Ultra-high-caloric, Fatty Diet in ALS

Official title

Efficacy, Safety, and Tolerability of Ultra-high-caloric, Fatty Diet (UFD) in Amyotrophic Lateral Sclerosis (ALS)

Overview

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.

Interventions

• Dietary supplement Ultra-high-caloric fatty diet
  100% fat (70g), saturated fatty acids 7,5g, monounsaturated fatty acids 42,6g, polyunsaturated fatty acids 19,9g, long-chain fatty acids 100%, ratio omega-6 to omega-3 fatty acids 5:1, protein 0g, carbohydrates 0g, fiber 0g
• Other Placebo
  \<5% fat (\<3,5g), protein 0g, carbohydrates 0g, fiber 0g

Primary outcome measures

• Survival [Time frame: 18 months]

Secondary outcome measures (12)

• Amyotrophic Lateral Sclerosis Functional Rating Scale Revised [Time frame: 18 months]
• Rasch Overall Amyotrophic Lateral Sclerosis Disability Scale [Time frame: 18 months]
• Individual Quality of Life [Time frame: 18 months]
• Slow vital capacity [Time frame: 18 months]
• Survival [Time frame: 6 months]
• Survival [Time frame: 12 months]
• Time to death [Time frame: 18 months]
• Time to tracheostomy [Time frame: 18 months]
• Time to permanent continous ventilator dependence [Time frame: 18 month]
• Ventilation assistance-free survival [Time frame: 18 months]
• Body Mass Index [Time frame: 18 months]
• Council of Nutrition Appetite Questionnaire [Time frame: 18 months]

Eligibility criteria

Inclusion criteria

• 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

Exclusion criteria

• 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

Germany · 23 centers

• RWTH Aachen — Aachen
• Charité Universitätsmedizin Berlin — Berlin
• University Clinic Bochum — Bochum
• University Clinic Bonn — Bonn
• Technical University Dresden — Dresden
• University Clinic Erlangen — Erlangen
• Alfried Krupp Krankenhaus Essen — Essen
• University Clinic Göttingen — Göttingen
• … and 15 more centers

Identifiers

NCT: NCT06280079 · LIPCAL-ALS II 1.1

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗