Clinical trial NCT06280079: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Amyotrophic Lateral Sclerosis
Keywords: Amyotrophic Lateral Sclerosis
High-caloric, high-fat nutrition
Survival
Randomized controlled trial
Lead sponsor: University of Ulm
Sponsor class: OTHER
First posted: 2024-02-28
Enrollment: 392
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Survival
timeFrame: 18 months
Secondary outcomes:
measure: Amyotrophic Lateral Sclerosis Functional Rating Scale Revised
timeFrame: 18 months
measure: Rasch Overall Amyotrophic Lateral Sclerosis Disability Scale
timeFrame: 18 months
measure: Individual Quality of Life
timeFrame: 18 months
measure: Slow vital capacity
timeFrame: 18 months
measure: Survival
timeFrame: 6 months
measure: Survival
timeFrame: 12 months
measure: Time to death
timeFrame: 18 months
measure: Time to tracheostomy
timeFrame: 18 months
measure: Time to permanent continous ventilator dependence
timeFrame: 18 month
measure: Ventilation assistance-free survival
timeFrame: 18 months
measure: Body Mass Index
timeFrame: 18 months
measure: Council of Nutrition Appetite Questionnaire
timeFrame: 18 months
measure: Eating Habits
timeFrame: 18 months
measure: Neurofilament light chain
timeFrame: 18 months
measure: Amyotrophic Lateral Sclerosis Functional Rating Scale Revised Prediction Model
timeFrame: 18 months
measure: Neurofilament Assess Score
timeFrame: 18 months
Other outcomes:
measure: Microtubule-associated protein 2 in serum
timeFrame: 18 months
measure: Microtubule-associated protein 2 in cerebrospinal fluid
timeFrame: 18 months
measure: Ubiquitin carboxy-terminal hydrolase L1 in serum
timeFrame: 18 months
measure: Ubiquitin carboxy-terminal hydrolase L1 in cerebrospinal fluid
timeFrame: 18 months
measure: Transmembrane glycoprotein NMB in serum
timeFrame: 18 months
measure: Transmembrane glycoprotein NMB in cerebrospinal fluid
timeFrame: 18 months
measure: Human cartilage glycoprotein 39 in serum
timeFrame: 18 months
measure: Human cartilage glycoprotein 39 in cerebrospinal fluid
timeFrame: 18 months
measure: SNAP-25 in serum
timeFrame: 18 months
measure: SNAP-25 in cerebrospinal fluid
timeFrame: 18 months
measure: Beta-synuclein in serum
timeFrame: 18 months
measure: Beta-synuclein in cerebrospinal fluid
timeFrame: 18 months
measure: Aquaporin-4 in serum
timeFrame: 18 months
measure: Aquaporin-4 in cerebrospinal fluid
timeFrame: 18 months
measure: Glial fibrillary acidic protein in serum
timeFrame: 12 months
measure: Glial fibrillary acidic protein in cerebrospinal fluid
timeFrame: 12 months
measure: Soluble triggering receptor expressed on myeloid cell-1 in serum
timeFrame: 12 months
measure: Soluble triggering receptor expressed on myeloid cell-1 in cerebrospinal fluid
timeFrame: 12 months
measure: CC-chemokine ligand 2 in serum
timeFrame: 12 months
measure: CC-chemokine ligand 2 in cerebrospinal fluid
timeFrame: 12 months
measure: interleukin-1b in serum
timeFrame: 12 months
measure: interleukin-1b in cerebrospinal fluid
timeFrame: 12 months
measure: interleukin-2 in serum
timeFrame: 12 months
measure: interleukin-2 in cerebrospinal fluid
timeFrame: 12 months
measure: interleukin-4 in serum
timeFrame: 12 months
measure: interleukin-4 in cerebrospinal fluid
timeFrame: 12 months
measure: interleukin-6 in serum
timeFrame: 12 months
measure: interleukin-6 in cerebrospinal fluid
timeFrame: 12 months
measure: interleukin-10 in serum
timeFrame: 12 months
measure: interleukin-10 in cerebrospinal fluid
timeFrame: 12 months
measure: interleukin-12p70 in serum
timeFrame: 12 months
measure: interleukin-12p70 in cerebrospinal fluid
timeFrame: 12 months
measure: interleukin-17 in serum
timeFrame: 12 months
measure: interleukin-17 in cerebrospinal fluid
timeFrame: 12 months
measure: Tumor necrosis factor alpha in serum
timeFrame: 12 months
measure: Tumor necrosis factor alpha in cerebrospinal fluid
timeFrame: 12 months
Locations:
city: Aachen
country: Germany
facility: RWTH Aachen
city: Berlin
country: Germany
facility: Charité Universitätsmedizin Berlin
city: Bochum
country: Germany
facility: University Clinic Bochum
city: Bonn
country: Germany
facility: University Clinic Bonn
city: Dresden
country: Germany
facility: Technical University Dresden
city: Erlangen
country: Germany
facility: University Clinic Erlangen
city: Essen
country: Germany
facility: Alfried Krupp Krankenhaus Essen
city: Göttingen
country: Germany
facility: University Clinic Göttingen
city: Halle
country: Germany
facility: University Clinic Halle
city: Hannover
country: Germany
facility: Hannover Medical School
city: Jena
country: Germany
facility: University Clinic Jena
city: Kassel
country: Germany
facility: DRK Clinic Kassel
city: Kempten
country: Germany
facility: Klinikum Kempten
city: Leipzig
country: Germany
facility: University Clinic Leipzig
city: Lübeck
country: Germany
facility: University Clinic Lübeck
city: Mannheim
country: Germany
facility: Diakonissenkrankenhaus Mannheim
city: Munich
country: Germany
facility: Technical University Munich
city: Münster
country: Germany
facility: University Clinic Münster
city: Regensburg
country: Germany
facility: University Clinic Regensburg
city: Rostock
country: Germany
facility: University Clinic Rostock
city: Ulm
country: Germany
facility: University of Ulm
city: Wiesbaden
country: Germany
facility: DKD HELIOS Clinic Wiesbaden
city: Würzburg
country: Germany
facility: University Clinic Würzburg
Study officials:
affiliation: University of Ulm
name: Johannes Dorst, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References: