Hypercaloric PEG Nutrition in ALS to Sustain Energy Homeostasis

NCT06877143 | Recruiting DMC

• 2 other identifiers: 387/23PEGASUS V 1.0
• Study Type: interventional
• Target: 76
• Locations: 1 country
• Sites: 1

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.

Conditions

Amyotrophic Lateral Sclerosis (ALS)

Keywords

ALS; PEG; hypercaloric nutrition; energy deficit

Outcome Measures

Primary Outcomes (1)

• Neurofilament light chain (NfL) in serum

  Change of neurofilament light chain (NfL) concentration in serum after 6 months compared to baseline. The change will be measured as individual NfL slope from baseline to 6 months (change per month).

  6 months

Secondary Outcomes (22)

• Survival

  6 months

• ALS functional rating scale revised (ALSFRS-R)

  6 months

• Body mass index (BMI)

  6 months

• Slow vital capacity

  6 months

• Resting energy expenditure (REE)

  6 months

Study Arms (2)

Group A: Isocaloric nutrition via PEG

OTHER

Isocaloric nutrition (100% of individual calory requirement as determined by indirect calorimetry and physical activity questionnaire) applied via PEG

Dietary Supplement: 100% of individual calory requirement

Group B: Hypercaloric nutrition via PEG

EXPERIMENTAL

Hypercaloric nutrition (120% of individual calory requirement as determined by indirect calorimetry and physical activity questionnaire) applied via PEG

Dietary Supplement: 120% of individual calory requirement

Interventions

100% of individual calory requirement DIETARY_SUPPLEMENT

Patients receive any PEG nutrition containing the calory requirement as determined by indirect calorimetry, physical activity score and the randomized group.

Group A: Isocaloric nutrition via PEG

120% of individual calory requirement DIETARY_SUPPLEMENT

Patients receive any PEG nutrition containing the calory requirement as determined by indirect calorimetry, physical activity score and the randomized group.

Group B: Hypercaloric nutrition via PEG

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Ulm: lead

Study Sites (1)

Ulm Universita, Department of Neurology

Ulm, Baden-Wurttemberg, 89081, Germany

RECRUITING

Related Links

• Desport JC, Preux PM, Truong TC, Vallat JM, Sautereau D, Couratier P. Nutritional status is a prognostic factor for survival in ALS patients. Neurology 1999; 53(5): 1059-63.
• Dupuis L, Oudart H, Rene F, Gonzalez de Aguilar JL, Loeffler JP. Evidence for defective energy homeostasis in amyotrophic lateral sclerosis: benefit of a high-energy diet in a transgenic mouse model. Proc Natl Acad Sci U S A 2004; 101(30): 11159-64.
• Dupuis L, Pradat PF, Ludolph AC, Loeffler JP. Energy metabolism in amyotrophic lateral sclerosis. Lancet Neurol 2011; 10(1): 75-82.
• Fayemendy P, Marin B, Labrunie A, et al. Hypermetabolism is a reality in amyotrophic lateral sclerosis compared to healthy subjects. J Neurol Sci 2021; 420(117257): 3.
• Dorst J, Cypionka J, Ludolph AC. High-caloric food supplements in the treatment of amyotrophic lateral sclerosis: A prospective interventional study. Amyotroph Lateral Scler Frontotemporal Degener 2013; 14(7-8): 533-6.
• Ludolph AC, Dorst J, Dreyhaupt J, et al. Effect of high-caloric nutrition on survival in amyotrophic lateral sclerosis. Ann Neurol 2019; 17(10): 25661.
• Dorst J, Schuster J, Dreyhaupt J, et al. Effect of high-caloric nutrition on serum neurofilament light chain levels in amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry 2020; 91(9): 1007-9.
• Steinacker P, Huss A, Mayer B, et al. Diagnostic and prognostic significance of neurofilament light chain NF-L, but not progranulin and S100B, in the course of amyotrophic lateral sclerosis: Data from the German MND-net. Amyotroph Lateral Scler Frontotem
• Wills AM, Hubbard J, Macklin EA, et al. Hypercaloric enteral nutrition in patients with amyotrophic lateral sclerosis: a randomised, double-blind, placebo-controlled phase 2 trial. Lancet 2014; 383(9934): 2065-72.
• Dorst J, Dupuis L, Petri S, et al. Percutaneous endoscopic gastrostomy in amyotrophic lateral sclerosis: a prospective observational study. J Neurol 2015.
• Wang S, Yuan T, Yang H, Zhou X, Cao J. Effect of complete high-caloric nutrition on the nutritional status and survival rate of amyotrophic lateral sclerosis patients after gastrostomy. American journal of translational research 2022; 14(11): 7842-51.
• Craig CL, Marshall AL, Sjöström M, et al. International physical activity questionnaire: 12-country reliability and validity. Med Sci Sports Exerc 2003; 35(8): 1381-95.

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Christine Herrmann, Dr.

  University of Ulm

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Christine Herrmann, Dr.

CONTACT

0049 731 177 5374; christine.herrmann@uni-ulm.de

Johannes Dorst, Prof. Dr.

CONTACT

0049 731 177 5285; johannes.dorst@uni-ulm.de

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dr.

Model Details: randomized controlled double-blind study

Study Record Dates

• First Submitted: February 26, 2025
• First Posted: March 14, 2025
• Study Start: March 1, 2025
• Primary Completion (Estimated): March 1, 2031
• Study Completion (Estimated): September 1, 2031
• Last Updated: May 6, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: 3 months to 5 years following article publication
• Access Criteria: Data will be shard for analyses to achieve the aims provided in the approved proposal. Proposals should be directed to christine.herrmann@uni-ulm.de; to gain access, data requestors will need to sign a data access agreement.

Locations

DE (1)