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Effect of high-caloric nutrition on serum neurofilament light chain levels in amyotrophic lateral sclerosis
  1. Johannes Dorst1,
  2. Joachim Schuster1,
  3. Jens Dreyhaupt2,
  4. Simon Witzel1,
  5. Jochen H Weishaupt1,
  6. Jan Kassubek1,
  7. Ulrike Weiland1,
  8. Susanne Petri3,
  9. Thomas Meyer4,
  10. Torsten Grehl5,
  11. Andreas Hermann6,7,
  12. Berit Jordan8,9,
  13. Julian Grosskreutz10,
  14. Daniel Zeller11,
  15. Matthias Boentert12,
  16. Bertold Schrank13,
  17. Johannes Prudlo14,
  18. Andrea S Winkler15,
  19. Stanislav Gorbulev16,
  20. Franceso Roselli1,
  21. Luc Dupuis17,
  22. Markus Otto1,
  23. Albert C Ludolph1,18
  1. 1 Department of Neurology, University of Ulm, Ulm, Germany
  2. 2 Institute of Epidemiology and Medical Biometry, University of Ulm, Ulm, Germany
  3. 3 Department of Neurology, Hannover Medical School, Hannover, Germany
  4. 4 Center for ALS and other motor neuron diseases, Charité - Universitätsmedizin Berlin, Berlin, Germany
  5. 5 Department of Neurology, University Hospital Bergmannsheil, Bochum, Germany
  6. 6 Department of Neurology, Technische Universität Dresden, and German Center for Neurodegenerative Diseases (DZNE), Dresden, Germany
  7. 7 Translational Neurodegeneration Section, Albrecht-Kossel, Department of Neurology, University of Rostock, Rostock, Germany
  8. 8 Department of Neurology, University Hospital Halle, Halle/Saale, Germany
  9. 9 Department of Neurology, Heidelberg University Hospital, Heidelberg, Germany
  10. 10 Department of Neurology, Jena University Hospital, Jena, Germany
  11. 11 Department of Neurology, University of Würzburg, Würzburg, Germany
  12. 12 Department of Neurology with Institute of Translational Neurology, University of Münster, Münster, Germany
  13. 13 Department of Neurology, DKD HELIOS Klinik Wiesbaden, Wiesbaden, Germany
  14. 14 Department of Neurology, Rostock University Medical Center, and German Center for Neurodegenerative Diseases (DZNE), Rostock, Germany
  15. 15 Department of Neurology, Technical University of Munich, Munich, Germany
  16. 16 Interdisciplinary Center for Clinial Trials, University Medical Center Mainz, Mainz, Germany
  17. 17 Inserm, Université de Strasbourg, Strasbourg, France
  18. 18 German Center for Neurodegenerative Diseases (DZNE), Ulm, Germany
  1. Correspondence to Dr Johannes Dorst, Neurology, University of Ulm, Ulm 89081, Germany; johannes.dorst{at}uni-ulm.de

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Introduction

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.

Methods

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 …

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Footnotes

  • 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 albert.ludolph@rku.de; 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.

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