Amyotrophic Lateral SclerosisKETO-ALSNCT04820478
Efficacy and Tolerability of Beta Hydroxybutyrate Ester in Patients With Amyotrophic Lateral Sclerosis (ALS)
A study testing Beta Hydroxybutyrate Ester (KetoneAid KE4) in people with Amyotrophic Lateral Sclerosis, run by University of Ulm at 1 site in Germany.
Trial summary
Weight loss is a known negative prognostic factor in amyotrophic lateral sclerosis (ALS). One potential mechanism of weight loss in ALS is a disturbance of the mitochondrial complex I which causes an energy deficit in affected cells. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Amyotrophic Lateral Sclerosis
- What is being tested?
- Beta Hydroxybutyrate Ester (KetoneAid KE4)
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 81 participants
- Where
- 1 siteGermany
- Study dates
- 1 Apr 2022to 12 Feb 2025
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Probable (clinically or laboratory) or definite ALS according to the revised version of the El Escorial World Federation of Neurology criteria
- loss of Amyotrophic Lateral Sclerosis Functional Rating Scale Revised (ALSFRS-R) of ≥ 0.33 points per month since onset (first paresis), based on the formula: (48 - score at screening visit) / (months between onset and screening visit)
- age ≥ 18 years
- continuously treated with 100 mg riluzole per day for at least 4 weeks
- capable of thoroughly understanding all information given and giving full informed consent according to good clinical practice (GCP)
Who cannot join
- hyperinsulinism
- pyruvate decarboxylase deficit
- disturbance of fatty acid oxidation
- disturbance of gluconeogenesis
- acute porphyria
- metabolism disorders which prevent utilization or degradation of ketone bodies
Show all 17Show fewer
- severe gastro-esophageal reflux
- renal insufficiency (medical history and/or elevated serum creatinine levels and/or glomerular filtration rate (GFR) <90 ml/min
- previous participation in another interventional study within the preceding 4 weeks
- tracheostomy
- pregnancy or breast-feeding females
- evidence of a major psychiatric disorder or clinically evident dementia
- intake of diuretics
- severe dysphagia
- nutrition via percutaneous endoscopic gastrostomy (PEG)
- electrolyte or acid-base imbalance
- heart failure New York Heart Association (NYHA) II or above
Trial locations and contacts
1 site in 1 country.
About this study
Weight loss is a known negative prognostic factor in amyotrophic lateral sclerosis (ALS). One potential mechanism of weight loss in ALS is a disturbance of the mitochondrial complex I which causes an energy deficit in affected cells. Over the last years, various interventional studies targeting the energy deficit in ALS yielded promising results; however,it is still unclear which kind of nutrition or nutritional supplement is most beneficial. Ketone bodies represent a logical therapeutic option in ALS as ketone bodies are an extremely high-energetic substrate which yields the double amount of adenosine triphosphate (ATP) per mole compared to glucose. The human liver is able to synthesize ketone bodies (beta-hydroxybutyrate, acetone, and aceto-acetate) from fat in times of glucose shortage, for example after a prolonged period of fasting. This metabolic shift is the underlying principle of the ketogenic diet, a carbohydrate-free, fat-rich diet which has been successfully tested in other neurodegenerative diseases such as Alzheimer's and Parkinson's disease. In the ALS mouse model, a ketogenic diet was associated with a slower decline of motor function. However, a ketogenic diet is difficult to implement in ALS as it requires a long-term change of eating habits, which is difficult to achieve due to progressive dysphagia, fast worsening of general condition, and limited survival. Therefore, the direct administration of ketone bodies yields a more realistic alternative in ALS as it is easy to apply and allows to maintain the usual eating habits. In this study, we hypothesize that the administration of 3 x 10 g beta hydroxybutyrate ester per day (in addition to normal food intake and the standard medication of 2 x 50 mg riluzole) slows down disease progression as measured by neurofilament light chains (NfL) in serum after 6 months compared to placebo. Power calculation relies on the results of the lipids and calories for ALS (LIPCAL-ALS) study which tested the effect of a high-caloric fatty nutritional supplement in ALS. The study revealed that NfL serum values declined significantly in the intervention group while remaining stable in the placebo group over the course of the study. Assuming a similar effect size for ketone bodies, we calculated that 76 patients had to be included in the current trial.
- Conditions
- Amyotrophic Lateral Sclerosis
- Being tested
- Beta Hydroxybutyrate Ester (KetoneAid KE4), Placebo
- Keywords
- nutrition, beta hydroxybutyrate ester, high-caloric, ketone ester, ketone monoester
- Medical subject headings
- Amyotrophic Lateral Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Beta Hydroxybutyrate Ester (KetoneAid KE4)Dietary supplement
see arm/group description
PlaceboDietary supplement
see arm/group description
| Study group | Role | What they receive |
|---|---|---|
| Beta Hydroxybutyrate Ester | Experimental | 3 x 10 g beta hydroxybutyrate ester per day, in addition to normal food intake and standard therapy (2 x 50 mg riluzole per day) Receives: Dietary Supplement: Beta Hydroxybutyrate Ester (KetoneAid KE4) |
| Placebo | Placebo comparator | matching placebo, in addition to normal food intake and standard therapy (2 x 50 mg riluzole per day) Receives: Dietary Supplement: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Neurofilament Light Chain
Neurofilament Light Chain (NfL) serum levels
Measured: 6 months
Secondary outcomes (19)
Survival
Survival (time to death or tracheostomy)
Measured: 6 months
Amyotrophic Lateral Sclerosis Functional Rating Scale Revised
Amyotrophic Lateral Sclerosis Functional Rating Scale Revised (ALSFRS-R) score, measured as individual slope (loss of points per month)
Measured: 6 months
Body Mass Index
Body Mass Index (BMI), weight (in kg) and height (in m) will be combined to report BMI in kg/m^2
Measured: 6 months
Slow Vital Capacity
Slow Vital Capacity (sVC)
Measured: 6 months
Resting Energy Expenditure
Resting Energy Expenditure (REE), measured by indirect calorimetry
Measured: 6 months
Fatt mass
Fat mass (% of total body mass), measured by bioelectrical impedance analysis (BIA)
Measured: 6 months
Total Body Water
total body water (% of total body mass), measured by bioelectrical impedance analysis (BIA)
Measured: 6 months
Muscle Mass
muscle mass (% of total body mass) measured by bioelectrical impedance analysis (BIA)
Measured: 6 months
Fat Free Mass
fat free mass (% of total body mass), measured by bioelectrical impedance analysis (BIA)
Measured: 6 months
Body Cell Mass
body cell mass (% of total body mass), measured by bioelectrical impedance analysis (BIA)
Measured: 6 months
Extracellular Mass
extracellular mass (% of total body mass), measured by bioelectrical impedance analysis (BIA)
Measured: 6 months
Lean Body Mass
lean body mass (% of total body mass), measured by bioelectrical impedance analysis (BIA)
Measured: 6 months
Individual Quality of Life
Individual Quality of Life, measured by the Euro Quality of Life (EQ-5D-5L) questionnaire
Measured: 6 months
Neurofilament Phosphorylated Heavy Chain
Neurofilament Phosphorylated Heavy Chain (pNfH) in cerebrospinal fluid (CSF)
Measured: 6 months
Beta Hydroxybutyrate
Beta Hydroxybutyrate serum levels
Measured: 6 months
Acetone
Acetone concentration in urine
Measured: 6 months
Appetite
Appetite, measured by the Council of Appetite Questionnaire (CNAQ)
Measured: 6 months
Eating Habits
Eating Habits, evaluated by the Ulm Nutrition Questionnaire (UNQ; see LIPCAL study)
Measured: 6 months
Adverse Events
Terms and frequencies of Adverse Events (AEs) and Serious Adverse Events (SAEs)
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Mar 2021
- Study start1 Apr 2022
- Primary completion12 Feb 2025
- Study completion12 Feb 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (15)Papers the sponsor has linked to this study.
- Other trials for Amyotrophic Lateral SclerosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 81 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Ulm
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Albert Christian Ludolph, Prof., University of Ulm
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04820478
- Sponsor's protocol ID
- KETO-ALS V 1.41
- Acronym
- KETO-ALS
- Status last verified
- Apr 2026
- First submitted
- 24 Mar 2021
- Last updated
- 1 May 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual participant data after de-identification as well as the study protocol will be available. Data will be available beginning 3 months and ending 5 years following article publication. Data will be shared with researchers who provide a methodologically sound proposal. Data will be shared for analyses to achieve the aims provided 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 access agreement.
Publications
Brooks BR, Miller RG, Swash M, Munsat TL; World Federation of Neurology Research Group on Motor Neuron Diseases. El Escorial revisited: revised criteria for the diagnosis of amyotrophic lateral sclerosis. Amyotroph Lateral Scler Other Motor Neuron Disord. 2000 Dec;1(5):293-9. doi: 10.1080/146608200300079536. No abstract available.
PubMed 11464847Dupuis L, Oudart H, Rene F, Gonzalez de Aguilar JL, Loeffler JP. Evidence for defective energy homeostasis in amyotrophic lateral sclerosis: benefit of a high-energy diet in a transgenic mouse model. Proc Natl Acad Sci U S A. 2004 Jul 27;101(30):11159-64. doi: 10.1073/pnas.0402026101. Epub 2004 Jul 19.
PubMed 15263088Desport JC, Preux PM, Truong TC, Vallat JM, Sautereau D, Couratier P. Nutritional status is a prognostic factor for survival in ALS patients. Neurology. 1999 Sep 22;53(5):1059-63. doi: 10.1212/wnl.53.5.1059.
PubMed 10496266Desport JC, Preux PM, Magy L, Boirie Y, Vallat JM, Beaufrere B, Couratier P. Factors correlated with hypermetabolism in patients with amyotrophic lateral sclerosis. Am J Clin Nutr. 2001 Sep;74(3):328-34. doi: 10.1093/ajcn/74.3.328.
PubMed 11522556Dorst J, Cypionka J, Ludolph AC. High-caloric food supplements in the treatment of amyotrophic lateral sclerosis: a prospective interventional study. Amyotroph Lateral Scler Frontotemporal Degener. 2013 Dec;14(7-8):533-6. doi: 10.3109/21678421.2013.823999. Epub 2013 Aug 14.
PubMed 23944684Wills AM, Hubbard J, Macklin EA, Glass J, Tandan R, Simpson EP, Brooks B, Gelinas D, Mitsumoto H, Mozaffar T, Hanes GP, Ladha SS, Heiman-Patterson T, Katz J, Lou JS, Mahoney K, Grasso D, Lawson R, Yu H, Cudkowicz M; MDA Clinical Research Network. Hypercaloric enteral nutrition in patients with amyotrophic lateral sclerosis: a randomised, double-blind, placebo-controlled phase 2 trial. Lancet. 2014 Jun 14;383(9934):2065-2072. doi: 10.1016/S0140-6736(14)60222-1. Epub 2014 Feb 28.
PubMed 24582471Dorst J, Schuster J, Dreyhaupt J, Witzel S, Weishaupt JH, Kassubek J, Weiland U, Petri S, Meyer T, Grehl T, Hermann A, Jordan B, Grosskreutz J, Zeller D, Boentert M, Schrank B, Prudlo J, Winkler AS, Gorbulev S, Roselli F, Dupuis L, Otto M, Ludolph AC. Effect of high-caloric nutrition on serum neurofilament light chain levels in amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry. 2020 Sep;91(9):1007-1009. doi: 10.1136/jnnp-2020-323372. Epub 2020 Aug 11. No abstract available.
PubMed 32788256Steinacker P, Feneberg E, Weishaupt J, Brettschneider J, Tumani H, Andersen PM, von Arnim CA, Bohm S, Kassubek J, Kubisch C, Lule D, Muller HP, Muche R, Pinkhardt E, Oeckl P, Rosenbohm A, Anderl-Straub S, Volk AE, Weydt P, Ludolph AC, Otto M. Neurofilaments in the diagnosis of motoneuron diseases: a prospective study on 455 patients. J Neurol Neurosurg Psychiatry. 2016 Jan;87(1):12-20. doi: 10.1136/jnnp-2015-311387. Epub 2015 Aug 21.
PubMed 26296871Grammatikopoulou MG, Goulis DG, Gkiouras K, Theodoridis X, Gkouskou KK, Evangeliou A, Dardiotis E, Bogdanos DP. To Keto or Not to Keto? A Systematic Review of Randomized Controlled Trials Assessing the Effects of Ketogenic Therapy on Alzheimer Disease. Adv Nutr. 2020 Nov 16;11(6):1583-1602. doi: 10.1093/advances/nmaa073.
PubMed 32597927Phillips MCL, Murtagh DKJ, Gilbertson LJ, Asztely FJS, Lynch CDP. Low-fat versus ketogenic diet in Parkinson's disease: A pilot randomized controlled trial. Mov Disord. 2018 Aug;33(8):1306-1314. doi: 10.1002/mds.27390. Epub 2018 Aug 11.
PubMed 30098269Zhao Z, Lange DJ, Voustianiouk A, MacGrogan D, Ho L, Suh J, Humala N, Thiyagarajan M, Wang J, Pasinetti GM. A ketogenic diet as a potential novel therapeutic intervention in amyotrophic lateral sclerosis. BMC Neurosci. 2006 Apr 3;7:29. doi: 10.1186/1471-2202-7-29.
PubMed 16584562Clarke K, Tchabanenko K, Pawlosky R, Carter E, Todd King M, Musa-Veloso K, Ho M, Roberts A, Robertson J, Vanitallie TB, Veech RL. Kinetics, safety and tolerability of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate in healthy adult subjects. Regul Toxicol Pharmacol. 2012 Aug;63(3):401-8. doi: 10.1016/j.yrtph.2012.04.008. Epub 2012 May 3.
PubMed 22561291Stubbs BJ, Cox PJ, Evans RD, Santer P, Miller JJ, Faull OK, Magor-Elliott S, Hiyama S, Stirling M, Clarke K. On the Metabolism of Exogenous Ketones in Humans. Front Physiol. 2017 Oct 30;8:848. doi: 10.3389/fphys.2017.00848. eCollection 2017.
PubMed 29163194Poffe C, Ramaekers M, Van Thienen R, Hespel P. Ketone ester supplementation blunts overreaching symptoms during endurance training overload. J Physiol. 2019 Jun;597(12):3009-3027. doi: 10.1113/JP277831. Epub 2019 May 22.
PubMed 31039280Hashim SA, VanItallie TB. Ketone body therapy: from the ketogenic diet to the oral administration of ketone ester. J Lipid Res. 2014 Sep;55(9):1818-26. doi: 10.1194/jlr.R046599. Epub 2014 Mar 5.
PubMed 24598140
Study at a glance
From the registry record, last updated by the sponsor on 1 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Tolerability of Beta Hydroxybutyrate Ester in Patients With Amyotrophic Lateral Sclerosis (ALS)
- ClinicalTrials.gov ID
- NCT04820478
- Acronym / sponsor ID
- KETO-ALS / KETO-ALS V 1.41
- Conditions
- Amyotrophic Lateral Sclerosis
- Keywords
- nutrition, beta hydroxybutyrate ester, high-caloric, ketone ester, ketone monoester
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 81 participants (actual)
- Lead sponsor
- University of UlmUniversity, hospital or other
- Study start
- 1 Apr 2022 (actual)
- Primary completion
- 12 Feb 2025 (actual)
- Study completion
- 12 Feb 2025 (actual)
- First posted
- 29 Mar 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Weight loss is a known negative prognostic factor in amyotrophic lateral sclerosis (ALS). One potential mechanism of weight loss in ALS is a disturbance of the mitochondrial complex I which causes an energy deficit in affected cells. Over the last years, various interventional studies targeting the energy deficit in ALS yielded promising results; however,it is still unclear which kind of nutrition or nutritional supplement is most beneficial. Ketone bodies represent a logical therapeutic option in ALS as ketone bodies are an extremely high-energetic substrate which yields the double amount of adenosine triphosphate (ATP) per mole compared to glucose. The human liver is able to synthesize ketone bodies (beta-hydroxybutyrate, acetone, and aceto-acetate) from fat in times of glucose shortage, for example after a prolonged period of fasting. This metabolic shift is the underlying principle of the ketogenic diet, a carbohydrate-free, fat-rich diet which has been successfully tested in other neurodegenerative diseases such as Alzheimer's and Parkinson's disease. In the ALS mouse model, a ketogenic diet was associated with a slower decline of motor function. However, a ketogenic diet is difficult to implement in ALS as it requires a long-term change of eating habits, which is difficult to achieve due to progressive dysphagia, fast worsening of general condition, and limited survival. Therefore, the direct administration of ketone bodies yields a more realistic alternative in ALS as it is easy to apply and allows to maintain the usual eating habits. In this study, we hypothesize that the administration of 3 x 10 g beta hydroxybutyrate ester per day (in addition to normal food intake and the standard medication of 2 x 50 mg riluzole) slows down disease progression as measured by neurofilament light chains (NfL) in serum after 6 months compared to placebo. Power calculation relies on the results of the lipids and calories for ALS (LIPCAL-ALS) study which tested the effect of a high-caloric fatty nutritional supplement in ALS. The study revealed that NfL serum values declined significantly in the intervention group while remaining stable in the placebo group over the course of the study. Assuming a similar effect size for ketone bodies, we calculated that 76 patients had to be included in the current trial.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Beta Hydroxybutyrate Ester | Experimental | Dietary Supplement: Beta Hydroxybutyrate Ester (KetoneAid KE4)3 x 10 g beta hydroxybutyrate ester per day, in addition to normal food intake and standard therapy (2 x 50 mg riluzole per day) |
| Placebo | Placebo comparator | Dietary Supplement: Placebomatching placebo, in addition to normal food intake and standard therapy (2 x 50 mg riluzole per day) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Probable (clinically or laboratory) or definite ALS according to the revised version of the El Escorial World Federation of Neurology criteria
- loss of Amyotrophic Lateral Sclerosis Functional Rating Scale Revised (ALSFRS-R) of ≥ 0.33 points per month since onset (first paresis), based on the formula: (48 - score at screening visit) / (months between onset and screening visit)
- age ≥ 18 years
- continuously treated with 100 mg riluzole per day for at least 4 weeks
- capable of thoroughly understanding all information given and giving full informed consent according to good clinical practice (GCP)
Key exclusion criteria (17 listed)
- hyperinsulinism
- pyruvate decarboxylase deficit
- disturbance of fatty acid oxidation
- disturbance of gluconeogenesis
- acute porphyria
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Beta Hydroxybutyrate Ester (KetoneAid KE4)see arm/group description | Dietary supplement | Beta Hydroxybutyrate Ester |
| Placebosee arm/group description | Dietary supplement | Placebo |
Primary outcome
Neurofilament Light Chain
Time frame: 6 months
Neurofilament Light Chain (NfL) serum levels
19 secondary outcomes
Survival
Time frame: 6 months
Amyotrophic Lateral Sclerosis Functional Rating Scale Revised
Time frame: 6 months
Body Mass Index
Time frame: 6 months
Slow Vital Capacity
Time frame: 6 months
Resting Energy Expenditure
Time frame: 6 months
Fatt mass
Time frame: 6 months
Total Body Water
Time frame: 6 months
Muscle Mass
Time frame: 6 months
Fat Free Mass
Time frame: 6 months
Body Cell Mass
Time frame: 6 months
Extracellular Mass
Time frame: 6 months
Lean Body Mass
Time frame: 6 months
Individual Quality of Life
Time frame: 6 months
Neurofilament Phosphorylated Heavy Chain
Time frame: 6 months
Beta Hydroxybutyrate
Time frame: 6 months
Acetone
Time frame: 6 months
Appetite
Time frame: 6 months
Eating Habits
Time frame: 6 months
Adverse Events
Time frame: 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 May 2026.
- Background: PubMed 11464847Brooks BR, Miller RG, Swash M, Munsat TL; World Federation of Neurology Research Group on Motor Neuron Diseases. El Escorial revisited: revised criteria for the diagnosis of amyotrophic lateral sclerosis. Amyotroph Lateral Scler Other Motor Neuron Disord. 2000 Dec;1(5):293-9. doi: 10.1080/146608200300079536. No abstract available.
- Background: PubMed 15263088Dupuis L, Oudart H, Rene F, Gonzalez de Aguilar JL, Loeffler JP. Evidence for defective energy homeostasis in amyotrophic lateral sclerosis: benefit of a high-energy diet in a transgenic mouse model. Proc Natl Acad Sci U S A. 2004 Jul 27;101(30):11159-64. doi: 10.1073/pnas.0402026101. Epub 2004 Jul 19.
- Background: PubMed 10496266Desport JC, Preux PM, Truong TC, Vallat JM, Sautereau D, Couratier P. Nutritional status is a prognostic factor for survival in ALS patients. Neurology. 1999 Sep 22;53(5):1059-63. doi: 10.1212/wnl.53.5.1059.
- Background: PubMed 11522556Desport JC, Preux PM, Magy L, Boirie Y, Vallat JM, Beaufrere B, Couratier P. Factors correlated with hypermetabolism in patients with amyotrophic lateral sclerosis. Am J Clin Nutr. 2001 Sep;74(3):328-34. doi: 10.1093/ajcn/74.3.328.
- Background: PubMed 23944684Dorst J, Cypionka J, Ludolph AC. High-caloric food supplements in the treatment of amyotrophic lateral sclerosis: a prospective interventional study. Amyotroph Lateral Scler Frontotemporal Degener. 2013 Dec;14(7-8):533-6. doi: 10.3109/21678421.2013.823999. Epub 2013 Aug 14.
- Background: PubMed 24582471Wills AM, Hubbard J, Macklin EA, Glass J, Tandan R, Simpson EP, Brooks B, Gelinas D, Mitsumoto H, Mozaffar T, Hanes GP, Ladha SS, Heiman-Patterson T, Katz J, Lou JS, Mahoney K, Grasso D, Lawson R, Yu H, Cudkowicz M; MDA Clinical Research Network. Hypercaloric enteral nutrition in patients with amyotrophic lateral sclerosis: a randomised, double-blind, placebo-controlled phase 2 trial. Lancet. 2014 Jun 14;383(9934):2065-2072. doi: 10.1016/S0140-6736(14)60222-1. Epub 2014 Feb 28.
- Background: PubMed 32788256Dorst J, Schuster J, Dreyhaupt J, Witzel S, Weishaupt JH, Kassubek J, Weiland U, Petri S, Meyer T, Grehl T, Hermann A, Jordan B, Grosskreutz J, Zeller D, Boentert M, Schrank B, Prudlo J, Winkler AS, Gorbulev S, Roselli F, Dupuis L, Otto M, Ludolph AC. Effect of high-caloric nutrition on serum neurofilament light chain levels in amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry. 2020 Sep;91(9):1007-1009. doi: 10.1136/jnnp-2020-323372. Epub 2020 Aug 11. No abstract available.
- Background: PubMed 26296871Steinacker P, Feneberg E, Weishaupt J, Brettschneider J, Tumani H, Andersen PM, von Arnim CA, Bohm S, Kassubek J, Kubisch C, Lule D, Muller HP, Muche R, Pinkhardt E, Oeckl P, Rosenbohm A, Anderl-Straub S, Volk AE, Weydt P, Ludolph AC, Otto M. Neurofilaments in the diagnosis of motoneuron diseases: a prospective study on 455 patients. J Neurol Neurosurg Psychiatry. 2016 Jan;87(1):12-20. doi: 10.1136/jnnp-2015-311387. Epub 2015 Aug 21.
- Background: PubMed 32597927Grammatikopoulou MG, Goulis DG, Gkiouras K, Theodoridis X, Gkouskou KK, Evangeliou A, Dardiotis E, Bogdanos DP. To Keto or Not to Keto? A Systematic Review of Randomized Controlled Trials Assessing the Effects of Ketogenic Therapy on Alzheimer Disease. Adv Nutr. 2020 Nov 16;11(6):1583-1602. doi: 10.1093/advances/nmaa073.
- Background: PubMed 30098269Phillips MCL, Murtagh DKJ, Gilbertson LJ, Asztely FJS, Lynch CDP. Low-fat versus ketogenic diet in Parkinson's disease: A pilot randomized controlled trial. Mov Disord. 2018 Aug;33(8):1306-1314. doi: 10.1002/mds.27390. Epub 2018 Aug 11.
- Background: PubMed 16584562Zhao Z, Lange DJ, Voustianiouk A, MacGrogan D, Ho L, Suh J, Humala N, Thiyagarajan M, Wang J, Pasinetti GM. A ketogenic diet as a potential novel therapeutic intervention in amyotrophic lateral sclerosis. BMC Neurosci. 2006 Apr 3;7:29. doi: 10.1186/1471-2202-7-29.
- Background: PubMed 22561291Clarke K, Tchabanenko K, Pawlosky R, Carter E, Todd King M, Musa-Veloso K, Ho M, Roberts A, Robertson J, Vanitallie TB, Veech RL. Kinetics, safety and tolerability of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate in healthy adult subjects. Regul Toxicol Pharmacol. 2012 Aug;63(3):401-8. doi: 10.1016/j.yrtph.2012.04.008. Epub 2012 May 3.
- Individual participant dataSharing planned: Yes. Individual participant data after de-identification as well as the study protocol will be available. Data will be available beginning 3 months and ending 5 years following article publication. Data will be shared with researchers who provide a methodologically sound proposal. Data will be shared for analyses to achieve the aims provided 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 access agreement.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Beta Hydroxybutyrate Ester (KetoneAid KE4) in people with Amyotrophic Lateral Sclerosis, run by University of Ulm at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Neurofilament Light Chain (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04820478, which also lists 15 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 May 2026.