Safety and Efficacy Study of Pyridostigmine on Patients With Spinal Muscular Atrophy Type 3 (EMOTAS)

Safety and Efficacy Study of Anti-cholinesterase Therapy on the Motor Functions in Patients With Spinal Muscular Atrophy Type 3.

The purpose of this study is to evaluate safety and efficacy of anti-cholinesterase therapy on the motor function in SMA type 3 patients with impaired neuromuscular junction (NMJ).

Study Overview

• Status: Completed
• Conditions: Spinal Muscular Atrophy Type 3
• Intervention / Treatment: Drug: Pyridostigmine Bromide

Detailed Description

Spinal muscular atrophy (SMA) is the second neuromuscular disease meet in children. SMA is a genetically transmitted disease inducing muscular weakness predominating on shoulders and hips. Currently, there is no effective therapy to slow the progression of the disease. SMA is due to a neuron motor attempt of the spinal cord and recently it has been demonstrated a neuromuscular junction (NMJ) involvement, according to recent studies.

EMOTAS study aim to understand if NMJ abnormalities could have an impact on motor performance and fatigue in SMA type 3 ambulatory patients by electromyogram and to improve by non-invasive therapy quality of life of patients.

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Liège, Belgium, 4000
    • Centre de référence des maladies neuromusculaire, Centre Hospitalier Régional de la Citadelle

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Spinal muscular atrophy type 3, genetically confirmed

  • Age higher than 6 years old
  • Ambulatory patient
  • Informed consent signed
  • More than 100 meters of walking at 6-minute walk test at screening
  • Value at screening and baseline in a range of 20% of the highest value at 6-minute walk test

Exclusion Criteria:

• Patient who had surgical intervention or suffer from a recent traumatism (less than 6 months)

  • Associated pathology such as endocrinopathy, infectious disease, allergy, myopathy, chronic or acute inflammatory pathology, during 3 weeks preceding the inclusion.
  • Other therapeutics than food supplements or those frequently prescribed in spinal muscular atrophy or its complications
  • Non tolerance of electromyography
  • Limited collaboration due to trouble in information comprehension
  • Pathology inducing contra-indication for pyridostigmine treatment (allergy at molecule, asthma, Parkinson disease, mechanic obstruction of urinary or digestive tracts)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: significant decrement; Patients with significant decrement at electromyogram will be treated by pyridostigmine bromide 60mg 3 times a day for patients older than 18 and 1.5mg/kg 3 times a day for children less than 40kg	Drug: Pyridostigmine Bromide; Other Names: Mestinon
No Intervention: no decrement; Patient without significant decrement will not receive any treatment and will be the control group

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change from Baseline in the distance walked at 6-minute walk test at 6 months	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline of decrement at 6 months		6 months
Change from baseline of MFM-D1	Comparison of treated and control group values will be made	6 months
Change from baseline of Moviplate values at 6 months	Comparison between treated and control group value will be made	6 months
Change from baseline of the ratio at 6 minutes walk test at 6 months	It's the ratio between the number of meters during the last minute of the 6-minute walk test and the first minute of the 6-minute walk test.	6 months

Collaborators and Investigators

• Sponsor: Centre Hospitalier Régional de la Citadelle
• Investigators: Principal Investigator: Stephanie Delstanche, Centre de référence des maladies neuromusculaire de Liège

Study record dates

Study Major Dates

• Study Start: July 1, 2014
• Primary Completion (Actual): July 1, 2017
• Study Completion (Actual): July 1, 2017

Study Registration Dates

• First Submitted: August 20, 2014
• First Submitted That Met QC Criteria: August 26, 2014
• First Posted (Estimated): August 28, 2014

Study Record Updates

• Last Update Posted (Actual): October 11, 2023
• Last Update Submitted That Met QC Criteria: October 9, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: electromyography; fatigability; spinal muscular atrophy type 3; decrement
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Genetic Diseases, Inborn; Neuromuscular Diseases; Neurodegenerative Diseases; Neuromuscular Manifestations; Pathological Conditions, Anatomical; Spinal Cord Diseases; Heredodegenerative Disorders, Nervous System; Motor Neuron Disease; Muscular Atrophy; Atrophy; Muscular Atrophy, Spinal; Spinal Muscular Atrophies of Childhood; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Enzyme Inhibitors; Anticonvulsants; Cholinesterase Inhibitors; Bromides; Pyridostigmine Bromide
• Other Study ID Numbers: 1376