Metabolites in Blood and Breath in Metabolic Conditions

Measurement of Metabolites in the Breath and Blood in Patients With Altered Metabolism and Healthy Individuals

In patients with inborn errors of metabolism (IEM) and in those requiring a ketogenic diet for the treatment of medical conditions, relevant biochemical analytes are routinely and regularly measured in venous or capillary blood samples. Repeated venipuncture for blood collection is invasive, burdensome, and resource-intensive. As an alternative, capillary blood sampling can provide some relief for the measurement of a limited number of metabolites. Nevertheless, the frequent finger pricks required to obtain capillary blood samples can still be uncomfortable for patients. Therefore, patients could benefit if non-invasive breath measurements were to replace the currently invasive biochemical monitoring methods in the future.

In this study, the usability of metabolite measurements across matrices (venous blood, capillary blood, breath captured by a handheld sensor and breath in a collection bag) in IEM patients, individuals prescribed special health-related diets, and healthy volunteers will be investigated. The usability of a handheld breath sensor for remote monitoring of patients will also be tested. Lastly, exploratory investigations will be performed to identify new disease biomarkers in breath.

Study Overview

• Status: Not yet recruiting
• Conditions: Inborn Errors of Metabolism; Epilepsy (Treatment Refractory)
• Intervention / Treatment: Other: Observational Study

• Study Type: Observational
• Enrollment (Estimated): 100

Contacts and Locations

• Study Contact: Name: Johannes Häberle; Phone Number: +41 44 249 59 88; Email: Johannes.Haeberle@kispi.uzh.ch

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Patients who are routinely cared for at the study site will be invited to participate. Healthy volunteers will be recruited through communication with healthy family members accompanying patients to hospital visits and the general population through flyers.

Description

Inclusion Criteria:

• Patients aged 4-20 years old with refractory epilepsy on a ketogenic diet, or
• Patients aged 4 years old and above with a confirmed diagnosis of urea cycle disorders, organic acidurias, amino acidopathies and fatty acid oxidation defects, or
• healthy adults and
• informed consent

Exclusion Criteria:

• Physical findings at screening that would compromise safety of the participant or quality of study data. Examples include presentation of fever, pulmonary complications, presence of disease comorbidities that might interfere with study result and inability to comply with study procedures.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients or healthy adult volunteers	Other: Observational Study; no intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Concentration (μmol/L) of metabolites of clinical interest in venous blood, capillary blood and breath of participants.	Concentration of beta-hydroxybutyrate in venous and capillary blood; Concentration of acetone in exhaled breath; Concentration of ammonia in venous blood and exhaled breath; Concentration of amino acids (alanine, arginine, asparagine, aspartic acid, citrulline, cysteine, glutamine, glutamic acid, glycine, histidine, isoleucine, leucine, lysine, methionine, ornithine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine and valine) in venous blood, capillary blood and exhaled breath.	2 hours to 2 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation of metabolite concentrations in different matrices	Correlation between concentration of beta-hydroxybutyrate in venous and capillary blood and concentration of acetone in exhaled breath captured directly by a handheld device with a chemiresistor sensor and breath captured in a collection bag and measured by mass spectrometry; Correlation between concentration of ammonia in venous blood and exhaled breath captured directly by a handheld device with a chemiresistor sen; Correlation between concentration of amino acids in venous and capillary blood and in exhaled breath captured directly by a handheld device with a chemiresistor sensor and breath captured in a collection bag and measured by mass spectrometry	2 hours to 2 weeks
Participant self-report questionnaire on a 4-point Likert scale on the burden of each sampling method	Likert scale: 1, Strongly Agree. 2, Agree. 3, Disagree. 4, Strongly Disagree. The lower the score, the lower the burden of sampling method.	2 hours to 2 weeks
Participant self-report questionnaire on a 4-point Likert scale on the usability of the handheld breath sensor for remote measurements of metabolites	Likert scale: 1, Strongly Agree. 2, Agree. 3, Disagree. 4, Strongly Disagree. The lower the score, the higher the acceptance of using the handheld breath sensor.	2 hours to 2 weeks
Untargeted SESI-based mass spectrometry analysis of exhaled breath captured in a bag	abundance (parts per million) of all detectable and identifiable metabolites in exhaled breath	2 hours

Collaborators and Investigators

• Sponsor: University Children's Hospital, Zurich
• Collaborators: ETH Zurich (Switzerland)

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2026
• Primary Completion (Estimated): October 1, 2036
• Study Completion (Estimated): October 1, 2037

Study Registration Dates

• First Submitted: July 2, 2026
• First Submitted That Met QC Criteria: July 9, 2026
• First Posted (Actual): July 15, 2026

Study Record Updates

• Last Update Posted (Actual): July 15, 2026
• Last Update Submitted That Met QC Criteria: July 9, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Metabolic Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Epilepsy; Metabolism, Inborn Errors; Investigative Techniques; Methods; Observation
• Other Study ID Numbers: 2026-00730

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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