Clinical trial NCT06877143: Hypercaloric PEG Nutrition in ALS to Sustain Energy Homeostasis
Official title: Hypercaloric PEG Nutrition in ALS to Sustain Energy Homeostasis
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Amyotrophic Lateral Sclerosis (ALS)
Keywords: ALS
PEG
hypercaloric nutrition
energy deficit
Lead sponsor: University of Ulm
Sponsor class: OTHER
First posted: 2025-03-14
Enrollment: 76
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: randomized controlled double-blind study
Primary purpose: TREATMENT

Brief summary: Weight loss is a known negative prognostic factor in amyotrophic lateral sclerosis (ALS). Over the last years, various interventional studies targeting the energy deficit in ALS yielded promising results; however,it is still unclear which kind of nutrition or nutritional supplement is most beneficial. Moreover, there is lack of evidence regarding interventions in patients with a PEG in later disease stages.In a pilot study conducted in 2013, it was demonstrated that body weight can be stabilized in ALS by applying either a fat-rich or carbohydrate-rich high-caloric food supplement. In 2014, Wills et al. conducted a placebo-controlled randomized controlled pilot study, which indicated that a carbohydrate-rich, hypercaloric diet, consisting in 125% of estimated energy requirements as determined by indirect calorimetry, in patients fed via percutaneous endoscopic gastrostomy was safe and well tolerated. Moreover, these patients showed longer survival than patients fed with a fat-rich, hypercaloric diet or an isocaloric diet . Hypercaloric, high-carbohydrate diet also showed beneficial effects on body weight and Body Mass Index . Although these results were promising, the low number of patients (n=24) was a severe limiting factor of this study. The aim of this study is to investigate the effect of a hypercaloric PEG nutrition, consisting of 120% of estimated calorie requierements, compared to an isocaloric nutrition. Individual energy requirement is determined by performing indirect calorimetry and activity questionnaire. The investigators hypothsize, that a hypercaloric PEG nutrition slows down disease progression as measured by neurofilament light chains (NfL) in serum after 6 months compared to placebo. Power calculation relies on the results of the lipids and calories for ALS (LIPCAL-ALS) study which tested the effect of an oral high-caloric fatty nutritional supplement in ALS. The study revealed that NfL serum values declined significantly in the intervention group while remaining stable in the placebo group over the course of the study. Assuming a similar effect size, we calculated that 76 patients had to be included in the current trial.

Detailed description: Patients eligible for study participation will be randomized to one of two groups (hypercaloric or isocaloric diet) at baseline visit. Intervention or control diet will be administered as an add-on to standard therapy. Calory requirement will be individually determined by indirect calorimetry which measures resting energy expenditure (REE) and by collecting physical activity data. Indirect calorimetry is a non-invasive procedure which allows to calculate resting energy expenditure by measuring carbon dioxide and oxygen in the expired air using a canopy hood or a full-face mask. For both groups, a standard PEG nutrition featuring a balanced ratio of fat, carbohydrates, and protein according to human requirements will be used (e.g. Fresenius Fresubin® Energy Fibre/2250 Complete).

PEG nutrition used in this study (e.g. Fresenius Fresubin® Energy Fibre/2250 Complete) is routinely used in clinical practice for feeding of patients with ALS and PEG. It is known to be well tolerable and safe. In few cases of intolerance, this standard tube feeding may be switched to another product (e. g. HiPP Sondennahrung), but the amount of calories will not be changed.

In clinical routine, energy needs are usually estimated using the Harris-Benedict-formula, based on body weight, height, sex and age. However, this formula only provides approximate values. Therefore, in this study, indirect calorimetry is used to obtain precise values of energy needs. The German version of the International Physical Activity Questionnaire Short Last 7 Days Self-administered Format (IPAQ) is used for determining the physical activity level. The total energy requirement is calculated by adding the resting energy expenditure and the activity-related calorie requirement.

In the control group, 100% of the estimated calorie requirement is administered with the goal of covering energy needs and stabilizing body weight. The hypercaloric diet in the intervention group consists in 120% of the calorie requirement determined by indirect calorimetry. Resting energy expenditure in ALS patients is 14% higher than in a healthy control cohort. We assume that activity-related energy expenditure is increased similarly. Therefore, the hypercaloric diet consisting in 120% of calorie requirement aims to cover these additional energy needs. Similarly, a recent study in patients with PEG used 125% of calorie requirement.

Eligibility criteria: Inclusion Criteria:

* Possible, probable (clinically or laboratory) or definite ALS according to the revised version of the El Escorial World Federation of Neurology criteria 1
* Loss of ALS functional rating scale revised (ALSFRS-R) of ≥ 0.33 points per month since onset (first paresis) based on the formula: (48 - Score at Screening Visit) / (Months between Onset and Screening Visit)
* Nutrition via PEG
* Age ≥18 years
* Intake of a stable dose of riluzole for at least 4 weeks, or no riluzole
* Capable of thoroughly understanding all information given and giving full informed consent according to GCP

Exclusion Criteria:

* Previous participation in another interventional study within the preceding 4 weeks
* Absence of adequate social support and cooperation, or personal motivation (in the judgment of the investigator) to complete the study satisfactorily
* Pregnancy or breast-feeding females
* Evidence of a major psychiatric disorder or clinically evident dementia

Primary outcomes:
measure: Neurofilament light chain (NfL) in serum
timeFrame: 6 months
Secondary outcomes:
measure: Survival
timeFrame: 6 months
measure: ALS functional rating scale revised (ALSFRS-R)
timeFrame: 6 months
measure: Body mass index (BMI)
timeFrame: 6 months
measure: Slow vital capacity
timeFrame: 6 months
measure: Resting energy expenditure (REE)
timeFrame: 6 months
measure: Individual Quality of Life
timeFrame: 6 months
measure: Appetite
timeFrame: 6 months
measure: Eating habits
timeFrame: 6 months
measure: Adverse Events
timeFrame: 6 months
measure: Fatt mass
timeFrame: 6 months
measure: Total Body Water
timeFrame: 6 months
measure: Muscle Mass
timeFrame: 6 months
measure: Fat Free Mass
timeFrame: 6 months
measure: Body Cell Mass
timeFrame: 6 months
measure: Extracellular Mass
timeFrame: 6 months
measure: Lean Body Mass
timeFrame: 6 months
measure: Beta Hydroxybutyrate
timeFrame: 6 months
measure: Acetoacetate
timeFrame: 6 months
measure: Acetone
timeFrame: 6 months
measure: Lipid metabolism
timeFrame: 6 months
measure: Lipid metabolism
timeFrame: 6 months
measure: Lipid metabolism
timeFrame: 6 months
Other outcomes:
Locations:
city: Ulm
country: Germany
facility: Ulm Universita, Department of Neurology
state: Baden-Württemberg
Study officials:
affiliation: University of Ulm
name: Christine Herrmann, Dr.
role: PRINCIPAL_INVESTIGATOR
References: