- LIPCAL-ALS II
Clinical Studies
Current Studies
- PEGASUS – Ketogenic PEG nutrition in ALS to sustain energy homeostasis
Previous studies have shown beneficial effects of a high-caloric diet on disease progression. In addition, mice fed with a ketogenic diet showed slower decline in motor function and higher body weight in an ALS mouse model (Zhao et al. 2006).A ketogenic diet consists of a fat-rich, carbohydrate-low diet that causes a metabolic switch inducing production of ketone bodies in the liver. To date, a ketogenic diet has not been tested in ALS patients. This will be the first study to administer a ketogenic diet to human ALS patients. A hypercaloric standard diet will also be tested. The study will be conducted over 6 months with 3 on-site visits and 2 phone visits. At the beginning of the study, caloric requirements will be determined individually for each patient using indirect calorimetry and an activity questionnaire. Patients will then be randomized to one of three study groups (38 patients each):
Ketogenic group: Patients receive an isocaloric ketogenic diet covering 100% of caloric requirements
Hypercaloric group: Patients receive a standard hypercaloric diet providing 120% of individual caloric needs.
Control group: Patients receive a standard isocaloric diet that meets 100% of caloric requirements.
The primary endpoint will be serum neurofilament light chain (NfL) levels after 6 months.
The study is a multicenter study. If you are interested in participating, please contact Dr. Christine Herrmann (Department of Neurology, Ulm University):
- Multicentric Longitudinal Study on Non-Motor Symptoms in Patients with Amyotrophic Lateral Sclerosis (ALS)
Few clinical studies have investigated non-motor symptoms in ALS patients, and only about 1% of publications address these symptoms. The existing studies use various outcome measures, leading to a wide range of reported frequencies of non-motor symptoms. Despite the substantial impact of non-motor symptoms on patients’ quality of life, they are often underdiagnosed and/or unreported. This study aims to systematically analyze the frequency and severity of non-motor symptoms in ALS through a multicenter, longitudinal approach.Objectives of the StudyCharacterization of non-motor symptoms in ALS
– Description of the “natural history” of non-motor symptoms in ALS
– Correlation between non-motor symptoms in ALS with:
– Disease progression
– Phenotype/Genotype
– Markers of neurodegeneration (neurofilaments)
– Depression and quality of life
Patient interviews will be conducted online using a professional survey platform (SoSciSurvey) (https://www.soscisurvey.de/). Each included patient will receive an invitation to participate in the interview via an individualized link and password, ensuring the anonymity of the participants. The online format not only facilitates convenience but also allows for secure data collection and storage. The interviews will be conducted at three time points: baseline, after six months, and after one year.
Interested centers are invited to contact Dr. Bogdan Bjelica (MHH Hannover) via email:
Completed Studies
In recent years, several multicenter, randomized, placebo-controlled, DFG- and BMBF-funded clinical trials have been conducted at the initiative of centers of the German ALS/MND Network:
- LIPCAL-ALS (high-calorie high-fat dietary supplementation vs. placebo): 12 sites, enrollment of 207 patients in 14 months; NCT02306590. The study found evidence of a beneficial effect of high-calorie, high-fat supplementation on survival, motor function, body weight, and neurofilaments, especially in rapidly progressive cases.
Ludolph AC, Dorst J, Dreyhaupt J, et al. Effect of high-caloric nutrition on survival in amyotrophic lateral sclerosis. Annals of neurology 2019; 17(10): 25661.
Dorst J, Schuster J, Dreyhaupt J, et al. Effect of high-caloric nutrition on serum neurofilament light chain levels in amyotrophic lateral sclerosis. Journal of neurology, neurosurgery, and psychiatry 2020; 91(9): 1007-9.
- RAS-ALS (rasagiline vs placebo) : 15 sites, enrollment of 252 patients in 15 months; NCT01879241. Post-hoc analyses of the study found evidence of prolonged survival and slowed loss of motor function in rapidly progressive patients on rasagiline.
Ludolph AC, Schuster J, Dorst J, et al. Safety and efficacy of rasagiline as an add-on therapy to riluzole in patients with amyotrophic lateral sclerosis: a randomised, double-blind, parallel-group, placebo-controlled, phase 2 trial. Lancet neurology 2018; 18(18): 30176-5.
- GERP-ALS (pioglitazone vs placebo): 15 sites, enrolling 211 patients over 9 months; NCT00690118. This study found no evidence of efficacy of pioglitazone in ALS. There was evidence of altered metabolism and hypothalamic affection in ALS patients.
Dupuis L, Dengler R, Heneka MT, et al. A randomized, double blind, placebo-controlled trial of pioglitazone in combination with riluzole in amyotrophic lateral sclerosis. PloS one 2012; 7(6): e37885
- ROCK-ALS (fasudil vs placebo): 15 sites, enrollment of 120 patients; NCT03792490. Enrollment for this study is complete and results are eagerly awaited.
Lingor P, Weber M, Camu W, et al. ROCK-ALS: Protocol for a Randomized, Placebo-Controlled, Double-Blind Phase IIa Trial of Safety, Tolerability and Efficacy of the Rho Kinase (ROCK) Inhibitor Fasudil in Amyotrophic Lateral Sclerosis.Front Neurol. 2019 Mar 27;10:293. doi: 10.3389/fneur.2019.00293.
Collaborative projects with internal and external partners
- JPND project NEEDSinALS with cooperation partners in Sweden and Poland
http://www.NEEDSinALS.com - Establishment of ECAS in Germany together with MND-NET partners
http://www.ECAS.network - Participation in the International Human Toponom (HUTO) project
https://www.toposnomos.com/ - Prognostic factors in ALS: A comparison between Germany and China
https://pubmed.ncbi.nlm.nih.gov/30923935/ - SOD1 mutations in ALS: A comparison between the Chinese and the German population
https://pubmed.ncbi.nlm.nih.gov/34711284/ - International collaborative project “The role of MSH3 and PMS2 in modifying C9orf72 related ALS”
- premodiALS study: Multinational study on the presymptomatic signature of ALS
https://www.premodials.med.tum.de - ROCK-ALS: A phase II clinical trial evaluating the safety, tolerability, and efficacy of the Rho-kinase inhibitor fasudil as a novel disease-modifying therapy in amyotrophic lateral sclerosis (ALS) with partners from France and Switzerland.
NCT03792490 - NISALS – Neuroimaging Society in Amyotrophic Lateral Sclerosis. NISALS has existed since 2010 and has a pool of MRI images of ALS patients
https://nisals.com/
- CALSNIC – Multidisciplinary team of neurologists, MR scientists, biostatisticians, etc., distributed among several academic centers
https://calsnic.org/ - Cooperation with DZNE: A cooperation agreement between MND-NET and DZNE regulates and enables joint projects
- Boris Canessa ALS Foundation: NF-L study in ALS.
https://canessa-als-stiftung.org - Ambulanzpartner care network ID-ALS study
ambulanzpartner.de - DFG funded sequencing project, aiming to find new ALS genes: “Uncovering novel causes and modifiers of ALS by nuclear and mitochondrial genome sequencing”
- Cooperation project of the TU Dresden: Deficits and potential for improvement in the psychosocial and palliative care of ALS patients in Germany
- Preclinical gene carrier study for ALS and FTD
- Hardship program Tofersen – Treatment of 25 patients of the MND-NET at 11 centers
- Expert Committee Electrophysiology: Establishment of an electrophysiological standard in the context of ALS diagnosis
- Consensus of the ALSFRS-R: MND-NET centers standardize the German version of the ALS Function Scale
- Autopsy study (Prof. J. Weis, Aachen)
- Swabian ALS-Register
- ALS-Register Rhineland-Palatinate
Please contact the respective expert committee if you are interested.
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