Ultra-high-caloric, Fatty Diet in ALS

Amyotrophic Lateral Sclerosis Clinical Trial

— LIPCAL-ALS II  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06280079
• Other study ID #: LIPCAL-ALS II 1.1
• Status: Not yet recruiting
• Phase: N/A
• Start date: May 1, 2024
• Est. completion date: May 1, 2027

Study information

• Verified date: February 2024
• Source: University of Ulm
• Contact: Johannes Dorst, Prof. Dr.
• Phone: +497311775285
• Email: johannes.dorst[@]uni-ulm.de
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

Description:

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 392
• Est. completion date: May 1, 2027
• Est. primary completion date: May 1, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Amyotrophic Lateral Sclerosis
• Motor Neuron Disease
• Sclerosis

Intervention

Dietary Supplement:
• 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

Other:
• Placebo
<5% fat (<3,5g), protein 0g, carbohydrates 0g, fiber 0g

Locations

Country	Name	City	State
Germany	RWTH Aachen	Aachen
Germany	Charité Universitätsmedizin Berlin	Berlin
Germany	University Clinic Bochum	Bochum
Germany	University Clinic Bonn	Bonn
Germany	Technical University Dresden	Dresden
Germany	University Clinic Erlangen	Erlangen
Germany	Alfried Krupp Krankenhaus Essen	Essen
Germany	University Clinic Göttingen	Göttingen
Germany	University Clinic Halle	Halle
Germany	Hannover Medical School	Hannover
Germany	University Clinic Jena	Jena
Germany	DRK Clinic Kassel	Kassel
Germany	Klinikum Kempten	Kempten
Germany	University Clinic Leipzig	Leipzig
Germany	University Clinic Lübeck	Lübeck
Germany	University Clinic Mannheim	Mannheim
Germany	Technical University Munich	Munich
Germany	University Clinic Münster	Münster
Germany	University Clinic Regensburg	Regensburg
Germany	University Clinic Rostock	Rostock
Germany	University of Ulm	Ulm
Germany	DKD HELIOS Clinic Wiesbaden	Wiesbaden
Germany	University Clinic Würzburg	Würzburg

Sponsors (1)

Lead Sponsor	Collaborator
University of Ulm

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Microtubule-associated protein 2 in serum	change of Microtubule-associated protein 2 levels in serum compared to baseline	18 months
Other	Microtubule-associated protein 2 in cerebrospinal fluid	change of microtubule-associated protein 2 levels in cerebrospinal fluid compared to baseline	18 months
Other	Ubiquitin carboxy-terminal hydrolase L1 in serum	change of ubiquitin carboxy-terminal hydrolase L1 levels in serum compared to baseline	18 months
Other	Ubiquitin carboxy-terminal hydrolase L1 in cerebrospinal fluid	change of ubiquitin carboxy-terminal hydrolase L1 levels in cerebrospinal fluid compared to baseline	18 months
Other	Transmembrane glycoprotein NMB in serum	change of transmembrane glycoprotein NMB levels in serum compared to baseline	18 months
Other	Transmembrane glycoprotein NMB in cerebrospinal fluid	change of transmembrane glycoprotein NMB levels in cerebrospinal fluid compared to baseline	18 months
Other	Human cartilage glycoprotein 39 in serum	change of human cartilage glycoprotein 39 levels in serum compared to baseline	18 months
Other	Human cartilage glycoprotein 39 in cerebrospinal fluid	change of human cartilage glycoprotein 39 levels in cerebrospinal fluid compared to baseline	18 months
Other	SNAP-25 in serum	change of SNAP-25 levels in serum compared to baseline	18 months
Other	SNAP-25 in cerebrospinal fluid	change of SNAP-25 levels in cerebrospinal fluid compared to baseline	18 months
Other	Beta-synuclein in serum	change of beta-synuclein levels in serum compared to baseline	18 months
Other	Beta-synuclein in cerebrospinal fluid	change of beta-synuclein levels in cerebrospinal fluid compared to baseline	18 months
Other	Aquaporin-4 in serum	change of aquaporin-4 levels in serum compared to baseline	18 months
Other	Aquaporin-4 in cerebrospinal fluid	change of aquaporin-4 levels in cerebrospinal fluid compared to baseline	18 months
Other	Glial fibrillary acidic protein in serum	change of glial fibrillary acidic protein levels in serum compared to baseline	12 months
Other	Glial fibrillary acidic protein in cerebrospinal fluid	change of glial fibrillary acidic protein levels in cerebrospinal fluid compared to baseline	12 months
Other	Soluble triggering receptor expressed on myeloid cell-1 in serum	change of soluble triggering receptor expressed on myeloid cell-1 levels in serum compared to baseline	12 months
Other	Soluble triggering receptor expressed on myeloid cell-1 in cerebrospinal fluid	change of soluble triggering receptor expressed on myeloid cell-1 levels in cerebrospinal fluid compared to baseline	12 months
Other	CC-chemokine ligand 2 in serum	change of CC-chemokine ligand 2 levels in serum compared to baseline	12 months
Other	CC-chemokine ligand 2 in cerebrospinal fluid	change of CC-chemokine ligand 2 levels in cerebrospinal fluid compared to baseline	12 months
Other	interleukin-1b in serum	change of interleukin-1b levels in serum compared to baseline	12 months
Other	interleukin-1b in cerebrospinal fluid	change of interleukin-1b levels in cerebrospinal fluid compared to baseline	12 months
Other	interleukin-2 in serum	change of interleukin-2 levels in serum compared to baseline	12 months
Other	interleukin-2 in cerebrospinal fluid	change of interleukin-2 levels in cerebrospinal fluid compared to baseline	12 months
Other	interleukin-4 in serum	change of interleukin-4 levels in serum compared to baseline	12 months
Other	interleukin-4 in cerebrospinal fluid	change of interleukin-4 levels in cerebrospinal fluid compared to baseline	12 months
Other	interleukin-6 in serum	change of interleukin-6 levels in serum compared to baseline	12 months
Other	interleukin-6 in cerebrospinal fluid	change of interleukin-6 levels in cerebrospinal fluid compared to baseline	12 months
Other	interleukin-10 in serum	change of interleukin-10 levels in serum compared to baseline	12 months
Other	interleukin-10 in cerebrospinal fluid	change of interleukin-10 levels in cerebrospinal fluid compared to baseline	12 months
Other	interleukin-12p70 in serum	change of interleukin-12p70 levels in serum compared to baseline	12 months
Other	interleukin-12p70 in cerebrospinal fluid	change of interleukin-12p70 levels in cerebrospinal fluid compared to baseline	12 months
Other	interleukin-17 in serum	change of interleukin-17 levels in serum compared to baseline	12 months
Other	interleukin-17 in cerebrospinal fluid	change of interleukin-17 levels in cerebrospinal fluid compared to baseline	12 months
Other	Tumor necrosis factor alpha in serum	change of tumor necrosis factor alpha levels in serum compared to baseline	12 months
Other	Tumor necrosis factor alpha in cerebrospinal fluid	change of tumor necrosis factor alpha levels in cerebrospinal fluid compared to baseline	12 months
Primary	Survival	Time from date of randomization until date of death, tracheostomy, or permanent continous ventilation (>22 hours per day)	18 months
Secondary	Amyotrophic Lateral Sclerosis Functional Rating Scale Revised	Change per month of Amyotrophic Lateral Sclerosis Functional Rating Scale Revised	18 months
Secondary	Rasch Overall Amyotrophic Lateral Sclerosis Disability Scale	Change per month of Rasch Overall Amyotrophic Lateral Sclerosis Disability Scale	18 months
Secondary	Individual Quality of Life	Change of Euro Quality of Life 5D 5L (EQ-5D-5L) compared to baseline	18 months
Secondary	Slow vital capacity	Change of slow vital capacity compared to baseline	18 months
Secondary	Survival	Time from date of randomization until date of death, tracheostomy, or permanent continous ventilation (>22 hours per day)	6 months
Secondary	Survival	Time from date of randomization until date of death, tracheostomy, or permanent continous ventilation (>22 hours per day)	12 months
Secondary	Time to death	Time from date of randomization until date of death	18 months
Secondary	Time to tracheostomy	Time from date of randomization until date of tracheostomy	18 months
Secondary	Time to permanent continous ventilator dependence	Time from date of randomization to permanent continous ventilator dependence (>22 hours per day)	18 month
Secondary	Ventilation assistance-free survival	Time from date of randomization until implementation of mechanical ventilation	18 months
Secondary	Body Mass Index	Change of body mass index compared to baseline	18 months
Secondary	Council of Nutrition Appetite Questionnaire	Change of Council of Nutrition Appetite Questionnaire sum score compared to baseline	18 months
Secondary	Eating Habits	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).	18 months
Secondary	Neurofilament light chain	Change of neurofilament light chain serum levels compared to baseline	18 months
Secondary	Amyotrophic Lateral Sclerosis Functional Rating Scale Revised Prediction Model	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	18 months
Secondary	Neurofilament Assess Score	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	18 months