Efficacy, safety and tolerability of high lipid supplementation in amyotrophic lateral sclerosis
Final Report Abstract
In animal models and in humans with PEG, existing literature suggests that hypercaloric, fatrich nutrition prolongs life. It was the purpose of this study to investigate, whether or not a fatrich diet prolongs life of patients with ALS. Patients with diagnosis of possible, probable or definite ALS were included in this randomized, multicenter, placebo-controlled, double-blind, prospective clinical study. Eligible patients were randomly assigned (1:1) to receive either a high caloric fatty diet (45 g fat, 405 kcal; HCFD) or a matching placebo supplement in addition to standard care (riluzole 100 mg/day). Patients were followed up 3, 6, 9, 12, 15, and 18 months after randomization. The primary endpoint was survival time, secondary efficacy outcomes were change of total score of ALS-FRS-R, change of slow vital capacity (SVC), and change in individual quality of life using the Schedule for the Evaluation of the Individual Quality of Life (SEIQoL), time to tracheostomy or death (combined), change of Body Mass index (BMI), and change of appetite-score (Council of Nutrition Appetite Questionnaire (CNAQ)). 207 patients were enrolled and randomly assigned to receive either placebo (104) or HCFD (n=103) after stratification based on site of onset (bulbar or spinal) and BMI (>21.75 kg/m 2 vs. ≤21.75 kg/m2). Measurement of the primary outcome survival showed no significant effect after 18 months (p= 0.21); in the subgroup of fast progressors, which constitutes 50 % of the entire study population, the therapeutic effect was convincingly positive (p=0.02). In line with this observation, target engagement could be shown in this group since weight loss was significantly reduced compared to placebo. Consistently, we also found a convincing effect on disease progression as measured by loss of ALS-FRS-R score per month, which was slowed down significantly in the HCFD group compared to placebo (ITT population). We could show in the ITT analysis that a high caloric fatty diet slowed down disease progression in ALS patients compared to control group. Moreover, half of the patient group, the fast progressors, also had a significant survival benefit (p=0.02). Consistently, this benefit was related to the effect on body weight, which was stabilized in the HCFD group compared to placebo. Although dose-response relationships need to be defined in further studies, this study shows that therapeutic interventions targeting metabolism are promising for ALS and possibly other diseases associated with catabolism, such as Huntington´s disease, Frontotemporal Dementia, and even catabolism associated with old age.
