Ultra-high-caloric, Fatty Diet in ALS (LIPCAL-ALS II)

University of Ulm

Status: Enrolling

Conditions: Amyotrophic Lateral Sclerosis

Treatments: Other: Placebo; Dietary Supplement: Ultra-high-caloric fatty diet

Study type: Interventional

Funder types: Other

Identifiers

NCT06280079

LIPCAL-ALS II 1.1

Details and patient eligibility

About

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).

Full 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.

Enrollment: 392 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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392 participants in 2 patient groups, including a placebo group

Ultra-high-caloric fatty diet

Experimental group

Description:

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

Treatment:

Dietary Supplement: Ultra-high-caloric fatty diet

Placebo

Placebo Comparator group

Description:

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

Treatment:

Other: Placebo