Spinal Muscular Atrophy Type I in infants MedDRA version: 9.1 Level: LLT Classification code 10051203 Term: Spinal muscular atrophy congenital
Conditions
Interventions
Trade Name: Orfiril Saft
Pharmaceutical Form: Oral solution
INN or Proposed INN: VALPROATE SODIUM
CAS Number: 1069665
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concen
Sponsors
University of Utah
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Laboratory documentation of SMN mutation or deletion consistent with genetic diagnosis of SMA • Clinical diagnosis of SMA type I • Age between 2 weeks and 12 months • Written informed consent of parent/guardian Are the trial subjects under 18? yes Number of subjects for this age range: F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: • Any clinical or laboratory evidence of hepatic or pancreatic insufficiency. • Laboratory results drawn within 14 days prior to start of study drug demonstrating: - Liver transaminases (AST, ALT), lipase, amylase: >1.5 x ULN, - White Blood Cell Count: < 3 x 10^9/l - Neutropenia: <1 x 10^9/l - Platelet: <100 x 10^9/l - Hematocrit: <30 %, persisting over a 30-day period • Serious illness requiring systemic treatment and/or hospitalization within two weeks prior to study entry. • Use of medications or supplements within 30 days of study enrollment that - interfere with VPA or carnitine metabolism - that increase the potential risks of VPA or carnitine - that are hypothesized to have a beneficial effect in SMA animal models or human neuromuscular disorders, including riluzole, valproic acid, hydroxyurea, oral use of albuterol, sodiumphenylbutyrate, butyrate derivatives, creatinine, growth hormone, anabolic steroids, probenecid, oral or parenteral use of corticosteroids at entry, or agents anticipated to increase or decrease muscle strength or agents with presumed histone deacetylase (HDAC) inhibition • Infants who have participated in a treatment trial for SMA within 30 days of study entry or who will become enrollees in any other treatment trial during the course of this study. • Unwillingness to travel for study assessments. • Coexisting medical conditions that contradict use of VPA/carnitine or travel to and from study site. • Requirement of ventilator support for more than 12 hours per day.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: • Time to death or dependence upon >16 hours/day (24 hours) ventilatory support • To evaluate motor function using the Test of Infant Motor Performance Screening Inventory (TIMPSI). • To validate a newly developed tool, the Project Cure Functional Rating Scale for SMA Type I: A Caregiver Questionnaire (PCFRS-I), which documents functional status and quality of life of the child and quality of life of the primary caregiver. • To determine motor-neuron loss at baseline and 6 months post treatment as assessed using maximum Compound Muscle Action Potential (CMAP) and Motor Unit Number Estimation (MUNE) values (a measure of denervation). • To conduct genetic and biochemical assays to determine SMN2 copy number, quantitative SMN mRNA levels, and HDAC-inhibition. • To determine a possible effect of VPA/carnitine on bone density using DEXA.;Primary end point(s): • safety following 6 months of treatment • time to death/ventilator dependence >16 hours per day will be compared to age and gender-matched SMA type I historical controls;Main Objective: • to obtain additional safety parameters for use of VPA/carnitine in SMA type I infants • to validate methods of estimating overall nutritional status in SMA type I infants with sarcopenia and to correlate such measures with motor function and time to death/dependence upon >16 hours/day (24 hours) ventilatory support | — |
Countries
Germany
Outcome results
None listed