Ultra-high-caloric, Fatty Diet in ALS
- Conditions
- Amyotrophic Lateral Sclerosis
- Interventions
- Other: PlaceboDietary Supplement: Ultra-high-caloric fatty diet
- Registration Number
- NCT06280079
- Lead Sponsor
- University of Ulm
- Brief Summary
This study aims at evaluating efficacy and tolerability of an ultra-high-caloric, fatty diet (UFD) compared to placebo in patients with amyotrophic lateral sclerosis (ALS).
- Detailed Description
ALS is a fatal neurodegenerative disease, leading to progressive paralysis of voluntarily innervated muscles and to death caused by respiratory failure after a mean disease duration of 2-4 years.The proposed study aims at improving survival of ALS patients by targeting metabolic parameters. ALS patients feature an intrinsic hypermetabolism as signified by an increased resting energy expenditure, which significantly contributes to progressive weight loss and cachexia. The extent of weight loss is an independent prognostic factor for survival in ALS. It has been shown that survival of ALS mice can be prolonged by applying a high-caloric nutrition. Furthermore, ALS patients feature distinct alterations of lipid metabolism, and various studies suggest a protective effect of high triglyceride serum levels.
In the precursor-study LIPCAL-ALS-I, a randomized, placebo-controlled, multicenter trial, evaluating the effects of a high-caloric fatty diet (HCFD), the primary endpoint (survival in the whole study population) was missed. However, post-hoc analysis revealed showed that HCFD (1) increased survival and reduced weight loss in normal to fast-progressing patients (patients with a functional decline measured by ALS Functional Rating Scale Revised) above the median at baseline; p=0.02), (2) slowed down functional decline (measured by Amyotrophic Lateral Sclerosis Functional Rating Scale Revised) in the whole study population (p\<0.0125), and (3) lowered neurofilament light chain (NfL) serum levels as a prognostic biomarker in the whole study population (p=0.0225).
Therefore, this study aims at prolonging survival in ALS patients by applying 1.5-fold dosage of the same intervention as in LIPCAL-ALS I in a larger number of patients, excluding patients with slow disease progression.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 392
- Possible, probable (clinically or laboratory supported) or definite amyotrophic lateral sclerosis according to the revised version of the El Escorial criteria
- Disease duration (onset of first paresis or bulbar symptoms) < 24 months
- Loss of amyotrophic lateral sclerosis functional rating scale revised of ≥ 0.33 points/month based on the formula: (48 - myotrophic lateral sclerosis functional rating scale revised score at screening visit) / (months between onset and screening visit)
- Age ≥18 years.
- Either continuously treated with a stable dose of riluzole, OR not treated with riluzole for the last 4 weeks prior to inclusion
- Either continuously treated with a stable dose of edaravone, OR not treated with edaravone for the last 4 weeks prior to inclusion
- Either continuously treated with a stable dose of sodium-phenylbutyrate/taurursodiol, OR not treated with sodium-phenylbutyrate/taurursodiol for the last 4 weeks prior to inclusion
- Capable of thoroughly understanding all information given
- full written informed consent according to good clinical practice
- Previous participation in another interventional study involving an active treatment within the preceding 4 weeks
- Tracheostomy or continuous permanent ventilator dependence (>22 hours per day)
- Pregnancy or breastfeeding
- Any medical condition known to have an association with motor neuron dysfunction which might confound or obscure the diagnosis of ALS
- Presence of any concomitant life-threatening disease or impairment likely to interfere with functional assessment.
- Evidence of a major psychiatric disorder or clinically evident dementia precluding evaluation of symptoms.
- Liable to be not cooperative or comply with study requirements as assessed by the investigator, or unable to be reached in the case of emergency
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo placebo, fluid nutritional supplement oral intake of 4 times 35 ml per day in addition to normal food intake, corresponding to +50 kcal and +3,5g fat per day Ultra-high-caloric fatty diet Ultra-high-caloric fatty diet ultra-high-caloric, high-fat, fluid nutritional supplement oral intake of 4 times 35 ml per day in addition to normal food intake, corresponding to +630 kcal and +70g fat per day
- Primary Outcome Measures
Name Time Method Survival 18 months Time from date of randomization until date of death, tracheostomy, or permanent continous ventilation (\>22 hours per day)
- Secondary Outcome Measures
Name Time Method Rasch Overall Amyotrophic Lateral Sclerosis Disability Scale 18 months Change per month of Rasch Overall Amyotrophic Lateral Sclerosis Disability Scale
Time to permanent continous ventilator dependence 18 month Time from date of randomization to permanent continous ventilator dependence (\>22 hours per day)
Time to tracheostomy 18 months Time from date of randomization until date of tracheostomy
Slow vital capacity 18 months Change of slow vital capacity compared to baseline
Time to death 18 months Time from date of randomization until date of death
Ventilation assistance-free survival 18 months Time from date of randomization until implementation of mechanical ventilation
Body Mass Index 18 months Change of body mass index compared to baseline
Neurofilament light chain 18 months Change of neurofilament light chain serum levels compared to baseline
Neurofilament Assess Score 18 months Difference between observed and predicted survival based on the Neurofilament Assess Score, a score estimating survival based on the neurofilament light chain serum baseline levels
Amyotrophic Lateral Sclerosis Functional Rating Scale Revised 18 months Change per month of Amyotrophic Lateral Sclerosis Functional Rating Scale Revised
Individual Quality of Life 18 months Change of Euro Quality of Life 5D 5L (EQ-5D-5L) compared to baseline
Survival 12 months Time from date of randomization until date of death, tracheostomy, or permanent continous ventilation (\>22 hours per day)
Amyotrophic Lateral Sclerosis Functional Rating Scale Revised Prediction Model 18 months Difference between observed and predicted decrease of Amyotrophic Lateral Sclerosis Functional Rating Scale Revised (measured as points lost per month), based on the a prediction model, which estimates disease progression based on neurofilament light chain serum baseline levels
Council of Nutrition Appetite Questionnaire 18 months Change of Council of Nutrition Appetite Questionnaire sum score compared to baseline
Eating Habits 18 months Change of Ulm Nutrition Questionnaire compared to baseline; qualitative changes on a descriptional level (the questionnaire has no sum score); the score is meant to detect changes of eating habits and has been used in the precursor study LIPCAL-ALS I (see doi: 10.1002/ana.25661).
Trial Locations
- Locations (23)
University of Ulm
🇩🇪Ulm, Germany
Diakonissenkrankenhaus Mannheim
🇩🇪Mannheim, Germany
RWTH Aachen
🇩🇪Aachen, Germany
Charité Universitätsmedizin Berlin
🇩🇪Berlin, Germany
University Clinic Bochum
🇩🇪Bochum, Germany
University Clinic Bonn
🇩🇪Bonn, Germany
Technical University Dresden
🇩🇪Dresden, Germany
University Clinic Erlangen
🇩🇪Erlangen, Germany
Alfried Krupp Krankenhaus Essen
🇩🇪Essen, Germany
University Clinic Göttingen
🇩🇪Göttingen, Germany
University Clinic Halle
🇩🇪Halle, Germany
Hannover Medical School
🇩🇪Hannover, Germany
University Clinic Jena
🇩🇪Jena, Germany
DRK Clinic Kassel
🇩🇪Kassel, Germany
Klinikum Kempten
🇩🇪Kempten, Germany
University Clinic Leipzig
🇩🇪Leipzig, Germany
University Clinic Lübeck
🇩🇪Lübeck, Germany
Technical University Munich
🇩🇪Munich, Germany
University Clinic Münster
🇩🇪Münster, Germany
University Clinic Regensburg
🇩🇪Regensburg, Germany
University Clinic Rostock
🇩🇪Rostock, Germany
DKD HELIOS Clinic Wiesbaden
🇩🇪Wiesbaden, Germany
University Clinic Würzburg
🇩🇪Würzburg, Germany