Albert C Ludolph1,2, Johannes Dorst1, Jens Dreyhaupt3, Jochen H Weishaupt1, Jan Kassubek1, Ulrike Weiland1, Thomas Meyer4, Susanne Petri5, Andreas Hermann6,7, Alexander Emmer8, Julian Grosskreutz9, Torsten Grehl10, Daniel Zeller11, Matthias Boentert12, Bertold Schrank13, Johannes Prudlo14, Andrea S Winkler15, Stanislav Gorbulev16, Francesco Roselli1, Joachim Schuster1, Luc Dupuis17. 1. Department of Neurology, University of Ulm, Ulm, Germany. 2. German Center for Neurodegenerative Diseases, Ulm, Germany. 3. Institute of Epidemiology and Medical Biometry, University of Ulm, Ulm, Germany. 4. Charité-Universitätsmedizin Berlin, Humboldt University of Berlin, Berlin, Germany. 5. Department of Neurology, Hannover Medical School, Hannover, Germany. 6. Department of Neurology, Dresden University of Technology and German Center for Neurodegenerative Diseases, Dresden, Germany. 7. Albrecht Kossel Translational Neurodegeneration Section, Department of Neurology, University of Rostock, Rostock, Germany. 8. Department of Neurology, Halle University Hospital, Halle/Saale, Germany. 9. Department of Neurology, Jena University Hospital, Jena, Germany. 10. Department of Neurology, Bergmannsheil University Hospital, Bochum, Germany. 11. Department of Neurology, University of Würzburg, Würzburg, Germany. 12. Department of Neurology, Institute of Translational Neurology, Münster University Hospital, Münster, Germany. 13. Department of Neurology, Deutsche Klinik für Diagnostik HELIOS Clinic of Wiesbaden, Wiesbaden, Germany. 14. Department of Neurology, University of Rostock, Rostock, Germany. 15. Department of Neurology, Technical University of Munich, Munich, Germany. 16. Interdisciplinary Center for Clinical Trials, Mainz University Medical Center, Mainz, Germany. 17. National Institute of Health and Medical Research, University of Strasbourg, Strasbourg, France.
Abstract
OBJECTIVE: Weight loss has been identified as a negative prognostic factor in amyotrophic lateral sclerosis, but there is no evidence regarding whether a high-caloric diet increases survival. Therefore, we sought to evaluate the efficacy of a high-caloric fatty diet (HCFD) for increasing survival. METHODS: A 1:1 randomized, placebo-controlled, parallel-group, double-blinded trial (LIPCAL-ALS study) was conducted between February 2015 and September 2018. Patients were followed up at 3, 6, 9, 12, 15, and 18 months after randomization. The study was performed at 12 sites of the clinical and scientific network of German motor neuron disease centers (ALS/MND-NET). Eligible patients were randomly assigned (1:1) to receive either HCFD (405kcal/day, 100% fat) or placebo in addition to riluzole (100mg/day). The primary endpoint was survival time, defined as time to death or time to study cutoff date. RESULTS:Two hundred one patients (80 female, 121 male, age = 62.4 ± 10.8 years) were included. The confirmatory analysis of the primary outcome survival showed a survival probability of 0.39 (95% confidence interval [CI] = 0.27-0.51) in the placebo group and 0.37 (95% CI = 0.25-0.49) in the HCFD group, both after 28 months (point in time of the last event). The hazard ratio was 0.97, 1-sided 97.5% CI = -∞ to 1.44, p = 0.44. INTERPRETATION: The results provide no evidence for a life-prolonging effect of HCFD for the whole amyotrophic lateral sclerosis population. However, post hoc analysis revealed a significant survival benefit for the subgroup of fast-progressing patients. ANN NEUROL 2020;87:206-216.
RCT Entities:
OBJECTIVE:Weight loss has been identified as a negative prognostic factor in amyotrophic lateral sclerosis, but there is no evidence regarding whether a high-caloric diet increases survival. Therefore, we sought to evaluate the efficacy of a high-caloric fatty diet (HCFD) for increasing survival. METHODS: A 1:1 randomized, placebo-controlled, parallel-group, double-blinded trial (LIPCAL-ALS study) was conducted between February 2015 and September 2018. Patients were followed up at 3, 6, 9, 12, 15, and 18 months after randomization. The study was performed at 12 sites of the clinical and scientific network of German motor neuron disease centers (ALS/MND-NET). Eligible patients were randomly assigned (1:1) to receive either HCFD (405kcal/day, 100% fat) or placebo in addition to riluzole (100mg/day). The primary endpoint was survival time, defined as time to death or time to study cutoff date. RESULTS: Two hundred one patients (80 female, 121 male, age = 62.4 ± 10.8 years) were included. The confirmatory analysis of the primary outcome survival showed a survival probability of 0.39 (95% confidence interval [CI] = 0.27-0.51) in the placebo group and 0.37 (95% CI = 0.25-0.49) in the HCFD group, both after 28 months (point in time of the last event). The hazard ratio was 0.97, 1-sided 97.5% CI = -∞ to 1.44, p = 0.44. INTERPRETATION: The results provide no evidence for a life-prolonging effect of HCFD for the whole amyotrophic lateral sclerosis population. However, post hoc analysis revealed a significant survival benefit for the subgroup of fast-progressing patients. ANN NEUROL 2020;87:206-216.
Authors: Colin J Mahoney; Rebekah M Ahmed; William Huynh; Sicong Tu; Jonathan D Rohrer; Richard S Bedlack; Orla Hardiman; Matthew C Kiernan Journal: CNS Drugs Date: 2021-05-15 Impact factor: 5.749
Authors: Ikjae Lee; Mohamed Kazamel; Tarrant McPherson; Jeremy McAdam; Marcas Bamman; Amy Amara; Daniel L Smith; Peter H King Journal: PLoS One Date: 2021-05-06 Impact factor: 3.240