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

NCT07440173 | Not Yet Recruiting Phase 4

• 1 other identifier: NuroRehabSpasticity
• Study Type: interventional
• Target: 60
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Spasticity as Sequela of Stroke

Keywords

Phenol Neurolysis; Botulinum Toxin Type A; Transcranial Magnetic Stimulation (TMS); Cortical Excitability; Upper Limb Rehabilitation; Ultrasound-Guided Injection

Outcome Measures

Primary Outcomes (1)

• Change from Baseline in the Modified Ashworth Scale (MAS) at 4 and 12 weeks.

  The MAS is used to assess muscle spasticity on a scale from 0 to 4. We will calculate the mean change in scores from baseline to each follow-up point. Lower scores indicate a reduction in muscle tone.

  Baseline, 4 weeks, and 12 weeks.

Secondary Outcomes (5)

• Change from Baseline in Fugl-Meyer Assessment for Upper Extremity (FMA-UE).

  Baseline, 4 weeks, and 12 weeks.

• Goal Attainment Scale (GAS).

  4 weeks and 12 weeks.

• Change from Baseline in Resting Motor Threshold (RMT) of both hemispheres.

  Baseline, 4 weeks, and 12 weeks.

• Change from Baseline in Cortical Silent Period (CSP) duration.

  Baseline, 4 weeks, and 12 weeks.

• Total Dose of Botulinum Toxin Type A (BoNT-A) administered.

  Day 0 (at time of injection).

Study Arms (2)

Hybrid Neuro-Chemodenervation (Phenol + BoNT-A)

EXPERIMENTAL

Participants in this arm will receive a combined treatment approach. Phenol neurolysis (5% aqueous solution) will be administered under ultrasound guidance to the proximal nerves (specifically the pectoralis nerves for shoulder spasticity and the musculocutaneous nerve for elbow flexor spasticity). Concurrently, Botulinum Toxin Type A (BoNT-A) will be injected into the distal forearm flexor muscles (e.g., Flexor Carpi Radialis, Flexor Carpi Ulnaris, and Flexor Digitorum Profundus/Sublimis) to address wrist and finger spasticity.

Procedure: phenol neurolysis; Procedure: Botulinum Toxin - A injections

Standard Chemodenervation (BoNT-A Alone)

ACTIVE COMPARATOR

Participants in this arm will receive the standard-of-care treatment consisting of Botulinum Toxin Type A (BoNT-A) injections alone. The toxin will be administered under ultrasound guidance to all clinically indicated upper limb muscles, including both proximal (e.g., Pectoralis major, Biceps brachii) and distal muscle groups (e.g., forearm flexors), following standard clinical dosing guidelines.

Procedure: Botulinum Toxin - A injections

Interventions

phenol neurolysis PROCEDURE

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.

Hybrid Neuro-Chemodenervation (Phenol + BoNT-A)

Botulinum Toxin - A injections PROCEDURE

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.

Hybrid Neuro-Chemodenervation (Phenol + BoNT-A); Standard Chemodenervation (BoNT-A Alone)

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults aged 18 to 70 years.
• Diagnosis: Documented Ischemic or Hemorrhagic stroke (with a duration of at least 6 months post-stroke to ensure a chronic, stable phase).
• Spasticity Severity: A score of 2 on the Modified Ashworth Scale (MAS) in at least one proximal muscle group (Shoulder adductors or Elbow flexors).
• Functional Status: Evidence of upper limb motor impairment but with enough stability to participate in follow-up.
• Cognitive Ability: Ability to understand and follow instructions (Mini-Mental State Examination score typically 24) to ensure cooperation during TMS and functional testing.
• Consent: Signed informed consent provided by the patient or a legal guardian.

You may not qualify if:

• Fixed Contractures: Any permanent joint deformity or fixed contracture in the target limb that would prevent range of motion improvement.
• Prior Treatment: Received Botulinum Toxin or phenol injections in the affected limb within the last 6 months.
• TMS Contraindications: History of seizures.
• Presence of metallic implants in the head or neck (e.g., clips, shunts).
• Cardiac pacemakers or implanted medication pumps.
• Local Factors:Skin infection or inflammation at the planned injection sites.
• Medical Co-morbidities: Significant peripheral nerve disease (other than the stroke-related upper motor neuron lesion) or severe psychiatric disorders.
• Phenol Sensitivity: Known hypersensitivity to phenol or its derivatives.

Sponsors & Collaborators

• Assiut University: lead

Related Publications (5)

• Anwar F, Ramanathan S. Combined Botulinum Toxin Injections and Phenol Nerve / Motor Point Blocks to Manage Multifocal Spasticity in Adults. British Journal of Medical Practitioners. March 2017;10(1):a1002.

  BACKGROUND

• Murase N, Duque J, Mazzocchio R, Cohen LG. Influence of interhemispheric interactions on motor function in chronic stroke. Ann Neurol. 2004 Mar;55(3):400-9. doi: 10.1002/ana.10848.

  PMID: 14991818 BACKGROUND

• Rossini PM, Burke D, Chen R, Cohen LG, Daskalakis Z, Di Iorio R, Di Lazzaro V, Ferreri F, Fitzgerald PB, George MS, Hallett M, Lefaucheur JP, Langguth B, Matsumoto H, Miniussi C, Nitsche MA, Pascual-Leone A, Paulus W, Rossi S, Rothwell JC, Siebner HR, Ugawa Y, Walsh V, Ziemann U. Non-invasive electrical and magnetic stimulation of the brain, spinal cord, roots and peripheral nerves: Basic principles and procedures for routine clinical and research application. An updated report from an I.F.C.N. Committee. Clin Neurophysiol. 2015 Jun;126(6):1071-1107. doi: 10.1016/j.clinph.2015.02.001. Epub 2015 Feb 10.

  PMID: 25797650 RESULT

• Gonnade N, Lokhande V, Ajij M, Gaur A, Shukla K. Phenol Versus Botulinum Toxin A Injection in Ambulatory Cerebral Palsy Spastic Diplegia: A Comparative Study. J Pediatr Neurosci. 2017 Oct-Dec;12(4):338-343. doi: 10.4103/jpn.JPN_123_17.

  PMID: 29675072 RESULT

• Wissel J, Ward AB, Erztgaard P, Bensmail D, Hecht MJ, Lejeune TM, Schnider P, Altavista MC, Cavazza S, Deltombe T, Duarte E, Geurts AC, Gracies JM, Haboubi NH, Juan FJ, Kasch H, Katterer C, Kirazli Y, Manganotti P, Parman Y, Paternostro-Sluga T, Petropoulou K, Prempeh R, Rousseaux M, Slawek J, Tieranta N. European consensus table on the use of botulinum toxin type A in adult spasticity. J Rehabil Med. 2009 Jan;41(1):13-25. doi: 10.2340/16501977-0303.

  PMID: 19197564 RESULT

Study Officials

• Mohammad Korayem, Master's degree

  Assiut University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mohammad Ahmad Korayem, Master's degree

CONTACT

+201021478054; Mohammadkorayem@aun.edu.eg

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: The investigator responsible for performing the clinical assessments (Modified Ashworth Scale, Modified Tardieu Scale, Fugl-Meyer Assessment) and the neurophysiological measurements (Transcranial Magnetic Stimulation) will be blinded to the treatment allocation of each participant. The blinding protocol will be maintained as follows: 1. The randomized group assignment will be kept in a secure, opaque folder by the primary injector (Care Provider). 2. All injections will be performed in a separate procedure room. 3. Assessments will be conducted in a different clinic space to ensure the assessor does not witness the procedure. 4. Participants will be instructed not to disclose the nature of their injection (e.g., number of injection sites) to the assessor during the follow-up visits at 4 and 12 weeks.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant lecturer

Model Details: A prospective, randomized, parallel-group, assessor-blinded controlled trial. A total of 60 participants will be recruited and randomized using a computer-generated randomization sequence into two equal groups (n=30 each). Group A (Experimental): Participants receive a combination of ultrasound-guided phenol neurolysis for proximal upper limb spasticity and Botulinum Toxin Type A (BoNT-A) for distal muscle spasticity. Group B (Active Comparator): Participants receive ultrasound-guided BoNT-A injections for all affected upper limb muscles (both proximal and distal). Clinical, functional, and neurophysiological (TMS) assessments are conducted at baseline, 4 weeks, and 12 weeks post-intervention. To ensure scientific rigor, the clinical and TMS assessments will be performed by a blinded investigator who is unaware of the group allocation.

Study Record Dates

• First Submitted: February 20, 2026
• First Posted: February 27, 2026
• Study Start: May 1, 2026
• Primary Completion (Estimated): May 30, 2027
• Study Completion (Estimated): July 15, 2027
• Last Updated: February 27, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share