Comprehensive Observational and Longitudinal study on the Outbreak of Stroke-related Spasticity focusing on the Early Onset management with Botulinum NeuroToxin (COLOSSEO-BoNT): protocol for a real-world prospective observational study on upper limb spasticity

Abstract

Introduction: Poststroke spasticity (PSS) affects up to 40% of patients who had a stroke. Botulinum neurotoxin type A (BoNT-A) has been shown to improve spasticity, but the optimal timing of its application remains unclear. While several predictors of upper limb PSS are known, their utility in clinical practice in relation to BoNT-A treatment has yet to be fully elucidated. The COLOSSEO-BoNT study aims to investigate predictors of PSS and the effects of BoNT-A timing on spasticity-related metrics in a real-world setting.

Methods and analysis: The recruitment will involve approximately 960 patients who have recently experienced an ischaemic stroke (within 10 days, V0) and will follow them up for 24 months. Parameters will be gathered at specific intervals: (V1) 4, (V2) 8, (V3) 12, (V4) 18 months and (V5) 24 months following enrolment. Patients will be monitored throughout their rehabilitation and outpatient clinic journeys and will be compared based on their BoNT-A treatment status-distinguishing between patients receiving treatment at different timings and those who undergo rehabilitation without treatment. Potential predictors will encompass the Fugl-Meyer assessment, the National Institute of Health Stroke Scale (NIHSS), stroke radiological characteristics, performance status, therapies and access to patient care pathways. Outcomes will evaluate muscle stiffness using the modified Ashworth scale and passive range of motion, along with measures of quality of life, pain, and functionality.

Ethics and dissemination: This study underwent review and approval by the Ethics Committee of the Fondazione Policlinico Universitario Campus Bio-Medico, Rome, Italy. Regardless of the outcome, the findings will be disseminated through publication in peer-reviewed journals and presentations at national and international conferences.

Trial registration number: NCT05379413.

Keywords: Clinical trials; NEUROLOGY; PAIN MANAGEMENT; Quality of Life; REHABILITATION MEDICINE; STROKE MEDICINE.

Figure 1. The COLOSSEO-BoNT study flow chart. *Estimated sample size across time points and stratification; Q1, first quartile of time from stroke distribution; Q3, third quartile of time from stroke distribution. BoNT, botulinum neurotoxin type A; PSS, poststroke spasticity.

Figure 2. Schematic description of study visits and collected information. (A) Anamnestic information including age, sex, hand dominance, heigh, weigh and BMI, smoking habits, presence of diabetes, atrial fibrillation, hypertension, carotid pathology, chronic obstructive pulmonary disease, chronic kidney injury, seizures, coronary artery disease and related therapies (anticoagulants, antiplatelet agents); (A’) update on comorbid condition and related therapies; (B) Radiological predictors of spasticity including stroke size and location, internal capsule involvement, Fazekas score; (C) Clinical predictors of spasticity including: NIHSS, modified Rankin scale, Barthel index, MMSE, Fugl-Meyer Assessment, baseline modified Ashworth scale; (C’) update on clinical predictors; (D) spasticity outcome measures and related index of functionality and quality of life: modified Ashworth scale, Arm Activity measures (ARMA) scale, Euro-Quality of life 5 Dimension (EQ-5D) scale, pain scale (visual analogue scale, VAS); (E) information on BoNT-A therapy: BoNT-A type, dosage, selected muscles and use of guidance; (F) concomitant therapies including rehabilitation: physical therapies setting, the number of rehabilitation treatments per week, access to robotic rehabilitation, use of spasticity medications. BoNT-A treatments could be recorded at any time during the follow-up as extra visits (EV). Adverse events are collected at any time point and visit. BMI, body mass index; BoNT-A, botulinum neurotoxin type A; MMSE, Mini-Mental State Examination; NIHSS, National Institute of Health Stroke Scale.