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

NCT ID: NCT06811142

Last Updated: 2025-02-10

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 200 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-01-28
• Study Completion Date: 2030-02-01

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.

Detailed Description

This clinical study evaluates the impact of early application of botulinum toxin on patients experiencing their first cerebrovascular event. Spasticity, characterized by abnormal muscle stiffness and involuntary muscle contractions, is a frequent complication of strokes that can lead to reduced mobility, pain, joint deformities, and a diminished ability to perform daily activities. The study aims to determine whether early intervention with botulinum toxin, in combination with rehabilitation therapy, can mitigate the development and severity of post-stroke spasticity, improve muscle tone, and enhance functional outcomes.

Patients eligible for participation include men and women aged 18 and older, admitted with a confirmed diagnosis of a recent stroke within the first seven days of symptom onset. The intervention will involve botulinum toxin injections administered within the early subacute phase (up to 12 weeks post-stroke) to maximize the neuroplastic window and reduce the risk of permanent muscle contractures. The study will be conducted over three years at the Regional General Hospital No. 1 "Lic. Ignacio García Téllez," Mérida, Yucatán.

The primary outcomes assessed will include changes in muscle tone, evaluated by the Modified Ashworth Scale (MAS), and functional independence, measured using the Barthel Index. Secondary outcomes will assess quality of life, cognitive performance, and overall rehabilitation progress through tools such as the Mini-Mental State Examination (MMSE) and the Fugl-Meyer Assessment Scale. The study design is a prospective, controlled clinical trial comparing patients receiving early botulinum toxin injections with those undergoing standard rehabilitation only.

This research aims to provide valuable clinical evidence regarding the effectiveness of early botulinum toxin application in preventing long-term disabilities, enhancing recovery, and reducing healthcare burdens associated with post-stroke spasticity. By identifying clinical predictors of spasticity, the study will contribute to the development of targeted, time-sensitive interventions that optimize stroke rehabilitation outcomes.

Conditions

Spasticity; Stroke; Neurological Rehabilitation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

intervention

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.

Group Type: ACTIVE_COMPARATOR

Botulinum Toxin Type A (BoNT-A)

Intervention Type: 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.

control

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.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Botulinum Toxin Type A (BoNT-A)

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.

Intervention Type: DRUG

Other Intervention Names

Botulinum Neurotoxin A; BoNT-A; AbobotulinumtoxinA

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Instituto Mexicano del Seguro Social

OTHER_GOV

Sponsor Role: lead

Responsible Party

Roberto Carlos Pech Arguelles

principal investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

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

Mérida, Yucatán, Mexico

Countries

Mexico

References

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.

Reference Type: RESULT

PMID: 22200394 (View on PubMed)

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.

Reference Type: RESULT

PMID: 26276377 (View on PubMed)

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.

Reference Type: RESULT

PMID: 27547509 (View on PubMed)

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.

Reference Type: RESULT

PMID: 33551975 (View on PubMed)

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.

Reference Type: RESULT

PMID: 27871449 (View on PubMed)

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.

Reference Type: RESULT

PMID: 33106968 (View on PubMed)

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

Reference Type: 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.

Reference Type: RESULT

PMID: 33057730 (View on PubMed)

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.

Reference Type: RESULT

PMID: 29753889 (View on PubMed)

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.

Reference Type: RESULT

PMID: 33923397 (View on PubMed)

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.

Reference Type: RESULT

PMID: 33978513 (View on PubMed)

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.

Reference Type: RESULT

PMID: 33156735 (View on PubMed)

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

Reference Type: RESULT

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

Reference Type: 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.

Reference Type: RESULT

PMID: 20360543 (View on PubMed)

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

Reference Type: RESULT

Provided Documents

Document Type: Study Protocol, Statistical Analysis Plan, and Informed Consent Form

View Document

Other Identifiers

R-2024-3201-072

Identifier Type: -

Identifier Source: org_study_id