Swoboda 2010.

Methods	Randomised, placebo‐controlled, double‐blind trial
Participants	61 non‐ambulatory participants with SMA types II or III Inclusion criteria: confirmed genetic diagnosis of 5q SMA SMA 2 or non‐ambulatory SMA 3: SMA 2 participants must have been able to sit independently for ≥ 3 seconds without support aged 2–8 years at time of enrolment Exclusion criteria: MHFMS for children with SMA (MHFMS‐SMA) total score ≤ 2 or ≥ 37 need for bilevel positive airway pressure support > 12 hours per day spinal rod or fixation for scoliosis or anticipated need within 6 months of enrolment inability to meet study visit requirements or co‐operate reliably with functional testing presence of predefined biochemical or haematological abnormalities in blood work co‐existing medical conditions that contraindicate travel, testing or study medications use of medications or supplements which interfere with valproic acid or carnitine metabolism, increase the potential risks of these medications or were hypothesised to have a beneficial effect in SMA animal models or human neuromuscular disorders within 3 months of study enrolment (specifically, concomitant use of riluzole, creatine, butyrate derivatives, growth hormone, anabolic steroids, daily albuterol use, anticonvulsants or other histone deacetylase inhibitors would preclude enrolment) current use of either valproic acid or carnitine through participation in another study or been prescribed by their attending physician (if study participant is taking valproic acid or carnitine then participant must have gone through a washout period of 12 weeks before been enrolled into the study) body mass index ≥ 90th percentile for age
Interventions	Oral liquid carnitine 50 mg/kg/day in 2 doses in combination with oral valproic acid capsules in 2–3 doses to maintain overnight serum level trough 50–100 mg/dL or liquid placebo twice daily in combination with placebo capsule 2–3 times a day Duration of treatment: 12 months in active treatment and 6 months in placebo group. The placebo group switched to active treatment after 6 months per protocol Total follow‐up: 12 months
Outcomes	Primary: safety, motor function assessments, change in functional score (MHFMS) Secondary: include change in quality of life (PedsQL), change in innervation via maximum ulnar CMAP, adverse events. Change in muscle strength and change in pulmonary function were measured in participants aged ≥ 5 years
Funding	Quote: "Abbott Pharmaceutical provided VPA [valproic acid] and placebo, and Sigma‐Tau Pharmaceutical provided L‐carnitine, at no cost."
Conflicts of interest	Quote: "The authors have declared that no competing interests exist."
Notes	Baseline differences in body mass index and gender between the different treatment groups.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomly assigned using a permuted block design balancing for institution.
Allocation concealment (selection bias)	Low risk	Randomisation was performed using a permuted block design balancing for institution. Randomisation was performed centrally by telephone.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Blinding of participants and key study personnel. Medical monitor was unblinded.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Blinding of participants and key study personnel. Medical monitor was unblinded.
Incomplete outcome data (attrition bias) All outcomes	High risk	Not all outcome measures are available for analysis. Missing data were not fully explained.
Selective reporting (reporting bias)	Low risk	Protocol available. There was clear evidence that reported results correspond to all intended outcome measurements.
Other bias	Unclear risk	Partial cross‐over design after 6 months.