Phase 2
N=94
Valproic Acid and Carnitine in Patients With Spinal Muscular Atrophy
Spinal Muscular Atrophy
Bottom Line
View on ClinicalTrials.gov: NCT00227266 ↗Enrolled (actual)
94
Serious AEs
9.6%
Results posted
May 2011
Primary outcome: Primary: Safety Labs
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Valproic Acid and Levocarnitine (Drug); Placebo (Drug)
- Age
- Pediatric · 2+ yrs
- Sex
- All
- Sponsor
- University of Utah
- Primary completion
- Nov 2007
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Safety Labs |
— | — |
| PRIMARY Efficacy, Measured Through Motor Function Assessments |
— | — |
| PRIMARY Modified Hammersmith Change From Baseline to 6 Months |
20.0; 16.6; 20.6; 16.8; 0.6; 0.2 | — |
| SECONDARY Quantitative Assessment of SMN mRNA From Blood Samples |
— | — |
| SECONDARY Peds QL™ Assessment: Parental Version (All), Child Versions (> 5yrs) |
— | — |
| SECONDARY Max CMAP Amplitude (Mean) |
2.28; 2.93; 5.52; 2.32; 2.37; 6.56 | — |
| SECONDARY Max CMAP Amplitude Median |
1.91; 2.2; 5.3; 1.44; 1.8; 5.85 | — |
| SECONDARY Ulnar MUNE |
— | — |
| SECONDARY Growth and Vital Sign Parameters |
— | — |
| SECONDARY Nutritional Status |
— | — |
| SECONDARY DEXA |
— | — |
| SECONDARY Max CMAP Area (Mean) |
5.46; 5.45; 14.85; 5.28; 5.26; 16.26 | — |
| SECONDARY Max CMAP Area (Median) |
3.6; 4.6; 13.65; 3.74; 3.4; 16.85 | — |
Summary
This is a multi-center trial to assess safety and efficacy of a combined regimen of oral valproic acid (VPA) and carnitine in patients with Spinal Muscular Atrophy (SMA) 2 to 17 years of age. Cohort 1 is a double-blind placebo-controlled randomized intention to treat protocol for SMA "sitters" 2 - 8 years of age. Cohort 2 is an open label protocol for SMA "standers and walkers" 3 - 17 years of age to explore responsiveness of efficacy outcomes. Outcome measures will include blood chemistries, functional testing, pulmonary function testing, electrophysiological evaluations, PedsQL quality of life assessment, quantitative assessments of survival motor neuron (SMN) mRNA from blood samples, growth and vital sign parameters. Six centers will enroll a total of 90 patients.
Eligibility Criteria
Inclusion Criteria
Cohort 1
- Confirmed genetic diagnosis of 5q SMA
- SMA 2 or non-ambulatory SMA 3: all subjects must be able to sit independently for at least 3 seconds without support
- Age 2 to 8 years at time of enrollment
Cohort 2
- Confirmed genetic diagnosis of 5q SMA
- SMA subjects (SMA types 2 or 3) who can stand independently without braces or other support for up to 2 seconds, or walk independently
- Age 3 to 17 years at time of study enrollment
Exclusion Criteria
Cohort 1
- Need for BiPAP support > 12 hours per day
- Spinal rod or fixation for scoliosis or anticipated need within six months of enrollment
- Inability to meet study visit requirements or cooperate reliably with functional testing
- Coexisting medical conditions that contraindicate travel, testing or study medications
- Use of medications or supplements which interfere with valproic acid or carnitine metabolism within 3 months of study enrollment.
- Current use of either VPA or carnitine. If study subject is taking VPA or carnitine then patient must go through a washout period of 12 weeks before enrollment into the study
- Body Mass Index > 90th % for age
Cohort 2
- Spinal rod or fixation for scoliosis or anticipated need within six months of enrollment
- Inability to meet study visit requirements or cooperate with functional testing
- Transaminases, amylase or lipase > 3.0 x normal values, WBC 90th % for age
- Pregnant women/girls, or those intending to try to become pregnant during the course of the study.
Data sourced from ClinicalTrials.gov (NCT00227266). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.