Valproic Acid and Carnitine in Patients With Spinal Muscular Atrophy
Condition: Spinal Muscular Atrophy
MeSH terms: Muscular Atrophy; Muscular Atrophy, Spinal; Atrophy
Intervention: Valproic Acid and Levocarnitine; Placebo
Intervention description: VPA,sprinkle cap; Levocarnitine, syrup; dosage is by weight
Intervention MeSH terms: Valproic Acid
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 94.0
Sex: All
Minimum age: 2 Years
Maximum age: 17 Years
Healthy volunteers: No
Keywords: Spinal Muscular Atrophy (SMA); SMA Type 2; SMA Type 3

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 < 3.0 or neutropenia <
             1.0, platelets < 100 K, or hematocrit < 30 persisting over a 30 day period.

          -  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 be go through a washout period of 12 weeks before enrollment in the
             study.

          -  Body Mass Index > 90th % for age

          -  Pregnant women/girls, or those intending to try to become pregnant during the course
             of the study.