Hypercaloric enteral nutrition in Amyotrophic Lateral Sclerosis : a randomized double-blind placebo-controlled trial

Background—Amyotrophic Lateral Sclerosis (ALS) is a rapidly fatal neurodegenerative disease with few therapeutic options. Mild obesity is associated with greater survival in ALS patients and calorie-dense diets increase survival in an ALS mouse model. We therefore hypothesized that hypercaloric diets might lead to weight gain and slow ALS disease progression. Methods—In this double-blind, placebo-controlled, multi-center clinical trial, we enrolled adults with ALS without a history of diabetes, significant liver or cardiovascular disease, who were already receiving percutaneous enteral nutrition. We randomly assigned participants to one of Wills et al. Page 2 Lancet. Author manuscript; available in PMC 2015 June 14. N IH -P A A uhor M anscript N IH -P A A uhor M anscript N IH -P A A uhor M anscript three dietary interventions: replacement calories using an isocaloric diet (controls) vs. a highcarbohydrate hypercaloric diet (HC/HC), vs. a high-fat hypercaloric diet (HF/HC). Participants received the intervention diets for four months and were followed for five months. The primary outcomes were safety and tolerability. Secondary outcomes included measures of disease progression, survival, and metabolism. This trial is registered with Clinicaltrials.gov, number NCT00983983. Findings—A total of 24 participants were enrolled of whom 20 initiated study diet (six control, eight HC/HC, six HF/HC). Baseline demographics were similar among the three study arms. The HC/HC diet was better tolerated with fewer serious adverse events than the control diet (zero vs. nine, p<0·001) and fewer dose discontinuations due to adverse events (0% vs. 50%). There were no deaths in the HC/HC arm vs. three deaths (43%) in the control arm (logrank p = 0·03). The HF/HC arm was not statistically different from the controls in adverse events, tolerability, deaths or disease progression. Interpretation—Our results suggest that hypercaloric enteral nutrition is safe and tolerable in ALS and support the study of nutritional interventions at earlier stages of the disease. Funding—The Muscular Dystrophy Association with additional support from the National Center for Research Resources, the National Institutes of Health, and the Harvard NeuroDiscovery Center.