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

Phase 1

Completed

• Conditions: Spinal Muscular Atrophy

• Registration Number: NCT00374075
• Lead Sponsor: University of Utah

Brief Summary

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

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.

Study Timeline

• Study Start: 2003-09
• Study Completion: 2006-02
• Study First Submitted: 2006-09-06
• Study First Submitted QC: 2006-09-06
• Study First Posted: 2006-09-08
• Status Verified: 2016-08
• Last Update Submitted: 2023-05-08
• Last Update Posted: 2023-05-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 42

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
To assess safety and tolerability of VPA in SMA patients greater than 2 years of age

Secondary Outcome Measures

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

Trial Locations

Locations (1)

University of Utah/Primary Children's Medical Center; 🇺🇸 Salt Lake City, Utah, United States