Safety and Tolerability Ultra-high-caloric Food Supplements in Amyotrophic Lateral Sclerosis (ALS) (TOLCAL)

Safety and Tolerability of Fat-rich vs. Carbohydrate-rich High-caloric Food Supplements in Patients With Amyotrophic Lateral Sclerosis (ALS)

The LIPCAL-ALS study (NCT02306590) has provided preliminary evidence that a high-caloric nutrition might prolong survival in fast-progressing ALS patients. Since increasing the amount of calories of the intervention might possibly increase the beneficial effect, the investigators seek to investigate whether an ultra-high caloric diet (UHCD), featuring the double amount of calories compared to LIPCAL-ALS, will be well tolerated by ALS patients and may serve as an intervention for a potential LIPCALII study. For this purpose, the investigators will compare two different UHCDs (one fat-rich and one carbohydrate-rich) with regard to safety and tolerability over a time frame of 4 weeks. A third group will receive the original diet from LIPCAL, and a fourth group will receive no intervention (control group).

Study Overview

• Status: Completed
• Conditions: Amyotrophic Lateral Sclerosis
• Intervention / Treatment: Dietary supplement: high-caloric fatty diet; Dietary supplement: ultra-high-caloric fatty diet; Dietary supplement: ultra-high-caloric carbohydrate-rich diet

• Study Type: Interventional
• Enrollment (Actual): 64
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Baden-Wurttemberg
    • Ulm, Baden-Wurttemberg, Germany, 89081
      • University of Ulm, Department of Neurology

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:

• Diagnosis of Amyotrophic Lateral Sclerosis (ALS) according to the revised version of the El Escorial criteria (Ludolph et al. 2015)
• Slope of ALS Functional Rating Scale Revised (ALSFRS-R) of >0.25 points per month at baseline visit based on the formula (48 - score at baseline visit) / (time between date of first symptom and baseline visit)
• stable on standard therapy riluzole (100 mg/day) for at least 4 weeks
• capable of thoroughly understanding all information given and giving full informed consent according to good clinical practice (GCP)

Exclusion Criteria:

• already taking any dietary supplements
• participation in another clinical trial within the preceding 8 weeks
• tracheostomy or assisted ventilation of any type which exceeds 23 hours per day
• pregnancy or breast-feeding females

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: high-caloric fatty diet; intake of 405 kcal (45g fat) per day in addition to normal food intake	Dietary supplement: high-caloric fatty diet; see arm/group description
EXPERIMENTAL: ultra-high-caloric fatty diet; intake of 810 kcal (90g fat) per day in addition to normal food intake	Dietary supplement: ultra-high-caloric fatty diet; see arm/group description
EXPERIMENTAL: ultra-high-caloric carbohydrate-rich diet; intake of 900 kcal (111.4g carbohydrate, 34.9g fat, 36.0g protein) in addition to normal food intake	Dietary supplement: ultra-high-caloric carbohydrate-rich diet; see arm/group description
NO_INTERVENTION: control; normal food intake (no intervention)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events and Serious Adverse Events	Incidence of Adverse Events and Serious Adverse Events	4 weeks
Laboratory values	Incidence of abnormalities in clinical laboratory assessments, vital signs and physical examinations	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Appetite	Change of Appetite-Score (Council of Nutrition appetite questionnaire, CNAQ) compared to baseline; values 8-40; higher values mean better appetite	2 weeks; 4 weeks
Eating Habits	Change in eating habits as evaluated by a standardized questionnaire (Ulmer eating habits questionnaire); descriptive information and evaluation; no overall score	2 weeks; 4 weeks
Taste of Intervention	taste of intervention (visual analogous scale); values 1-9, higher values mean better taste	2 weeks; 4 weeks
Body Weight	change of body weight compared to baseline	2 weeks; 4 weeks
Biomarkers	change of neurofilament light chains (NfL) in serum	4 weeks
Adverse Events and Serious Adverse Events	Incidence of Adverse Events and Serious Adverse Events (evaluation via phone call 2 weeks after intervention was finished)	6 weeks
ALSFRS-R	change of Amyotrophic Lateral Sclerosis Functional Rating Scale Revised (ALSFRS-R) compared to baseline; values 0-48; higher values mean less impairment	4 weeks

Collaborators and Investigators

• Sponsor: Albert Christian Ludolph, Prof.
• Collaborators: Nutritia GmbH, 91052 Erlangen, Germany
• Investigators: Principal Investigator: Johannes Dorst, PD Dr., University of Ulm

Publications and helpful links

General Publications

• Ludolph A, Drory V, Hardiman O, Nakano I, Ravits J, Robberecht W, Shefner J; WFN Research Group On ALS/MND. A revision of the El Escorial criteria - 2015. Amyotroph Lateral Scler Frontotemporal Degener. 2015;16(5-6):291-2. doi: 10.3109/21678421.2015.1049183. Epub 2015 Jun 29. No abstract available.

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 26, 2019
• Primary Completion (ACTUAL): April 5, 2021
• Study Completion (ACTUAL): April 5, 2021

Study Registration Dates

• First Submitted: November 19, 2019
• First Submitted That Met QC Criteria: November 19, 2019
• First Posted (ACTUAL): November 21, 2019

Study Record Updates

• Last Update Posted (ACTUAL): April 29, 2021
• Last Update Submitted That Met QC Criteria: April 28, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• 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: TOLCAL

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data will be available beginning 3 months and ending 5 years following article publication. Data will be shard with researchers who provide a methodologically sound proposal. Data will be shared for analyses to achieve the aims in the approved proposal. Proposals should be directed to johannes.dorst@uni-ulm.de; to gain access, data requestors will need to sign a data acess agreement. The study protocol will be available for 5 years at htpps://www.uniklinik-ulm.de/neurologie.html.
• IPD Sharing Time Frame: 3 month after publication until 5 years after publication
• IPD Sharing Access Criteria: Data will be shared with researchers who provide a methodologically sound proposal. Data will be shared for analyses to achieve the aims in the approved proposal. Proposals should be directed to johannes.dorst@uni-ulm.de; to gain access, data requestors will need to sign a data acess agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No