Ultra-high-caloric, Fatty Diet in ALS

NCT ID: NCT06280079

Last Updated: 2024-12-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

392 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-06-01

Study Completion Date

2027-06-01

Brief Summary

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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).

Detailed Description

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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.

Conditions

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Amyotrophic Lateral Sclerosis

Keywords

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Amyotrophic Lateral Sclerosis High-caloric, high-fat nutrition Survival Randomized controlled trial

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Ultra-high-caloric fatty diet

ultra-high-caloric, high-fat, fluid nutritional supplement oral intake of 4 times 35 ml per day in addition to normal food intake, corresponding to +630 kcal and +70g fat per day

Group Type EXPERIMENTAL

Ultra-high-caloric fatty diet

Intervention Type 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

placebo, fluid nutritional supplement oral intake of 4 times 35 ml per day in addition to normal food intake, corresponding to +50 kcal and +3,5g fat per day

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type OTHER

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

Interventions

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Ultra-high-caloric fatty diet

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

Intervention Type DIETARY_SUPPLEMENT

Placebo

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

Intervention Type OTHER

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Ulm

OTHER

Sponsor Role lead

Responsible Party

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Albert Christian Ludolph, Prof.

Prof. Dr.

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Johannes Dorst, Prof. Dr.

Role: PRINCIPAL_INVESTIGATOR

University of Ulm

Locations

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RWTH Aachen

Aachen, , Germany

Site Status NOT_YET_RECRUITING

Charité Universitätsmedizin Berlin

Berlin, , Germany

Site Status RECRUITING

University Clinic Bochum

Bochum, , Germany

Site Status NOT_YET_RECRUITING

University Clinic Bonn

Bonn, , Germany

Site Status NOT_YET_RECRUITING

Technical University Dresden

Dresden, , Germany

Site Status NOT_YET_RECRUITING

University Clinic Erlangen

Erlangen, , Germany

Site Status NOT_YET_RECRUITING

Alfried Krupp Krankenhaus Essen

Essen, , Germany

Site Status NOT_YET_RECRUITING

University Clinic Göttingen

Göttingen, , Germany

Site Status NOT_YET_RECRUITING

University Clinic Halle

Halle, , Germany

Site Status NOT_YET_RECRUITING

Hannover Medical School

Hanover, , Germany

Site Status NOT_YET_RECRUITING

University Clinic Jena

Jena, , Germany

Site Status NOT_YET_RECRUITING

DRK Clinic Kassel

Kassel, , Germany

Site Status NOT_YET_RECRUITING

Klinikum Kempten

Kempten, , Germany

Site Status NOT_YET_RECRUITING

University Clinic Leipzig

Leipzig, , Germany

Site Status NOT_YET_RECRUITING

University Clinic Lübeck

Lübeck, , Germany

Site Status RECRUITING

Diakonissenkrankenhaus Mannheim

Mannheim, , Germany

Site Status RECRUITING

Technical University Munich

Munich, , Germany

Site Status NOT_YET_RECRUITING

University Clinic Münster

Münster, , Germany

Site Status NOT_YET_RECRUITING

University Clinic Regensburg

Regensburg, , Germany

Site Status NOT_YET_RECRUITING

University Clinic Rostock

Rostock, , Germany

Site Status NOT_YET_RECRUITING

University of Ulm

Ulm, , Germany

Site Status RECRUITING

DKD HELIOS Clinic Wiesbaden

Wiesbaden, , Germany

Site Status RECRUITING

University Clinic Würzburg

Würzburg, , Germany

Site Status NOT_YET_RECRUITING

Countries

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Germany

Central Contacts

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Johannes Dorst, Prof. Dr.

Role: CONTACT

Phone: +497311775285

Email: [email protected]

Facility Contacts

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Robert Brunkhorst, Dr.

Role: primary

André Maier, Dr.

Role: primary

Ute Weyen, Dr.

Role: primary

Patrick Weydt, Dr.

Role: primary

René Günther, Dr.

Role: primary

Jürgen Winkler, Prof. Dr.

Role: primary

Torsten Grehl, Dr.

Role: primary

Jan C Koch, Dr.

Role: primary

Elena Schlapakow, Dr.

Role: primary

Susanne Petri, Prof. Dr.

Role: primary

Annekathrin Rödiger, Dr.

Role: primary

Clemens Eickhoff, Dr.

Role: primary

Elmar Pinkhardt, Dr.

Role: primary

Moritz Metelmann, Dr.

Role: primary

Julian Großkreutz, Prof. Dr.

Role: primary

Joachim Wolf, Dr.

Role: primary

Paul Lingor, Prof. Dr.

Role: primary

Matthias Böntert, Dr.

Role: primary

Zacharias Kohl, Dr.

Role: primary

Johannes Prudlo, Prof. Dr.

Role: primary

Johannes Dorst, Prof. Dr.

Role: primary

Bertold Schrank, Dr.

Role: primary

Daniel Zeller, Dr.

Role: primary

Other Identifiers

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LIPCAL-ALS II 1.1

Identifier Type: -

Identifier Source: org_study_id