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

Study Overview
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Brief Summary
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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).

Detailed Description
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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.

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

Conditions
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Spinal Muscular Atrophy Type 3

Intervention / Treatment
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* Drug: Pyridostigmine Bromide


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 6 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: significant decrement<br>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<br> <br> * Other names: Mestinon;|
| No Intervention: no decrement<br>Patient without significant decrement will not receive any treatment and will be the control group | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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electromyography, spinal muscular atrophy type 3, fatigability, decrement