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NCT Number: NCT06280079

Ultra-high-caloric, Fatty Diet in ALS

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).

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Key information

Conditions

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

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

RWTH Aachen, Aachen, Germany

Loading trial locations.

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

ultra-high-caloric fatty diet

Dietary Supplement

100% fat (70g), saturated fatty acids 7,5g, monounsaturated fatty acids 42,6g, polyunsaturated fatty acids 19,9g, long-chain fatty acids 100%, ratio omega-6 to omega-3 fatty acids 5:1, protein 0g, carbohydrates 0g, fiber 0g

Placebo

Other

<5% fat (<3,5g), protein 0g, carbohydrates 0g, fiber 0g

Primary outcomes

  1. Survival

    Time frame: 18 months

    Time from date of randomization until date of death, tracheostomy, or permanent continous ventilation (>22 hours per day)

Secondary outcomes

  1. Amyotrophic Lateral Sclerosis Functional Rating Scale Revised

    Time frame: 18 months

    Change per month of Amyotrophic Lateral Sclerosis Functional Rating Scale Revised

  2. Rasch Overall Amyotrophic Lateral Sclerosis Disability Scale

    Time frame: 18 months

    Change per month of Rasch Overall Amyotrophic Lateral Sclerosis Disability Scale

  3. Individual Quality of Life

    Time frame: 18 months

    Change of Euro Quality of Life 5D 5L (EQ-5D-5L) compared to baseline

  4. Slow vital capacity

    Time frame: 18 months

    Change of slow vital capacity compared to baseline

  5. Survival

    Time frame: 6 months

    Time from date of randomization until date of death, tracheostomy, or permanent continous ventilation (>22 hours per day)

  6. Survival

    Time frame: 12 months

    Time from date of randomization until date of death, tracheostomy, or permanent continous ventilation (>22 hours per day)

  7. Time to death

    Time frame: 18 months

    Time from date of randomization until date of death

  8. Time to tracheostomy

    Time frame: 18 months

    Time from date of randomization until date of tracheostomy

  9. Time to permanent continous ventilator dependence

    Time frame: 18 month

    Time from date of randomization to permanent continous ventilator dependence (>22 hours per day)

  10. Ventilation assistance-free survival

    Time frame: 18 months

    Time from date of randomization until implementation of mechanical ventilation

  11. Body Mass Index

    Time frame: 18 months

    Change of body mass index compared to baseline

  12. Council of Nutrition Appetite Questionnaire

    Time frame: 18 months

    Change of Council of Nutrition Appetite Questionnaire sum score compared to baseline

  13. Eating Habits

    Time frame: 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).

  14. Neurofilament light chain

    Time frame: 18 months

    Change of neurofilament light chain serum levels compared to baseline

  15. Amyotrophic Lateral Sclerosis Functional Rating Scale Revised Prediction Model

    Time frame: 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

  16. Neurofilament Assess Score

    Time frame: 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

Other outcomes

  1. Microtubule-associated protein 2 in serum

    Time frame: 18 months

    change of Microtubule-associated protein 2 levels in serum compared to baseline

  2. Microtubule-associated protein 2 in cerebrospinal fluid

    Time frame: 18 months

    change of microtubule-associated protein 2 levels in cerebrospinal fluid compared to baseline

  3. Ubiquitin carboxy-terminal hydrolase L1 in serum

    Time frame: 18 months

    change of ubiquitin carboxy-terminal hydrolase L1 levels in serum compared to baseline

  4. Ubiquitin carboxy-terminal hydrolase L1 in cerebrospinal fluid

    Time frame: 18 months

    change of ubiquitin carboxy-terminal hydrolase L1 levels in cerebrospinal fluid compared to baseline

  5. Transmembrane glycoprotein NMB in serum

    Time frame: 18 months

    change of transmembrane glycoprotein NMB levels in serum compared to baseline

  6. Transmembrane glycoprotein NMB in cerebrospinal fluid

    Time frame: 18 months

    change of transmembrane glycoprotein NMB levels in cerebrospinal fluid compared to baseline

  7. Human cartilage glycoprotein 39 in serum

    Time frame: 18 months

    change of human cartilage glycoprotein 39 levels in serum compared to baseline

  8. Human cartilage glycoprotein 39 in cerebrospinal fluid

    Time frame: 18 months

    change of human cartilage glycoprotein 39 levels in cerebrospinal fluid compared to baseline

  9. SNAP-25 in serum

    Time frame: 18 months

    change of SNAP-25 levels in serum compared to baseline

  10. SNAP-25 in cerebrospinal fluid

    Time frame: 18 months

    change of SNAP-25 levels in cerebrospinal fluid compared to baseline

  11. Beta-synuclein in serum

    Time frame: 18 months

    change of beta-synuclein levels in serum compared to baseline

  12. Beta-synuclein in cerebrospinal fluid

    Time frame: 18 months

    change of beta-synuclein levels in cerebrospinal fluid compared to baseline

  13. Aquaporin-4 in serum

    Time frame: 18 months

    change of aquaporin-4 levels in serum compared to baseline

  14. Aquaporin-4 in cerebrospinal fluid

    Time frame: 18 months

    change of aquaporin-4 levels in cerebrospinal fluid compared to baseline

  15. Glial fibrillary acidic protein in serum

    Time frame: 12 months

    change of glial fibrillary acidic protein levels in serum compared to baseline

  16. Glial fibrillary acidic protein in cerebrospinal fluid

    Time frame: 12 months

    change of glial fibrillary acidic protein levels in cerebrospinal fluid compared to baseline

  17. Soluble triggering receptor expressed on myeloid cell-1 in serum

    Time frame: 12 months

    change of soluble triggering receptor expressed on myeloid cell-1 levels in serum compared to baseline

  18. Soluble triggering receptor expressed on myeloid cell-1 in cerebrospinal fluid

    Time frame: 12 months

    change of soluble triggering receptor expressed on myeloid cell-1 levels in cerebrospinal fluid compared to baseline

  19. CC-chemokine ligand 2 in serum

    Time frame: 12 months

    change of CC-chemokine ligand 2 levels in serum compared to baseline

  20. CC-chemokine ligand 2 in cerebrospinal fluid

    Time frame: 12 months

    change of CC-chemokine ligand 2 levels in cerebrospinal fluid compared to baseline

  21. interleukin-1b in serum

    Time frame: 12 months

    change of interleukin-1b levels in serum compared to baseline

  22. interleukin-1b in cerebrospinal fluid

    Time frame: 12 months

    change of interleukin-1b levels in cerebrospinal fluid compared to baseline

  23. interleukin-2 in serum

    Time frame: 12 months

    change of interleukin-2 levels in serum compared to baseline

  24. interleukin-2 in cerebrospinal fluid

    Time frame: 12 months

    change of interleukin-2 levels in cerebrospinal fluid compared to baseline

  25. interleukin-4 in serum

    Time frame: 12 months

    change of interleukin-4 levels in serum compared to baseline

  26. interleukin-4 in cerebrospinal fluid

    Time frame: 12 months

    change of interleukin-4 levels in cerebrospinal fluid compared to baseline

  27. interleukin-6 in serum

    Time frame: 12 months

    change of interleukin-6 levels in serum compared to baseline

  28. interleukin-6 in cerebrospinal fluid

    Time frame: 12 months

    change of interleukin-6 levels in cerebrospinal fluid compared to baseline

  29. interleukin-10 in serum

    Time frame: 12 months

    change of interleukin-10 levels in serum compared to baseline

  30. interleukin-10 in cerebrospinal fluid

    Time frame: 12 months

    change of interleukin-10 levels in cerebrospinal fluid compared to baseline

  31. interleukin-12p70 in serum

    Time frame: 12 months

    change of interleukin-12p70 levels in serum compared to baseline

  32. interleukin-12p70 in cerebrospinal fluid

    Time frame: 12 months

    change of interleukin-12p70 levels in cerebrospinal fluid compared to baseline

  33. interleukin-17 in serum

    Time frame: 12 months

    change of interleukin-17 levels in serum compared to baseline

  34. interleukin-17 in cerebrospinal fluid

    Time frame: 12 months

    change of interleukin-17 levels in cerebrospinal fluid compared to baseline

  35. Tumor necrosis factor alpha in serum

    Time frame: 12 months

    change of tumor necrosis factor alpha levels in serum compared to baseline

  36. Tumor necrosis factor alpha in cerebrospinal fluid

    Time frame: 12 months

    change of tumor necrosis factor alpha levels in cerebrospinal fluid compared to baseline

Study contacts

Contact information is provided by the study sponsor or research team.

Johannes Dorst, Prof. Dr.

CONTACT

[email protected]

+497311775285

Sponsors and collaborators

Lead sponsor

University of Ulm

Other

Registry information

Official study title

Efficacy, Safety, and Tolerability of Ultra-high-caloric, Fatty Diet (UFD) in Amyotrophic Lateral Sclerosis (ALS)

Acronym: LIPCAL-ALS II

Important dates

Study start
2024
Primary completion
2028
Study completion
2028
First posted
Feb 28, 2024
Registry last updated
May 1, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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