Clinical Trial: Valproic Acid and Carnitine in Patients With Spinal Muscular Atrophy

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Multi-center Phase II Trial of Valproic Acid and Carnitine in Patients With Spinal Muscular Atrophy (SMA CARNI-VAL Trial)

Brief 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.

Detailed Summary: 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.
Sponsor: University of Utah

Current Primary Outcome:

• Safety Labs [ Time Frame: -4 wks, 0, 2 wks, 3 mo, 6 mo, 9 mo, 12 mo for safety labs; throughout for AEs ]
  Participants will have labs drawn regularly to maintain appropriate dosing and monitor liver function
• Efficacy, Measured Through Motor Function Assessments [ Time Frame: -4wks, 0, 3 mo, 6 mo, 12 mo ]
• Modified Hammersmith Change From Baseline to 6 Months [ Time Frame: 0 months, 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.

Original Primary Outcome:

• Cohort 1:
• 1.Safety
• 2.Functional Status/Strength as assessed via Modified Hammersmith Functional Motor Scale (MHFMS)
• Cohort 2:
• 1.Safety labs:
• 2.Project Cure Functional Motor Scale for SMA
• 3.Myometry > 5 yrs (CITEC) right-sided grip, elbow flexion, knee extension

Current Secondary Outcome:

• 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) [ Time Frame: 1 month prior to official enrollment, beginning of study (0 months), 6 months, 12 months (data point not available) ]
  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.
• Max CMAP Amplitude Median [ Time Frame: 1 month prior to official enrollment, beginning of study (0 months), 6 months, 12 months (data point not available) ]
  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.
• 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) [ Time Frame: 1 month prior to official enrollment, beginning of study (0 months), 6 months, 12 months (data point not available) ]
  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.
• Max CMAP Area (Median) [ Time Frame: 1 month prior to official enrollment, beginning of study (0 months), 6 months, 12 months (data point not available) ]
  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.

Original Secondary Outcome:

• Cohorts 1 & 2
• 1.Pulmonary Function Testing:
• 2.Quantitative assessment of SMN mRNA from blood samples
• 3.Peds QL™ assessment: parental version (all), child versions (> 5yrs)
• 4.Max CMAP amplitude/area
• 5.Ulnar MUNE
• 6.Growth and vital sign parameters
• 7.Nutritional Status

Dates:
Date Received: September 23, 2005
Date Started: September 2005
Date Completion:
Last Updated: September 22, 2011
Last Verified: September 2011