Observational Longitudinal Study on the Outbreak and Management of Stroke Related Spasticity (COLOSSEO)

Comprehensive Observational & Longitudinal Study on the Outbreak of Stroke Related Spasticity Focusing on the Early Onset Management With BoNT: The COLOSSEO-BoNT Study

Stroke is one of the leading cause of death and disability worldwide. Post-stroke spasticity (PSS) is outbreak after a stroke and is featured by disabling muscle stiffness. PSS could manifest in up tp 50% cases within 6 months after a stroke, especially in the upper limb. Despite it is an acknowledged condition it is insufficiently recognized and treated in clinical practice.

Focal and regional spasticity could improve with rehabilitation and in selected cases with botulinum neurotoxin (BoNT) type A injections. The latter causes muscle relaxation and fosters neuroplasticity, which is able in turn of ameliorating several patient functional aspects. Recent literature demonstrated that PSS patients treated with early BoNT (within 3 month since PSS outbreak) could improve in their clinical status better than patients with a later treatment.

An earlier recognition of PSS predictors could improve patient management. Hence, the investigators are going to perform a multicentric prospective observational real life study with BoNT, based on the best clinical practice and aimed at the early recognition and management of PSS through the identification of 1) early clinical predictors of spasticity (collected within 10 days since stroke), 2) BoNT clinical outcome relative to the timing of the treatment

Study Overview

• Status: Not yet recruiting
• Conditions: Spasticity as Sequela of Stroke
• Intervention / Treatment: Drug: Botulinum toxin type A

• Study Type: Observational
• Enrollment (Anticipated): 960

Contacts and Locations

• Study Contact: Name: Massimo Marano, MD; Phone Number: +3906225411220; Email: m.marano@policlinicocampus.it

Study Locations

• Italy
  • Lazio
    • Roma, Lazio, Italy, 00100
      • ASL RM 1 San Filippo Neri Hospital
      • Contact: Maria Concetta Altavista, MD; Email: mc.altavista@gmail.com
    • Roma, Lazio, Italy, 00100
      • Sapienza University of Rome - Stroke Unit
      • Contact: Danilo Toni, MD; Email: danilo.toni@uniroma1.it
    • Roma, Lazio, Italy, 00100
      • Sapienza University of Rome
      • Contact: Antonio Suppa, MD; Email: antonio.suppa@uniroma1.it
    • Roma, Lazio, Italy, 00128
      • Fondazione Policlinico Universitario Campus Bio-medico
      • Contact: Massimo Marano, MD; Email: m.marano@policlinicocampus.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients suffering for ischemic stroke with upper limb involvement treated at the Lazio region (Italy) stroke units.

Description

Inclusion Criteria:

• Ischemic stroke with onset not far than 10 days before the enrollment
• BoNT naive
• Ability to sign the informed consent

Exclusion Criteria:

• Hypersensitivity to BoNT or BoNT related substances
• Participant of Post-stroke spasticity RCT
• Persistent and severe altered mental status or concurrent severe medical condition able to hasten the rehabilitation path.

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Early BoNT treatment; Patients with PSS treated with BoNT within the first Quartile of injection timing distribution	Drug: Botulinum toxin type A; Botulinum neurotoxin (BoNT) Type A injection with either OnaBoNT-A, AboBoNT-A, IncoBoNT-A
Late BoNT treatment; Patients with PSS treated with BoNT within the third Quartile of injection timing distribution	Drug: Botulinum toxin type A; Botulinum neurotoxin (BoNT) Type A injection with either OnaBoNT-A, AboBoNT-A, IncoBoNT-A
Not treated with BoNT; Natural controls with PSS not treated with BoNT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Upper limb post stroke-spasticity development	Detection of a Modified Ashworth Scale (MAS) >/= 1 at the upper limb (MAS is a 0 to 5 score, with score 5 as the worst rigidity possible)	0-24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Post-Stroke Spasticity in early vs late treatment	Comparison of the Modified Ashworth Scale (MAS) at the elbow and wrist (MAS is a 0 to 5 score, with score 5 as the worst rigidity possible) in early versus late treatment	3-24 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Upper limb functionality	Comparison of functional items of upper limb functionality (arm activity measure scale, i.e. ARM-A a 0-84 scale - a higher score means a worse upper limb function) of early versus late treatments	3-24 months
Quality of Life measurement	Comparison of Quality of Life (EuroQoL-5D or EQ-5D scale , 5 to 25 scale where 25 is the worst quality of life possible) of patients with early versus late treatments	3-24 months
Pain measurement	Comparison of pain (Visual Analogue scale or VAS in units on a 0-10 grading system, where 10 is the worst pain possible) of patients with early versus late treatments	3-24 months
Spasticity in Botulinum Toxin (BoNT) treated versus untreated patients	Comparison of modified ashworth scale (MAS) in BoNT treated versus untreated subjects (MAS is a 0 to 5 score, where 5 is the worst rigidity possible). Herein an aggregated wrist and elbow score (on a 0 - 10 scale with 10 being the worst spasticity) will be used.	3-24 months
Functionality in Botulinum Toxin treated versus untreated patients	Comparison of functionality (arm activity measure, i.e. ARM-A total score, a 0 to 84 scoring system - higher score means a worse upper limb function) in BoNT treated versus untreated subjects	3-24 months
Quality of life in Botulinum Toxin treated versus untreated patients	Comparison of Quality of life (EuroQoL-5D or EQ-5D scale is a 5 to 25 scale where 25 is the lower quality of life possible) in BoNT treated versus untreated patients	3-24 months
Pain in Botulinum Toxin treated versus untreated patients	Comparison of pain (visual analogue scale, VAS, 0-10 scale where 10 is the worst pain possible) in BoNT treated versus untreated patients	3-24 months

Collaborators and Investigators

• Sponsor: Campus Bio-Medico University

Publications and helpful links

General Publications

• 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.
• Wissel J, Fheodoroff K, Hoonhorst M, Mungersdorf M, Gallien P, Meier N, Hamacher J, Hefter H, Maisonobe P, Koch M. Effectiveness of AbobotulinumtoxinA in Post-stroke Upper Limb Spasticity in Relation to Timing of Treatment. Front Neurol. 2020 Feb 28;11:104. doi: 10.3389/fneur.2020.00104. eCollection 2020.
• Picelli A, Santamato A, Cosma M, Baricich A, Chisari C, Millevolte M, Prete CD, Mazzu I, Girardi P, Smania N. Early Botulinum Toxin Type A Injection for Post-Stroke Spasticity: A Longitudinal Cohort Study. Toxins (Basel). 2021 May 24;13(6):374. doi: 10.3390/toxins13060374.
• 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.

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): June 1, 2022
• Primary Completion (ANTICIPATED): June 1, 2025
• Study Completion (ANTICIPATED): June 1, 2025

Study Registration Dates

• First Submitted: May 10, 2022
• First Submitted That Met QC Criteria: May 13, 2022
• First Posted (ACTUAL): May 18, 2022

Study Record Updates

• Last Update Posted (ACTUAL): May 23, 2022
• Last Update Submitted That Met QC Criteria: May 17, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: Rehabilitation; Stroke; Botulinum neurotoxin type A (BoNT-A); Post-Stroke Spasticity (PSS)
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Manifestations; Muscle Hypertonia; Stroke; Muscle Spasticity; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Cholinergic Agents; Membrane Transport Modulators; Acetylcholine Release Inhibitors; Neuromuscular Agents; Botulinum Toxins; Botulinum Toxins, Type A; abobotulinumtoxinA
• Other Study ID Numbers: COLOSSEO-BoNT

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: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No