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.
This is a multi-center phase II trial 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. Subjects will undergo two baseline assessments over 4 to 6 week period, then will be randomized to treatment or placebo for the next six months. All subjects will then be placed on active treatment for the subsequent six month period. Cohort 2 is an open label protocol for SMA "standers and walkers" 3 - 17 years of age to explore responsiveness of efficacy outcomes. Subjects will undergo two baseline assessments over a four to six week period, followed by one year active treatment with VPA and carnitine. Outcome measures are performed every 3 to 6 months, and 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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
94
VPA,sprinkle cap; Levocarnitine, syrup; dosage is by weight
Johns Hopkins University
Baltimore, Maryland, United States
Children's Hospital of Michigan
Detroit, Michigan, United States
Ohio State University
Columbus, Ohio, United States
University of Utah/Primary Children's Medical Center
Salt Lake City, Utah, United States
University of Wisconsin Children's Hospital
Madison, Wisconsin, United States
Hospital Sainte-Justine
Montreal, Quebec, Canada
Safety Labs
Participants will have labs drawn regularly to maintain appropriate dosing and monitor liver function
Time frame: -4 wks, 0, 2 wks, 3 mo, 6 mo, 9 mo, 12 mo for safety labs; throughout for AEs
Efficacy, Measured Through Motor Function Assessments
Time frame: -4wks, 0, 3 mo, 6 mo, 12 mo
Modified Hammersmith Change From Baseline to 6 Months
Comparison of Modified Hammersmith Change from baseline to 6 months. Scores range from 0 to 40. A higher score indicates a better outcome. This scale is used to assess gross motor abilities of non-ambulant children with SMA in multiple research trials as well as in clinical settings.
Time frame: 0 months, 6 months
Quantitative Assessment of SMN mRNA From Blood Samples
Time frame: -4wks or 0, 3 mo, 6 mo, 12 mo
Peds QL™ Assessment: Parental Version (All), Child Versions (> 5yrs)
Time frame: -4wks, 0, 3mo, 6mo, 12mo
Max CMAP Amplitude (Mean)
The maximum Compound Motor Action Potential (CMAP) is a measurement obtained through EMG testing that is associated with disease progression. In this study, we measure the maximum CMAP by stimulating one nerve in the hand and measuring the response of the muscle. This is done multiple times, the outcome used is the highest peak, or response observed.
Time frame: 1 month prior to official enrollment, beginning of study (0 months), 6 months, 12 months (data point not available)
Max CMAP Amplitude Median
The maximum Compound Motor Action Potential (CMAP) is a measurement obtained through EMG testing that is associated with disease progression. In this study, we measure the maximum CMAP by stimulating one nerve in the hand and measuring the response of the muscle. This is done multiple times, the outcome used is the highest peak, or response observed.
Time frame: 1 month prior to official enrollment, beginning of study (0 months), 6 months, 12 months (data point not available)
Ulnar MUNE
Time frame: -4 wks, 0, 3 mo, 6 mo, 12 mo
Growth and Vital Sign Parameters
Time frame: -4 wks, 0, 3mo, 6mo, 12mo
Nutritional Status
Time frame: -4 wks, 0, 3mo, 6mo, 12mo
DEXA
Time frame: 0, 6mo, 12mo
Max CMAP Area (Mean)
The maximum Compound Motor Action Potential (CMAP) area is a measurement obtained through EMG testing that is associated with disease progression. In this study, we measure the maximum CMAP by stimulating one nerve in the hand and measuring the response of the muscle. This procedure is repeated multiple times. The maximum area is the response that results in the largest area under the response curve.
Time frame: 1 month prior to official enrollment, beginning of study (0 months), 6 months, 12 months (data point not available)
Max CMAP Area (Median)
The maximum Compound Motor Action Potential (CMAP) area is a measurement obtained through EMG testing that is associated with disease progression. In this study, we measure the maximum CMAP by stimulating one nerve in the hand and measuring the response of the muscle. This procedure is repeated multiple times. The maximum area is the response that results in the largest area under the response curve.
Time frame: 1 month prior to official enrollment, beginning of study (0 months), 6 months, 12 months (data point not available)
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