Valproic Acid and Carnitine in Patients With Spinal Muscular Atrophy

What Was Tested

In this phase 2 trial, researchers set out to test L-Carnitine.

Cohort 1 is a double-blind placebo-controlled randomized intention to treat protocol for SMA "sitters" 2 - 8 years of age.

It had three arms (groups): Cohort 1a (placebo comparator), Cohort 1b (active comparator) and Cohort 2 (experimental).

The registry classes the interventions as drug.

More on the Plan

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.

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.

Who Took Part

Enrollment: 94 actual participants took part.

It was open to people of any sex aged from 2 years up to 17 years.

Healthy volunteers were not accepted; participants needed the condition being studied.

Examples of who could join: 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. 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.

The full record lists 6 inclusion and 15 exclusion criteria; among the exclusions: need for bipap support \> 12 hours per day; inability to meet study visit requirements or cooperate reliably with functional testing; coexisting medical conditions that contraindicate travel, testing or study medications.

How the Study Was Run

Design: randomized, crossover and quadruple-blind.

Because people in this L-Carnitine study were split into groups at random, differences between the groups are less likely to reflect who happened to join each one.

In the crossover set-up each of the participants took both L-Carnitine and the comparison in turn, acting as their own control.

Neither the participants nor the staff measuring them knew who was on L-Carnitine, so expectations could not easily colour the readings.

Those kept unaware of assignments: participant, care provider, investigator and outcomes assessor.

It started in 2005-09 with completion listed for 2007-11.

It ran at 6 sites in United States (5) and Canada (1).

Its stated primary purpose is treatment.

What Was Measured

Researchers chose this as the main measure: Safety Labs (time frame: -4 wks, 0, 2 wks, 3 mo, 6 mo, 9 mo, 12 mo for safety labs; throughout for AEs). Modified Hammersmith Change From Baseline to 6 Months (time frame: 0 months, 6 months).

It also tracked 10 secondary outcomes, for example Quantitative Assessment of SMN mRNA From Blood Samples, Peds QL™ Assessment: Parental Version (All), Child Versions (> 5yrs), Max CMAP Amplitude (Mean), Max CMAP Amplitude Median, Ulnar MUNE and Growth and Vital Sign Parameters.

What This Means in Plain Language

Put simply, this is a phase 2, randomized trial of L-Carnitine in 94 people.

The trial is marked completed; results are posted on the registry, and this page does not restate them.

More context: the L-Carnitine compound page, all human trials.