Early Botulinum Toxin for Muscle Stiffness Reduction in First-Time Stroke Patients: Improving Recovery and Independence

NCT06811142 | Active Not Recruiting Early Phase 1 DMC

• 1 other identifier: R-2024-3201-072
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

This study examines the early use of botulinum toxin in patients recovering from their first stroke to help reduce muscle stiffness and improve mobility. Spasticity, a condition that causes abnormal muscle tightness, is a common complication following strokes. It can result in decreased independence, pain, joint contractures, and difficulty performing daily activities. Early intervention is critical to prevent long-term complications and improve recovery outcomes.The participants are men and women aged 18 and older who have recently experienced their first stroke. These patients, admitted to the Regional General Hospital No. 1 "Lic. Ignacio García Téllez" in Mérida, Yucatán, will receive botulinum toxin injections alongside a comprehensive rehabilitation program. Botulinum toxin, commonly known for its muscle-relaxing effects, will be administered within the first three months after the stroke. This early timeline aims to maximize recovery by addressing muscle tightness before it worsens.The study will evaluate how the combination of botulinum toxin and physical therapy affects muscle tone, functional independence, and overall quality of life. Key measurements include the Modified Ashworth Scale (MAS) to assess muscle stiffness, the Barthel Index to evaluate daily activity independence, and cognitive assessments to monitor brain recovery. Patients' progress will be tracked over several months to measure the intervention's short, medium, and long-term impact.Previous research suggests that early application of botulinum toxin can prevent long-lasting muscle contractures and improve mobility, but more studies are needed to confirm its benefits in stroke rehabilitation. The results of this research could help establish early botulinum toxin injections as a standard practice in stroke recovery programs, reducing disability and healthcare costs while improving the lives of stroke survivors.

Conditions

Spasticity; Stroke; Neurological Rehabilitation

Keywords

NEUROPLASTICITY; Post-Stroke Spasticity; Stroke Rehabilitation; Early Intervention; Botulinum Toxin (BoNT-A); Modified Ashworth Scale

Outcome Measures

Primary Outcomes (2)

• Modified Ashworth Scale

  The Modified Ashworth Scale (MAS) is a 6-point ordinal scale (0, 1, 1+, 2, 3, 4) used to assess spasticity by evaluating resistance during passive movement of a joint. The scoring system is as follows: 0: No increase in muscle tone. 1: Slight increase in tone, with a catch and release or minimal resistance at the end of the range of motion. 1+: Slight increase in tone, with a catch followed by minimal resistance throughout less than half of the range of motion. 2: More marked increase in tone through most of the range, but the joint moves easily. 3: Considerable increase in tone, making passive movement difficult. 4: Affected part is rigid in flexion or extension.

  Baseline (within 7 days post-stroke) 12 weeks post-intervention 6 months post-intervention 12 months post-intervention

• MODIFIED TARDIEU SCALE

  The Modified Tardieu Scale (MTS) assesses spasticity by measuring muscle response to passive stretching at different velocities. It evaluates both the angle of muscle reaction (R1) and the final range of motion (R2). The key feature of the MTS is its sensitivity to velocity-dependent resistance, distinguishing it from the Modified Ashworth Scale. Joint movement is tested at three speeds: slow (V1), normal (V2), and fast (V3). The difference between R1 and R2 reflects dynamic spasticity and muscle stiffness. The scale assigns qualitative scores (0-5) based on the severity of the muscle reaction: 0: No resistance throughout the movement. 1. Slight resistance with no clear catch. 2. Clear catch at a precise angle, followed by release. 3. Fatigable clonus with fewer than 10 seconds of contraction. 4. Unfatigable clonus lasting more than 10 seconds. 5. Joint is immobile.

  Baseline (within 7 days post-stroke) 8 weeks post-intervention 12 weeks post-intervention 6 months post-intervention 12 months post-intervention

Secondary Outcomes (7)

• MINI MENTAL STATE EXAMINATION

  Baseline (within 7 days post-stroke) 12 weeks post-intervention 6 months post-intervention 12 months post-intervention

• BARTHEL INDEX

  Baseline (within 7 days post-stroke) 12 weeks post-intervention 6 months post-intervention 12 months post-intervention

• NIHSS SCALE

  BASELINE 1 month post-intervention

• Modified Rankin Scale

  Baseline (within 7 days post-stroke) 12 weeks post-intervention 6 months post-intervention 12 months post-intervention

• Fugl-Meyer Upper and Lower Extremity Scale

  Baseline (within 7 days post-stroke) 12 weeks post-intervention 6 months post-intervention 12 months post-intervention

Study Arms (2)

intervention

ACTIVE COMPARATOR

Participants in the intervention group will receive early botulinum toxin type A (BoNT-A) injections in addition to a standard rehabilitation program. The botulinum toxin will be administered within the first 12 weeks following stroke onset, targeting muscles affected by spasticity. The injections aim to reduce abnormal muscle tone, prevent contractures, and improve functional mobility. Rehabilitation therapy will include physical exercises, range-of-motion activities, and muscle-strengthening interventions tailored to individual recovery needs. The combined therapy is designed to optimize motor function, promote neuroplasticity, and improve overall independence and quality of life.

Drug: Botulinum Toxin Type A (BoNT-A)

control

NO INTERVENTION

Participants in the control group will undergo a standard rehabilitation program without the early application of botulinum toxin. The rehabilitation will consist of physical therapy focused on improving muscle strength, range of motion, and functional independence. Treatment will be tailored to each participant's condition and recovery progress, following established post-stroke rehabilitation protocols. This group will serve as the comparator to evaluate the additional benefits of early botulinum toxin intervention.

Interventions

Botulinum Toxin Type A (BoNT-A) DRUG

This intervention involves the early administration of botulinum toxin type A (BoNT-A) within the first 12 weeks after a cerebrovascular event. The injections target muscles affected by spasticity, aiming to reduce abnormal tone, prevent contractures, and improve functional mobility. BoNT-A works by blocking acetylcholine release at the neuromuscular junction, resulting in muscle relaxation. Ultrasound guidance or anatomical landmarks will be used for accurate injection. This early intervention capitalizes on the neuroplastic window and is combined with standard rehabilitation to enhance motor recovery and prevent long-term complications.

Also known as: Botulinum Neurotoxin A, BoNT-A, AbobotulinumtoxinA

intervention

Eligibility Criteria

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

You may qualify if:

• Men and women ≥18 years old. Beneficiaries treated in the Emergency and/or Internal Medicine service at HGR No. 1, IMSS Mérida, Yucatán, with an acute stroke confirmed by clinical symptoms and a new ischemic lesion detected through magnetic resonance imaging or computed tomography within 7 days of onset.

You may not qualify if:

• Severe cognitive deficits.
• Severe language comprehension disorders.
• Lack of capacity to give informed consent.
• Physical disability already existing before the acute stroke.
• Subarachnoid hemorrhage.
• Transient ischemic attack.
• Any other neurological disorder that could affect muscle tone (Conditions related to the spine, brain infection and traumatic brain injury).
• Any amputation of the limb on the affected side.
• Peripheral neuropathy of the upper and/or lower limbs.
• Patients who have suffered a previous stroke.

Sponsors & Collaborators

• Instituto Mexicano del Seguro Social: lead

Study Sites (1)

Hospital General Regional No.1 "Lic. Ignacio García Téllez" IMSS, Calle 41 101, Fénix, 97155 Mérida, Yuc.

Mérida, Yucatán, 97155, Mexico

Location

Related Publications (16)

• Kong KH, Lee J, Chua KS. Occurrence and temporal evolution of upper limb spasticity in stroke patients admitted to a rehabilitation unit. Arch Phys Med Rehabil. 2012 Jan;93(1):143-8. doi: 10.1016/j.apmr.2011.06.027.

  PMID: 22200394 RESULT

• Opheim A, Danielsson A, Alt Murphy M, Persson HC, Sunnerhagen KS. Early prediction of long-term upper limb spasticity after stroke: part of the SALGOT study. Neurology. 2015 Sep 8;85(10):873-80. doi: 10.1212/WNL.0000000000001908. Epub 2015 Aug 14.

  PMID: 26276377 RESULT

• Sunnerhagen KS. Predictors of Spasticity After Stroke. Curr Phys Med Rehabil Rep. 2016;4:182-185. doi: 10.1007/s40141-016-0128-3. Epub 2016 Jul 22.

  PMID: 27547509 RESULT

• Zeng H, Chen J, Guo Y, Tan S. Prevalence and Risk Factors for Spasticity After Stroke: A Systematic Review and Meta-Analysis. Front Neurol. 2021 Jan 20;11:616097. doi: 10.3389/fneur.2020.616097. eCollection 2020.

  PMID: 33551975 RESULT

• Rosales RL, Efendy F, Teleg ES, Delos Santos MM, Rosales MC, Ostrea M, Tanglao MJ, Ng AR. Botulinum toxin as early intervention for spasticity after stroke or non-progressive brain lesion: A meta-analysis. J Neurol Sci. 2016 Dec 15;371:6-14. doi: 10.1016/j.jns.2016.10.005. Epub 2016 Oct 11.

  PMID: 27871449 RESULT

• Patel AT, Ward AB, Geis C, Jost WH, Liu C, Dimitrova R. Impact of early intervention with onabotulinumtoxinA treatment in adult patients with post-stroke lower limb spasticity: results from the double-blind, placebo-controlled, phase 3 REFLEX study. J Neural Transm (Vienna). 2020 Dec;127(12):1619-1629. doi: 10.1007/s00702-020-02251-6. Epub 2020 Oct 27.

  PMID: 33106968 RESULT

• 11. Stephen, AD (sf). Spasticity in adults: management using botulinum toxin. Royal College of Physicians, 3-22.

  RESULT

• Francisco GE, Balbert A, Bavikatte G, Bensmail D, Carda S, Deltombe T, Draulans N, Escaldi S, Gross R, Jacinto J, Ketchum N, Molteni F, Moraleda S, ODell MW, Reebye R, Satero P, Verduzco-Gutierrez M, Walker H, Wissel J. A practical guide to optimizing the benefits of post-stroke spasticity interventions with botulinum toxin A: An international group consensus. J Rehabil Med. 2021 Jan 1;53(1):jrm00134. doi: 10.2340/16501977-2753.

  PMID: 33057730 RESULT

• Sunnerhagen KS, Opheim A, Alt Murphy M. Onset, time course and prediction of spasticity after stroke or traumatic brain injury. Ann Phys Rehabil Med. 2019 Nov;62(6):431-434. doi: 10.1016/j.rehab.2018.04.004. Epub 2018 May 16.

  PMID: 29753889 RESULT

• Ganguly J, Kulshreshtha D, Almotiri M, Jog M. Muscle Tone Physiology and Abnormalities. Toxins (Basel). 2021 Apr 16;13(4):282. doi: 10.3390/toxins13040282.

  PMID: 33923397 RESULT

• Li S, Francisco GE, Rymer WZ. A New Definition of Poststroke Spasticity and the Interference of Spasticity With Motor Recovery From Acute to Chronic Stages. Neurorehabil Neural Repair. 2021 Jul;35(7):601-610. doi: 10.1177/15459683211011214. Epub 2021 May 12.

  PMID: 33978513 RESULT

• Glaess-Leistner S, Ri SJ, Audebert HJ, Wissel J. Early clinical predictors of post stroke spasticity. Top Stroke Rehabil. 2021 Oct;28(7):508-518. doi: 10.1080/10749357.2020.1843845. Epub 2020 Nov 6.

  PMID: 33156735 RESULT

• 4. Marlenne, RS (2015). In-hospital mortality due to cerebrovascular diseases in the main public health institutions in Mexico. CONAMED-PAHO BULLETIN, 7-11

  RESULT

• 3. Cuadrado, A. (2009). Stroke rehabilitation: assessment, prognosis and treatment. Galicia Clinic/Galician Society of Internal Medicine, 25-34.

  RESULT

• Cantu-Brito C, Majersik JJ, Sanchez BN, Ruano A, Quinones G, Arzola J, Morgenstern LB. Hospitalized stroke surveillance in the community of Durango, Mexico: the brain attack surveillance in Durango study. Stroke. 2010 May;41(5):878-84. doi: 10.1161/STROKEAHA.109.577726. Epub 2010 Apr 1.

  PMID: 20360543 RESULT

• 1. Parra, JA (2019). Ischemic stroke: extensive review of the literature for the primary care physician. Med Int Méx, 61-63.

  RESULT

MeSH Terms

Conditions

Muscle Spasticity; Stroke

Interventions

Botulinum Toxins, Type A; incobotulinumtoxinA; abobotulinumtoxinA

Condition Hierarchy (Ancestors)

Muscular Diseases; Musculoskeletal Diseases; Muscle Hypertonia; Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Botulinum Toxins; Metalloendopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Metalloproteases; Bacterial Proteins; Proteins; Amino Acids, Peptides, and Proteins; Bacterial Toxins; Toxins, Biological; Biological Factors

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: principal investigator

Model Details: This study uses a Parallel Assignment Model with two groups: an intervention group receiving early botulinum toxin (BoNT-A) injections and a control group undergoing standard rehabilitation without the toxin. The intervention aims to prevent spasticity-related complications by leveraging early treatment during the neuroplastic phase, within 12 weeks post-stroke. Randomized and controlled conditions will ensure unbiased results, with outcomes measured over short, medium, and long-term follow-up periods.

Study Record Dates

• First Submitted: January 31, 2025
• First Posted: February 6, 2025
• Study Start: January 28, 2025
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): February 1, 2030
• Last Updated: February 10, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

ME (1)