Efficacy, Safety and Tolerability of High Lipid and Calorie Supplementation in Amyotrophic Lateral Sclerosis

The primary objective of the trial is to investigate the survival time (the time from randomization until death or date of end of the study) compared between control group and experimental group.

This is a prospective, multicenter, randomized, stratified, parallel-group, double-blind trial comparing placebo with high caloric fatty diet for drinking as add-on therapy to 100 mg riluzole in amyotrophic lateral sclerosis (ALS) in 200 enrolled patients. For entry, the El Escorial Criteria for the diagnosis of ALS will be used. The patients have to be stable on riluzole at least 4 weeks prior to randomization.

Study Overview

• Status: Completed
• Conditions: Amyotrophic Lateral Sclerosis
• Intervention / Treatment: Dietary supplement: Placebo; Dietary supplement: Calogen

• Study Type: Interventional
• Enrollment (Actual): 207
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 13353
    • Department of Neurology, Humboldt University
  • Bochum, Germany, 44789
    • Neurologische Universitätsklinik Bergmannsheil
  • Münster, Germany, 48149
    • Department für Neurologie - Klinik für Schlafmedizin und Neuromuskuläre Erkrankungen Universitätsklinikum Münster
  • Wiesbaden, Germany, 65191
    • Department of Neurology, DKD HELIOS Klinik
  • Baden-Württemberg
    • Ulm, Baden-Württemberg, Germany, 89081
      • Department of Neurology, University of Ulm
  • Bayern
    • Wuerzburg, Bayern, Germany, 91054
      • Department of Neurology, University of Wuerzburg
  • Mecklenburg-Vorpommern
    • Rostock, Mecklenburg-Vorpommern, Germany, D-18147
      • Department of Neurology, University of Rostock
  • Niedersachsen
    • Hannover, Niedersachsen, Germany, 30625
      • Department of Neurology, Medical School Hannover
  • Sachsen
    • Dresden, Sachsen, Germany, D-01307
      • Department of Neurology, TU Dresden
  • Sachsen-Anhalt
    • Halle/Saale, Sachsen-Anhalt, Germany, 06097
      • Department of Neurology, University of Halle-Wittenberg
  • Thueringen
    • Jena, Thueringen, Germany, D-07747
      • Department of Neurology, University of Jena

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Possible, probable (clinically or laboratory supported) or definite ALS according to the revised version of the El Escorial criteria (Brooks et al. 2000)
• Disease duration < 36 months
• Vital capacity of more than 50% of normal (defined as slow vital capacity, best of three measurements)
• Age ≥18 years
• Continuously treated with 100 mg riluzole daily for at least four weeks
• Capable of thoroughly understanding all information given and giving full informed consent according to GCP
• Willing to complete a diet questionnaire throughout participation in the study

Exclusion Criteria:

• Simultaneous participation in another interventional clinical study
• Previous participation in a drug clinical trial where last intake of the trial drug was within the last 12 weeks
• Known sensitivity or intolerance to rape oil or sunflower oil, or components thereof
• Tracheostomy
• Patients with gastrostomy
• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Study Intervention; High caloric fatty diet for drinking (100% lipids, 4.5 kcal/ml) 405 kcal/90 ml/day in addition to daily food intake and standard of care; corresponding to an additional intake of 45 g fat per day	Dietary supplement: Calogen
Placebo Comparator: Placebo; Placebo drinking solution 8 kcal/90ml/day in addition to daily food intake and standard of care	Dietary supplement: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Survival in ALS-patients with study intervention compared to placebo	18 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Change of total ALS functional rating scale revised (ALSFRS-R)	18 months
Change of individual quality of life (SEIQoL)	18 months
Change of the slow vital capacity (sVC)	18 months
Time to tracheostomy or death (combined)	18 months
Change of Body Mass Index (BMI)	18 months
Change of Appetite-Score, Council of Nutrition appetite questionnaire (CNAQ)	18 months

Collaborators and Investigators

• Sponsor: University of Ulm
• Investigators: Principal Investigator: Albert C. Ludolph, MD, Prof., University Ulm

Publications and helpful links

General Publications

• Witzel S, Frauhammer F, Steinacker P, Devos D, Pradat PF, Meininger V, Halbgebauer S, Oeckl P, Schuster J, Anders S, Dorst J, Otto M, Ludolph AC. Neurofilament light and heterogeneity of disease progression in amyotrophic lateral sclerosis: development and validation of a prediction model to improve interventional trials. Transl Neurodegener. 2021 Aug 26;10(1):31. doi: 10.1186/s40035-021-00257-y.

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2015
• Primary Completion (Actual): January 1, 2018
• Study Completion (Actual): September 1, 2018

Study Registration Dates

• First Submitted: December 1, 2014
• First Submitted That Met QC Criteria: December 2, 2014
• First Posted (Estimate): December 3, 2014

Study Record Updates

• Last Update Posted (Actual): February 26, 2019
• Last Update Submitted That Met QC Criteria: February 25, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Keywords: quality of life; survival; amyotrophic lateral sclerosis; survival time; ALS Functional Rating Scale
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuromuscular Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Sclerosis; Motor Neuron Disease; Amyotrophic Lateral Sclerosis
• Other Study ID Numbers: LIPCAL-ALS