Valproate and Levocarnitine in Children With Spinal Muscular Atrophy

What Was Tested

This registered phase 3 trial tested L-Carnitine.

Spinal muscular atrophy (SMA), an autosomal recessive disorder, is characterized by muscle weakness due to degeneration of anterior horn cells in the spinal cord and brain stem nuclei.

It has a variable incidence of 1 in 6700 to 1 in 25000 live births and prevalence of 0.12 to 25 per 10,000 populations in different geographic areas and genetic constitution.

It had two arms (groups): Valproate, levocarnitine (active comparator) and Placebo (placebo comparator).

The patients will be randomized into two groups: Group I (Physiotherapy + Placebos) Group II (Physiotherapy + Valproate and Levocarnitine).

All patients will be randomized into two groups: Group I (Physiotherapy + Placebos) Group II (Physiotherapy + Valproate and Levocarnitine).

The registry classes the interventions as drug.

More on the Plan

Spinal muscular atrophy is an autosomal recessive disease of varying severity that destroys motor neurons, resulting in atrophy and weakness of the voluntary muscles.

Although the pathogenesis of the spinal muscular atrophy remains speculative, several hypotheses include defective inhibition of apoptosis, glutamate excitotoxicity and lack of a neurotrophic factor(s) in nerve or muscle.

The molecular genetic basis of spinal muscular atrophy (SMA), an autosomal recessive neuromuscular disorder, is the loss of function of the survival motor neuron gene (SMN1).

Drugs such as valproic acid, phenylbutyrate, and sodium butyrate that mainly act as histone deacetylase inhibitors can mediate both: they stimulate the SMN2 gene transcription and/or restore the splicing pattern, thereby elevating the levels of FL-SMN2 protein.

Who Took Part

60 planned participants were the target.

It was open to people of any sex aged from 2 years up to 15 years.

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

Examples of who could join: Children aged 2-15 years having motor weakness, hypotonia and hyporeflexia with onset noticed after 6 months of age.

The full record lists 2 inclusion and 6 exclusion criteria; among the exclusions: SMA type I, onset before 6 months of age; severely ill and unstable patients requiring life support system; other causes like cerebral palsy, down syndrome, connective tissue disorders, metabolic disorders.

How the Study Was Run

It was run as a randomized, parallel-group and quadruple-blind study.

The participants were allocated by chance, so the L-Carnitine group and the comparison group should start out alike.

The L-Carnitine group and the comparison group ran side by side rather than switching.

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 2013-08 with completion listed for 2016-12.

It ran at 1 site in India.

Its stated primary purpose is treatment.

What Was Measured

Primary outcome: Change in muscle power on a 5 point scale as per the principles of manual muscle testing at 12, 24, 36 and 52 weeks (time frame: Over 52 weeks with assessment at baseline, 12, 24, 36 and 52 weeks).

What This Means in Plain Language

Put simply, this is a phase 3, randomized trial of L-Carnitine in 60 people.

Its status is unknown; no results are posted to the registry yet, so nothing here describes outcomes.

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