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Recent publications showed that circulating neurofilaments (Nfs) may be used as a diagnostic biomarker distinguishing amyotrophic lateral sclerosis (ALS) from ALS mimics with high sensitivity and specificity.1–3 Furthermore, it has been shown that patients with higher Nf levels show faster disease progression1 and shorter survival.2 3 Nf levels remain rather stable during the course of disease.2 Current literature suggests that the diagnostic value of neurofilament light chains (NfL) and phosphorylated neurofilament heavy chains in cerebrospinal fluid is about equal, whereas in blood NfL seems to be superior.4 In this study, we investigated the effect of a high-caloric fatty diet (HCFD) on NfL serum levels, using blood samples collected during the LIPCAL-ALS (efficacy, safety and tolerability of high lipid and caloriesupplementation in amyotrophic lateral sclerosis) study, a randomised, double-blind, parallel-group, placebo-controlled, multicentre trial, which investigated the therapeutic effect of HCFD in ALS.5 In LIPCAL-ALS, 201 patients (80 women, 121 men, age 62.4±10.8) were randomly assigned (1:1) to receive either HCFD (405 kcal/day, 100% fat) or placebo in addition to riluzole (100 mg/day) for 18 months.
Although the primary outcome overall survival was negative in the whole study population (p=0.44), the post hoc analysis revealed a significantly longer survival for fast-progressing patients (ie, patients with an Amyotrophic Lateral Sclerosis Functional Rating Scale Revised (ALSFRS-R) slope >median between disease onset and baseline) in the HCFD group compared with placebo.5
To further corroborate our hypothesis of a disease-modifying effect of HCFD, we analysed NfL serum levels from LIPCAL-ALS participants.
At each on-site visit during LIPCAL-ALS (6-month intervals), patients were asked if they were willing to provide an additional serum sample for NfL analysis on a voluntary basis. Serum NfL concentrations were measured with the single molecule array (Simoa) platform provided by Quanterix (Lexington, Massachusetts, USA) with single measurements …
JD and JS contributed equally.
Collaborators LIPCAL-ALS Study Group.
Contributors JoD, ACL, JS, MO and JeD contributed to the conception and design of the study. ACL, JoD, JS, LD, JeD, JW, JK, UW, TM, SP, AH, BJ, JG, TG, DZ, MB, BS, JP, AW, SG and and FR contributed to the acquisition and analysis of data. JoD, ACL, JS, LD, MO, SW and JeD contributed to drafting the text and preparing the figures. For information about the Study Group members and affiliations, see supplementary material.
Funding The LIPCAL-ALS study was an investigator-initiated trial of the German ALS/MND network, with institutional support from the German Research Foundation (DFG, grant number LU 336/16-1). Nutricia GmbH (Erlangen, Germany) provided the dietary supplement at a cost reduction of 15%.
Competing interests ACL reports that the dietary supplement used in the LIPCAL-ALS study was provided at a cost reduction of 15% by Nutricia GmbH (Erlangen, Germany). All other authors have nothing to report.
Patient consent for publication Not required.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement Individual participant data that underlie the results reported in this article, after deidentification (text, tables and figures), as well as the study protocol will be available. Data will be available beginning 3 months and ending 5 years following article publication. Data will be shared with researchers who provide a methodologically sound proposal. Data will be shared for analyses to achieve the aims in the approved proposal. Proposals should be directed to firstname.lastname@example.org; to gain access, data requestors will need to sign a data access agreement. Data are available for 5 years at https://www.uniklinik-ulm.de/neurologie.html. JoD had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. JeD conducted and is responsible for the data analysis.