Outcome measures in a cohort of ambulatory adults with spinal muscular atrophy.

Introduction: With the advent of disease-altering therapies for spinal muscular atrophy (SMA), there is a requirement to better characterize outcome measures, particularly in milder forms of disease.

Methods: Maximal voluntary isometric contraction testing and 6-minute walk test (6MWT) performed in ambulatory SMA adults as part of the SMA-VALIANT trial were analyzed. Test-retest reliability and correlation with other candidate biomarkers and outcomes were investigated.

Dissemination and continuous improvement of a CTSA-based software platform, SPARCRequest, using an open source governance model.

SPARCRequest© (Services, Pricing, & Application for Research Centers) is a web-based research management system that provides a modular and adaptable "electronic storefront" for research-related services. Developed by the South Carolina Clinical & Translational Research Institute at the Medical University of South Carolina, it was released as open source (OS) code in 2014. The adoption of SPARCRequest© accelerated in 2016, when, to ensure responsiveness to the needs of partners, its governance also became open.

Clinical trial of L-Carnitine and valproic acid in spinal muscular atrophy type I.

Introduction: The aim of this study was to determine the safety and therapeutic potential of L-carnitine and valproic acid (VPA) in infants with spinal muscular atrophy (SMA).

Methods: Our investigation was an open-label phase 2 multicenter trial of L-carnitine and VPA in infants with SMA type I with retrospective comparison to an untreated, matched cohort. Primary outcomes were: safety and adverse events; secondary outcomes were survival, time to death/>16 hours/day of ventilator support; motor outcomes; and maximum ulnar compound motor action potential amplitude.

Nutritional practices at a glance: spinal muscular atrophy type I nutrition survey findings.

Proactive nutritional management for children with spinal muscular atrophy type I can provide insight into improved spinal muscular atrophy care. This observational study consisted of a nutritional and medical history survey of children with spinal muscular atrophy type I collected in 2009-2011. Forty-four caregiver survey responses were evaluated using descriptive statistics.

SMA valiant trial: a prospective, double-blind, placebo-controlled trial of valproic acid in ambulatory adults with spinal muscular atrophy.

Introduction: An open-label trial suggested that valproic acid (VPA) improved strength in adults with spinal muscular atrophy (SMA). We report a 12-month, double-blind, cross-over study of VPA in ambulatory SMA adults.

Methods: There were 33 subjects, aged 20–55 years, included in this investigation.

SMA CARNIVAL TRIAL PART II: a prospective, single-armed trial of L-carnitine and valproic acid in ambulatory children with spinal muscular atrophy.

Background: Multiple lines of evidence have suggested that valproic acid (VPA) might benefit patients with spinal muscular atrophy (SMA). The SMA CARNIVAL TRIAL was a two part prospective trial to evaluate oral VPA and L-carnitine in SMA children. Part 1 targeted non-ambulatory children ages 2-8 in a 12 month cross over design.

SMA CARNI-VAL trial part I: double-blind, randomized, placebo-controlled trial of L-carnitine and valproic acid in spinal muscular atrophy.

Background: Valproic acid (VPA) has demonstrated potential as a therapeutic candidate for spinal muscular atrophy (SMA) in vitro and in vivo.

Methods: Two cohorts of subjects were enrolled in the SMA CARNIVAL TRIAL, a non-ambulatory group of "sitters" (cohort 1) and an ambulatory group of "walkers" (cohort 2). Here, we present results for cohort 1: a multicenter phase II randomized double-blind intention-to-treat protocol in non-ambulatory SMA subjects 2-8 years of age.

Phase II open label study of valproic acid in spinal muscular atrophy.

Unlabelled: Preliminary in vitro and in vivo studies with valproic acid (VPA) in cell lines and patients with spinal muscular atrophy (SMA) demonstrate increased expression of SMN, supporting the possibility of therapeutic benefit. We performed an open label trial of VPA in 42 subjects with SMA to assess safety and explore potential outcome measures to help guide design of future controlled clinical trials. Subjects included 2 SMA type I ages 2-3 years, 29 SMA type II ages 2-14 years and 11 type III ages 2-31 years, recruited from a natural history study.

The Pediatric Randomized Carvedilol Trial in Children with Heart Failure: rationale and design.

Background: Carvedilol is a medication with both beta-receptor and alpha-receptor blocking properties that has been approved for the treatment of heart failure in adults. Little is known about its safety, efficacy, pharmacokinetics, and dosing profile in children.

Methods: The primary objective of this study is to evaluate the efficacy of carvedilol administered twice daily for 8 months in terms of its effect compared with placebo on a composite measure of clinical outcomes in children with symptomatic systemic ventricular systolic dysfunction and heart failure.