Ultra-high-caloric, Fatty Diet in ALS

Not Applicable

Recruiting

• Conditions: Amyotrophic Lateral Sclerosis

• 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.

Study Timeline

• Study First Submitted: 2024-02-19
• Study First Submitted QC: 2024-02-19
• Study First Posted: 2024-02-28
• Study Start: 2024-06-01
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-03
• Last Update Posted: 2024-12-06
• Primary Completion: 2027-06-01
• Study Completion: 2027-06-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 392

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

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)
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).
Time to tracheostomy	18 months	Time from date of randomization until date of tracheostomy

Trial Locations

Locations (23)

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

Scroll for more (13 remaining)