Early Botulinum Toxin for Muscle Stiffness Reduction in First-Time Stroke Patients: Improving Recovery and Independence (EARLY BOT-SPAS)

February 5, 2025 updated by: Roberto Carlos Pech Arguelles, Instituto Mexicano del Seguro Social

EVALUATION OF THE EFFECTS OF EARLY APPLICATION OF BOTULINUM TOXIN IN PATIENTS WITH A FIRST CEREBRAL VASCULAR EVENT.

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

200

Phase

  • Early Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: 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.
Drug: 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.
Other Names:
  • AbobotulinumtoxinA
  • BoNT-A
  • Botulinum Neurotoxin A
No Intervention: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Modified Ashworth Scale
Time Frame: Baseline (within 7 days post-stroke) 12 weeks post-intervention 6 months post-intervention 12 months post-intervention

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

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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
MINI MENTAL STATE EXAMINATION
Time Frame: Baseline (within 7 days post-stroke) 12 weeks post-intervention 6 months post-intervention 12 months post-intervention

The Mini-Mental State Examination (MMSE) is a widely used screening tool to assess cognitive function, often employed in stroke rehabilitation studies to monitor neurological recovery. The test evaluates five cognitive domains: orientation, immediate memory, attention and calculation, recall, and language. It includes tasks such as recalling objects, following commands, and answering orientation questions. The MMSE is scored out of 30 points, with higher scores indicating better cognitive function.

A score of 24 or higher is generally considered normal, while scores below this threshold suggest varying degrees of cognitive impairment. The MMSE will be administered at different intervals to assess how early intervention with botulinum toxin and rehabilitation affects patients' cognitive recovery. Its role as a secondary outcome helps determine whether improvements in motor function correlate with cognitive benefits during stroke rehabilitation.
Baseline (within 7 days post-stroke) 12 weeks post-intervention 6 months post-intervention 12 months post-intervention
BARTHEL INDEX
Time Frame: Baseline (within 7 days post-stroke) 12 weeks post-intervention 6 months post-intervention 12 months post-intervention

The Barthel Index is a standardized tool used to assess a patient's level of independence in performing basic activities of daily living (ADLs). It evaluates 10 tasks, including feeding, bathing, dressing, using the toilet, walking, and controlling bladder and bowel movements. Each task is scored based on the patient's ability to perform the activity independently or with assistance. The total score ranges from 0 to 100, with higher scores indicating greater independence.

0 points: Complete dependence 100 points: Full independence
Baseline (within 7 days post-stroke) 12 weeks post-intervention 6 months post-intervention 12 months post-intervention
NIHSS SCALE
Time Frame: BASELINE 1 month post-intervention

The NIHSS Scale is a clinical tool used to assess the severity of neurological deficits in patients who have experienced a stroke. It evaluates multiple domains, including level of consciousness, motor function, sensory abilities, language, coordination, and visual fields. The scale consists of 15 items, each scored from 0 to 4, with a maximum score of 42 indicating severe stroke and a score of 0 indicating no neurological deficits.

Key categories assessed include:

Motor Function: Arm and leg movement Sensory Function: Response to tactile stimuli Language and Speech: Aphasia or dysarthria Level of Consciousness: Alertness and responsiveness
BASELINE 1 month post-intervention
Modified Rankin Scale
Time Frame: Baseline (within 7 days post-stroke) 12 weeks post-intervention 6 months post-intervention 12 months post-intervention

The Modified Rankin Scale (mRS) is a 7-point ordinal scale used to measure functional status and the degree of disability or dependence in activities of daily living following a stroke. It evaluates outcomes ranging from no symptoms (0) to severe disability or death (6). The scale is widely used in stroke rehabilitation to monitor recovery and assess long-term functional outcomes.

Scoring:

0: No symptoms.

  1. No significant disability; able to carry out all usual activities.
  2. Slight disability; unable to perform all previous activities but manages without assistance.
  3. Moderate disability; requires some help but can walk without assistance.
  4. Moderately severe disability; unable to walk or attend to bodily needs without assistance.
  5. Severe disability; requires constant nursing care and attention.
  6. Death.
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
Time Frame: Baseline (within 7 days post-stroke) 12 weeks post-intervention 6 months post-intervention 12 months post-intervention

The Fugl-Meyer Assessment (FMA) for Upper and Lower Extremities is a widely used, validated tool to evaluate motor recovery after stroke. It assesses motor function, balance, sensation, and joint movement through a series of tasks designed to measure impairments in the affected limbs. The assessment is divided into two parts:

  1. Upper Extremity (FMA-UE) Focuses on shoulder, elbow, wrist, hand, and coordination tasks. Tasks are scored from 0 (no function) to 2 (normal function) based on movement ability, precision, and control.

    Maximum score: 66 points for the upper limb.

  2. Lower Extremity (FMA-LE) Evaluates hip, knee, and ankle movement, including weight-bearing tasks and reflex activity.

Similar scoring from 0 to 2 per task, with a maximum score of 34 points for the lower limb.

Key Areas Assessed:

Voluntary Movement: Flexion, extension, and joint movement. Coordination and Speed: Smoothness and accuracy of movements.
Baseline (within 7 days post-stroke) 12 weeks post-intervention 6 months post-intervention 12 months post-intervention
Goal Attainment Scaling
Time Frame: Baseline (within 7 days post-stroke) 6 months post-intervention 12 months post-intervention

Goal Attainment Scaling (GAS) is an individualized, patient-centered tool used to measure the extent to which a patient achieves predetermined rehabilitation goals. It involves setting specific, measurable goals tailored to the patient's condition, which can include improvements in motor function, independence, pain reduction, or daily activities. Each goal is rated on a 5-point scale, ranging from -2 to +2, where:

  • 2: Much less than expected outcome.

  • 1: Somewhat less than expected outcome. 0: Expected outcome achieved.

    • 1: Somewhat better than expected outcome.
    • 2: Much better than expected outcome.
Baseline (within 7 days post-stroke) 6 months post-intervention 12 months post-intervention
MEDICAL RESEARCH COUNCIL
Time Frame: Baseline (within 7 days post-stroke) 12 weeks post-intervention 6 months post-intervention 12 months post-intervention

The MRC Scale is a validated clinical tool used to assess muscle strength in patients with neurological or muscular impairments, such as after a stroke. It evaluates the ability of specific muscle groups to generate force against resistance. Each muscle group is tested, and strength is graded on a 6-point ordinal scale (0 to 5):

0: No muscle contraction observed.

  1. Flicker of contraction, but no visible joint movement.
  2. Active movement possible only with gravity eliminated.
  3. Active movement against gravity, but no resistance.
  4. Active movement against gravity and some resistance.
  5. Normal strength, full movement against maximum resistance.
Baseline (within 7 days post-stroke) 12 weeks post-intervention 6 months post-intervention 12 months post-intervention

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Instituto Mexicano del Seguro Social

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 28, 2025

Primary Completion (Estimated)

February 1, 2027

Study Completion (Estimated)

February 1, 2030

Study Registration Dates

First Submitted

January 31, 2025

First Submitted That Met QC Criteria

January 31, 2025

First Posted (Actual)

March 25, 2025

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

February 5, 2025

Last Verified

February 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • R-2024-3201-072

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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