Study of Safety and Dosing Effect on SMN Levels of Valproic Acid (VPA) in Patients With Spinal Muscular Atrophy

Study Overview
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Brief Summary
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This is an open label phase I/II clinical trial to assess safety, tolerability and potential effect on SMN mRNA and protein in vivo of a compound in which preliminary evidence supports a potential effect on SMN levels in vitro.

Detailed Description
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This is an open label phase I/II trial of valproic acid in 40 SMA subjects > 2 years of age with severe, intermediate, and mild phenotypes. Primary outcome measures includes laboratory and physical examination assessments to monitor effects on liver, hematologic, metabolic and nutritional status. Secondary outcomes includes measures of gross motor function; electrophysiologic measures of denervation; DEXA estimates of body composition, bone mineral density and content; measures of pulmonary function; and quantitative SMN mRNA and protein levels in blood cells. Subjects will need 2-3 baseline visits over a 3 -6 month period prior to enrollment. Follow-up visits will be scheduled at 3, 6 and 12 months on treatment.

Official Title
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In Vivo Study of Safety, Tolerability and Dosing Effect on SMN mRNA and Protein Levels of Valproic Acid in Patients With Spinal Muscular Atrophy

Conditions
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Spinal Muscular Atrophy

Intervention / Treatment
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* Drug: Valproic Acid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have a diagnosis of SMA, confirmed by genetic testing Only patients 2 years of age and older at enrollment will be eligible Exclusion Criteria: Patients taking any medications with known hepatotoxicity, congenital metabolic disorders or on multiple anticonvulsant medications Patients taking medications which may interact with VPA Patients on ventilatory support for more than 16 hours per day Patients currently enrolled in other treatment trials

Ages Eligible for Study
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Minimum Age: 2 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: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Valproic Acid|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess safety and tolerability of VPA in SMA patients greater than 2 years of age |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To look for a potential in vivo effect of VPA on SMN mRNA in patient blood cells at routinely used clinical doses |  |  | 
| Measures of gross motor function |  |  | 
| Electrophysiologic measures of denervation |  |  | 
| DEXA estimates of body composition, bone mineral density and content |  |  | 
| Measures of pulmonary function |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Spinal Muscular Atrophy (SMA), Valproic Acid