreased "noise" from the spastic periphery to the cortex. If the ipsilesional MEP is absent, the contralesional hemisphere's excitability will serve as the primary neurophysiological marker. Assessment Time Points: All participants will undergo a comprehensive battery of assessments (Clinical, Functional, and Neurophysiological) at three specific intervals: T0 (Baseline): prior to injection. T1 (Early Follow-up): 4 weeks post-injection (to capture peak BoNT-A and Phenol effect). T2 (Late Follow-up): 12 weeks post-injection (to assess the sustainability of the clinical effect and central plastic changes). Functional \& Clinical Outcomes: Clinical response is measured via the Modified Ashworth Scale (MAS) and Modified Tardieu Scale (MTS). Functional recovery is assessed through the Fugl-Meyer Assessment for Upper Extremity (FMA-UE) and the Goal Attainment Scale (GAS).

Conditions

• Spasticity as Sequela of Stroke

Interventions

Type	Name	Description
PROCEDURE	phenol neurolysis	A chemical neurolysis procedure using a 5% aqueous phenol solution. Under real-time ultrasound (US) guidance, the needle is advanced until it is adjacent to the target nerve trunk. The phenol is then injected to induce protein denaturation and axonal degeneration (Wallerian degeneration), effectively interrupting the spastic reflex arc. Targets: The pectoralis nerves (to address shoulder adduction and internal rotation) and the musculocutaneous nerve (to address elbow flexion). Volume: Typically 1-3 mL per nerve site, adjusted based on patient anatomy and US visualization of the spread.
PROCEDURE	Botulinum Toxin - A injections	A focal chemodenervation procedure using Botulinum Toxin Type A. The toxin is reconstituted with 0.9% sterile saline. Using ultrasound guidance, the medication is injected directly into the motor points of the hypertonic muscles. The toxin acts by inhibiting the release of acetylcholine at the neuromuscular junction, resulting in localized muscle relaxation. Targets (Experimental Group): Distal muscles only (e.g., Flexor Carpi Radialis, Flexor Digitorum Superficialis/Profundus). Targets (Comparator Group): Both proximal (Biceps, Pectoralis) and distal muscles. Dosing: Total dose per muscle is determined based on the Modified Ashworth Scale (MAS) score and muscle volume, following international consensus guidelines.

Timeline

• Start date: 2026-05-01
• Primary completion: 2027-05-30
• Completion: 2027-07-15
• First posted: 2026-02-27
• Last updated: 2026-02-27