Botulinum Toxin in Patients With Spastic Lower Limb Paresis Associated With Multiple Sclerosis

Effectiveness of Botulinum Toxin Type A Infiltrations in the Gait and Quality of Life in Adults With Spastic Lower Limb Paresis Secondary to Multiple Sclerosis

Spastic paraparesis is one of the most disabling functional deficits in the population with multiple sclerosis between 18 and 80 years of age and at any functional level. Infiltration with Botulinum Toxin is a clinical practice that has been carried out for years with clinical evidence of improvement in the patient's walking patterns and quality of life. We assume that the infiltration of this product can generate a direct benefit in the walking ability of these patients and secondarily improve their quality of life.

Study Overview

• Status: Completed
• Conditions: Multiple Sclerosis
• Intervention / Treatment: Drug: Botulinum toxin type A infiltrations

• Study Type: Interventional
• Enrollment (Actual): 84
• Phase: Phase 3

Contacts and Locations

Study Locations

• Spain
  • Madrid, Spain, 28006
    • Hospital Universitario de la Princesa
  • Madrid
    • Majadahonda, Madrid, Spain, 28220
      • Hospital Universitario Puerta de Hierro

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Acceptance and signature of informed consent.
• Age between 18 and 80 years old, both included.
• Patients with relapsing remitting multiple sclerosis (RRMS), progressive secondary (SP) and primary progressive (PP), with spasticity resistant to usual treatment, either because of the severity of the spasticity or because of intolerance to side effects.
• Outpatients with spastic paraparesis that causes gait deficiency.
• Patients with an EDSS score between 2 and 6, both included.
• Patients with segmental involvement in MAS >1 in two or more muscle groups in the lower extremities.
• Absence of cognitive disability. Score less than 5 on the SPMSQ scale of Pfeiffer.
• Possibility of carrying out the treatment (method of administration, scheduled visits) and scales correctly.
• Women of childbearing potential should use an effective contraceptive method (hormonal contraceptives, intrauterine device, condom) or refrain from having sex in order not to get pregnant. A woman is considered to be fertile after menarche and to become postmenopausal, unless she has undergone a permanent sterilization procedure (hysterectomy, salpingectomy, bilateral oophorectomy). A postmenopausal state is defined as absence of menstruation for 12 months without an alternative medical cause.

Exclusion Criteria:

• Psychiatric illness that hinders participation in the trial.
• Comorbidity that threatens the patient's life in the short term (severe liver disease, cardiovascular disease, etc.).
• Osteoarticular disorder that prevents physical activity.
• Pregnancy or lactation.
• Lack of primary or secondary response to any type of Botulinum Toxin for the treatment of MS previously detected.
• Sensitivity to Botulinum Toxin or to any excipient.
• Any medical condition that, in the opinion of the investigator, may compromise compliance with the objectives and / or procedures of this protocol or preclude the administration of Botulinum Toxin.
• Changes in the treatment regimen of any drug that directly or indirectly interferes with neuromuscular function within 4 weeks before the start of the study treatment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: patients with spastic lower limb paresis; patients with spastic lower limb paresis secondary to Multiple Sclerosis	Drug: Botulinum toxin type A infiltrations; Echo-guided infiltration of botulinum toxin type A (Dysport®) in the lower limbs according to normal service practice

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effectiveness of repeated Botulinum Toxin infiltrations using objective results obtained by the clinician (Six Minutes Walking Test - 6MWT).	To assess the effectiveness of repeated Botulinum Toxin infiltrations on gait in patients with Multiple Sclerosis who presented limb spasticity less than 4 weeks after infiltration and its maintenance over time at 12 months, using objective results obtained by the clinician (Six Minutes Walking Test - 6MWT). Higher scores mean a better outcome.	12 months
Effectiveness of repeated Botulinum Toxin infiltrations using results reported by the patient (Twelve item Multiple Sclerosis Walking Scale - MSWS-12).	To assess the effectiveness of repeated Botulinum Toxin infiltrations on gait in patients with Multiple Sclerosis who presented limb spasticity less than 4 weeks after infiltration and its maintenance over time at 12 months, using results reported by the patient (Twelve item Multiple Sclerosis Walking Scale - MSWS-12). Higher scores mean a worse outcome.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of spasticity using Modified Ashworth Spasticity scale (MAS scale).	Evaluation of spasticity using Modified Ashworth Spasticity scale (MAS scale). Higher scores mean a worse outcome.	12 months
Evaluation of disability using Expanded Disability Status Scale de Kurtzke (EDSS scale).	Evaluation of disability using Expanded Disability Status Scale de Kurtzke (EDSS scale). Higher scores mean a worse outcome.	12 months
Evaluation of the quality of life after the use of botulinum toxin type A using Multiple Sclerosis Quality of Life 54 (MSQoL-54).	Evaluation of the quality of life after the use of botulinum toxin type A using Multiple Sclerosis Quality of Life 54 (MSQoL-54). Higher scores mean a better outcome.	12 months
Assessment of medium and long-term objectives using Goal Attainment Scaling (GAS scale).	Assessment of medium and long-term objectives using Goal Attainment Scaling (GAS scale). Higher scores mean a better outcome.	12 months
Number of adverse events.	Number of adverse events.	12 months

Collaborators and Investigators

• Sponsor: Aránzazu Vázquez Doce

Study record dates

Study Major Dates

• Study Start (Actual): January 24, 2019
• Primary Completion (Actual): July 28, 2022
• Study Completion (Actual): July 28, 2022

Study Registration Dates

• First Submitted: September 9, 2020
• First Submitted That Met QC Criteria: October 14, 2020
• First Posted (Actual): October 20, 2020

Study Record Updates

• Last Update Posted (Actual): August 9, 2022
• Last Update Submitted That Met QC Criteria: August 8, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: Multiple sclerosis; Botulinum toxin type A
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Neurologic Manifestations; Multiple Sclerosis; Sclerosis; Paresis; 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: LINITOX

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.: No