Clinical trial NCT04461821: Exhaled Breath Analysis by Secondary Electrospray Ionization - Mass Spectrometry in Children and Adolescents
Official title: Exhaled Breath Analysis by Secondary Electrospray Ionization - Mass Spectrometry in Children and Adolescents (EBECA)
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Respiratory Diseases
Neurological Disorders
Type 1 Diabetes
Keywords: Exhaled breath analysis
Therapeutic drug monitoring (TDM)
Secondary Electrospray ionization - mass spectrometry (SESI-MS)
breath analysis platform
breath metabolomics
Lead sponsor: University Children's Hospital Basel
Sponsor class: OTHER
Collaborators: name: Swiss National Science Foundation
name: Fondation Botnar (Switzerland)
First posted: 2020-07-08
Enrollment: 3600
Sex: ALL
Maximum age (years): 22
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Participants presenting with an acute disease in the emergency department at the University of Basel Children's Hospital (UKBB).

Participants with chronic diseases recorded at the University of Basel Children's Hospital (UKBB).

Brief summary: This study is to investigate breath analysis (breath metabolomics) combined with established bioinformatic tools as a platform for companion diagnostics.

Detailed description: Therapeutic drug monitoring (TDM) is defined as measuring concentrations of a drug at one or more time points in a biological matrix after a dose. The purpose of TDM is to individualize the drug dose to achieve maximum efficacy and at the same time minimize toxicity. The concept of TDM could potentially be even more valuable if in addition to drug concentrations, other drug-regulated and drug-related metabolites could be included in the models to define optimal dosage. There exists a clinical need to stratify patients with better precision to improve current clinical and therapeutic management. Breath analysis offers an opportunity to non-invasively retrieve relevant information on the ongoing internal biochemical processes, as well as to monitor the respiratory system itself. For breath analysis, a Secondary Electrospray ionization - mass spectrometry (SESI-MS) breath analysis platform will be used to capture disease-related, drug-regulated and drug-related metabolites (breath metabolomics) in exhaled breath. This information, retrieved in parallel to standard of care clinical co-variates, could have the potential to provide a more personalized therapeutic management of patients.

Eligibility criteria: Inclusion Criteria:

* Age 0 ≤ 22 years at study entry and signed informed consent

Additional inclusion criteria for respiratory disease population:

* Acute disease: - Acute signs for a respiratory disease, indicated by e.g. increased work of breathing (e.g. dyspnea, increased respiratory rate), cough or wheezing.
* Chronic disease: - Suspected or confirmed chronic airway disease (e.g. asthma).

Additional inclusion criteria for neurological disease population:

* Acute disease: - Acute presentation or report within 24 hours of any signs of neurological deficit (motor function, sensoneural, or verbal).
* Chronic disease: - Confirmed chronic neurologic disease (e.g. childhood epilepsy).

Additional inclusion criteria for T1D disease population:

* Acute disease: - Hyperglycemia and/or pH (venous) \<7.3, bicarbonate \>10 mmol/L, increased levels of acetone in blood or urine in the context of newly diagnosed or known T1D.
* Chronic disease: - Confirmed diagnosis of T1D

Exclusion Criteria:

* Physical or intellectual impairment precluding protocol adherence.

Additional exclusion criteria for respiratory disease population:

* Known malignancy, active smoker (passive smoke exposure is not an exclusion criterium), known inflammatory diseases (e.g. autoimmune disease) that require medical and/or pharmacological treatment and is associated with an inflammatory response, relevant congenital defects

Additional exclusion criteria for neurological disease population:

* Known malignancy, active smoker (passive smoke exposure is not an exclusion criterium), known inflammatory diseases (e.g. autoimmune disease) that require medical and/or pharmacological treatment and is associated with an inflammatory response, relevant congenital defects.

Additional exclusion criteria for T1D population:

* Known malignancy, active smoker (passive smoke exposure is not an exclusion criterium), relevant congenital defects.

Primary outcomes:
measure: Days of hospitalization
timeFrame: approx 30 days (from beginn hospitalisation to discharge date)
measure: Change in Mass spectrometric profile of exhaled breath patterns
timeFrame: Week 0 (first regular clinic visit) to Follow-up visits (approx. years 1-10)
measure: Change in Concentration of exhaled metabolites of pharmacotherapy
timeFrame: Week 0 (first regular clinic visit) to Follow-up visits (approx. years 1-10)
Secondary outcomes:
measure: Identification of chemical structure of exhaled molecules (acetone, glucose)
timeFrame: approx 30 days (from begin hospitalisation to discharge date)
measure: Correlations of identified molecules (acetone, glucose) in exhaled breath with body fluids (blood, saliva, urine) for T1D acute disease (mmol/l)
timeFrame: 0h, 2h, 4h, 6h, 8h, 12h, 18h, 24h, 36h, 48h, 72h (h =hours after hospital admission)
measure: Change in clinical endpoint lung function (Forced Expiratory Pressure in 1 Second FEV1 l/s) for correlation between clinical endpoint and the abundance of exhaled metabolites
timeFrame: approx 10 years (from begin hospitalisation to discharge date and from first regular clinic visit to Follow-up visits)
measure: Change in clinical endpoint (body temperature, Celsius) for correlation between clinical endpoint and the abundance of exhaled metabolites
timeFrame: approx 10 years (from begin hospitalisation to discharge date and from first regular clinic visit to Follow-up visits)
measure: Change in clinical endpoint (blood pressure, mmHg) for correlation between clinical endpoint and the abundance of exhaled metabolites
timeFrame: approx 10 years (from begin hospitalisation to discharge date and from first regular clinic visit to Follow-up visits)
Other outcomes:
Locations:
city: Basel
country: Switzerland
facility: University Children's Hospital Basel (UKBB)
Study officials:
affiliation: University Children's Hospital Basel, UKBB
name: Pablo Sinues, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References: