Efficacy and Tolerability of Beta Hydroxybutyrate Ester in Patients With Amyotrophic Lateral Sclerosis (ALS) (KETO-ALS)
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ClinicalTrials.gov Identifier: NCT04820478 |
Recruitment Status :
Recruiting
First Posted : March 29, 2021
Last Update Posted : September 26, 2022
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
Amyotrophic Lateral Sclerosis | Dietary Supplement: Beta Hydroxybutyrate Ester Dietary Supplement: Placebo | Not Applicable |
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 76 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
Masking Description: | placebo-controlled study, using a placebo with similar look and taste in similar bottles; the study is double-blinded, i.e. patients and study personnel are masked |
Primary Purpose: | Treatment |
Official Title: | Efficacy and Tolerability of Beta Hydroxybutyrate Ester in Patients With Amyotrophic Lateral Sclerosis (ALS) |
Actual Study Start Date : | April 1, 2022 |
Estimated Primary Completion Date : | October 1, 2023 |
Estimated Study Completion Date : | October 1, 2023 |

Arm | Intervention/treatment |
---|---|
Experimental: Beta Hydroxybutyrate Ester
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)
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Dietary Supplement: Beta Hydroxybutyrate Ester
see arm/group description |
Placebo Comparator: Placebo
matching placebo, in addition to normal food intake and standard therapy (2 x 50 mg riluzole per day)
|
Dietary Supplement: Placebo
see arm/group description |
- Neurofilament Light Chain [ Time Frame: 6 months ]Neurofilament Light Chain (NfL) serum levels
- Survival [ Time Frame: 6 months ]Survival (time to death or tracheostomy)
- Amyotrophic Lateral Sclerosis Functional Rating Scale Revised [ Time Frame: 6 months ]Amyotrophic Lateral Sclerosis Functional Rating Scale Revised (ALSFRS-R) score, measured as individual slope (loss of points per month)
- Body Mass Index [ Time Frame: 6 months ]Body Mass Index (BMI), weight (in kg) and height (in m) will be combined to report BMI in kg/m^2
- Slow Vital Capacity [ Time Frame: 6 months ]Slow Vital Capacity (sVC)
- Resting Energy Expenditure [ Time Frame: 6 months ]Resting Energy Expenditure (REE), measured by indirect calorimetry
- Fatt mass [ Time Frame: 6 months ]Fat mass (% of total body mass), measured by bioelectrical impedance analysis (BIA)
- Total Body Water [ Time Frame: 6 months ]total body water (% of total body mass), measured by bioelectrical impedance analysis (BIA)
- Muscle Mass [ Time Frame: 6 months ]muscle mass (% of total body mass) measured by bioelectrical impedance analysis (BIA)
- Fat Free Mass [ Time Frame: 6 months ]fat free mass (% of total body mass), measured by bioelectrical impedance analysis (BIA)
- Body Cell Mass [ Time Frame: 6 months ]body cell mass (% of total body mass), measured by bioelectrical impedance analysis (BIA)
- Extracellular Mass [ Time Frame: 6 months ]extracellular mass (% of total body mass), measured by bioelectrical impedance analysis (BIA)
- Lean Body Mass [ Time Frame: 6 months ]lean body mass (% of total body mass), measured by bioelectrical impedance analysis (BIA)
- Individual Quality of Life [ Time Frame: 6 months ]Individual Quality of Life, measured by the Euro Quality of Life (EQ-5D-5L) questionnaire
- Neurofilament Phosphorylated Heavy Chain [ Time Frame: 6 months ]Neurofilament Phosphorylated Heavy Chain (pNfH) in cerebrospinal fluid (CSF)
- Beta Hydroxybutyrate [ Time Frame: 6 months ]Beta Hydroxybutyrate serum levels
- Acetone [ Time Frame: 6 months ]Acetone concentration in urine
- Appetite [ Time Frame: 6 months ]Appetite, measured by the Council of Appetite Questionnaire (CNAQ)
- Eating Habits [ Time Frame: 6 months ]Eating Habits, evaluated by the Ulm Nutrition Questionnaire (UNQ; see LIPCAL study)
- Adverse Events [ Time Frame: 6 months ]Terms and frequencies of Adverse Events (AEs) and Serious Adverse Events (SAEs)

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Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- 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)
Exclusion Criteria:
- hyperinsulinism
- pyruvate decarboxylase deficit
- disturbance of fatty acid oxidation
- disturbance of gluconeogenesis
- acute porphyria
- metabolism disorders which prevent utilization or degradation of ketone bodies
- 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

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04820478
Contact: Johannes Dorst, Prof | +49 731 177 5285 | johannes.dorst@uni-ulm.de |
Germany | |
University of Ulm | Recruiting |
Ulm, Baden-Wurttemberg, Germany, 89081 | |
Contact: Johannes Dorst, Prof +49 731 177 5285 johannes.dorst@uni-ulm.de |
Responsible Party: | Albert Christian Ludolph, Prof., Prof., University of Ulm |
ClinicalTrials.gov Identifier: | NCT04820478 |
Other Study ID Numbers: |
KETO-ALS V 1.41 |
First Posted: | March 29, 2021 Key Record Dates |
Last Update Posted: | September 26, 2022 |
Last Verified: | September 2022 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | Yes |
Plan Description: | 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. |
Supporting Materials: |
Study Protocol |
Time Frame: | 3 months to 5 years following article publication |
Access Criteria: | Data will be shard 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. |
URL: | https://www.uniklinik-ulm.de/neurologie.html |
Studies a U.S. FDA-regulated Drug Product: | No |
Studies a U.S. FDA-regulated Device Product: | No |
nutrition beta hydroxybutyrate ester high-caloric ketone ester |
Motor Neuron Disease Amyotrophic Lateral Sclerosis Sclerosis Pathologic Processes Neurodegenerative Diseases Nervous System Diseases |
Neuromuscular Diseases Spinal Cord Diseases Central Nervous System Diseases TDP-43 Proteinopathies Proteostasis Deficiencies Metabolic Diseases |