Clinical trial NCT00374075: Study of Safety and Dosing Effect on SMN Levels of Valproic Acid (VPA) in Patients With Spinal Muscular Atrophy
Official title: In Vivo Study of Safety, Tolerability and Dosing Effect on SMN mRNA and Protein Levels of Valproic Acid in Patients With Spinal Muscular Atrophy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Spinal Muscular Atrophy
Keywords: Spinal Muscular Atrophy (SMA)
Valproic Acid
Lead sponsor: University of Utah
Sponsor class: OTHER
Collaborators: name: Families of Spinal Muscular Atrophy
name: Leadiant Biosciences, Inc.
name: Abbott
First posted: 2006-09-08
Enrollment: 42
Sex: ALL
Minimum age (years): 2
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: To assess safety and tolerability of VPA in SMA patients greater than 2 years of age
Secondary outcomes:
measure: To look for a potential in vivo effect of VPA on SMN mRNA in patient blood cells at routinely used clinical doses
measure: Measures of gross motor function
measure: Electrophysiologic measures of denervation
measure: DEXA estimates of body composition, bone mineral density and content
measure: Measures of pulmonary function
Other outcomes:
Locations:
city: Salt Lake City
country: United States
facility: University of Utah/Primary Children's Medical Center
state: Utah
Study officials:
affiliation: University of Utah/Primary Children's Medical Center
name: Kathryn J Swoboda, M.D
role: PRINCIPAL_INVESTIGATOR
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