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Exhaled Breath Analysis by Secondary Electrospray Ionization - Mass Spectrometry in Children and Adolescents

Recruiting
Conditions
Respiratory Diseases
Type 1 Diabetes
Neurological Disorders
Interventions
Diagnostic Test: Real-time SESI-MS breath analysis
Diagnostic Test: Off-line breath analysis
Diagnostic Test: Blood analysis
Diagnostic Test: Saliva analysis
Diagnostic Test: Urine analysis
Registration Number
NCT04461821
Lead Sponsor
University Children's Hospital Basel
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.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
3600
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.

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
pneumoniaOff-line breath analysis-
obstructive bronchitis/bronchiolitisBlood analysis-
asthmaBlood analysis-
neurological diseasesOff-line breath analysis-
type 1 diabetes (T1D)Real-time SESI-MS breath analysis-
obstructive bronchitis/bronchiolitisOff-line breath analysis-
pharmacotherapy with antiviral medicationBlood analysis-
pharmacotherapy with antiepileptic medicationReal-time SESI-MS breath analysis-
obstructive bronchitis/bronchiolitisReal-time SESI-MS breath analysis-
pneumoniaReal-time SESI-MS breath analysis-
neurological diseasesReal-time SESI-MS breath analysis-
pneumoniaBlood analysis-
asthmaOff-line breath analysis-
type 1 diabetes (T1D)Urine analysis-
pharmacotherapy with bronchodilatorsOff-line breath analysis-
asthmaReal-time SESI-MS breath analysis-
neurological diseasesBlood analysis-
type 1 diabetes (T1D)Saliva analysis-
pharmacotherapy with antibioticsReal-time SESI-MS breath analysis-
type 1 diabetes (T1D)Off-line breath analysis-
pharmacotherapy with bronchodilatorsReal-time SESI-MS breath analysis-
pharmacotherapy with antibioticsBlood analysis-
type 1 diabetes (T1D)Blood analysis-
pharmacotherapy with bronchodilatorsBlood analysis-
pharmacotherapy with antibioticsOff-line breath analysis-
pharmacotherapy with antiviral medicationOff-line breath analysis-
pharmacotherapy with antifungal medicationReal-time SESI-MS breath analysis-
pharmacotherapy with antiviral medicationReal-time SESI-MS breath analysis-
pharmacotherapy with antifungal medicationOff-line breath analysis-
pharmacotherapy with antifungal medicationBlood analysis-
pharmacotherapy with anesthesia (including sedating, analgesReal-time SESI-MS breath analysis-
pharmacotherapy with antiepileptic medicationOff-line breath analysis-
pharmacotherapy with immuno suppressants and immune-modulatiOff-line breath analysis-
pharmacotherapy with antiepileptic medicationBlood analysis-
pharmacotherapy with immuno suppressants and immune-modulatiReal-time SESI-MS breath analysis-
pharmacotherapy with immuno suppressants and immune-modulatiBlood analysis-
pharmacotherapy with anesthesia (including sedating, analgesOff-line breath analysis-
pharmacotherapy with anesthesia (including sedating, analgesBlood analysis-
Primary Outcome Measures
NameTimeMethod
Days of hospitalizationapprox 30 days (from beginn hospitalisation to discharge date)

In the presentation of an acute disease the primary outcome will be days of hospitalization and its association with the exhaled breath pattern.

Change in Mass spectrometric profile of exhaled breath patternsWeek 0 (first regular clinic visit) to Follow-up visits (approx. years 1-10)

In the chronic presentation of the diseases, the mass spectrometric profile of exhaled breath patterns is analyzed

Change in Concentration of exhaled metabolites of pharmacotherapyWeek 0 (first regular clinic visit) to Follow-up visits (approx. years 1-10)

Concentration of exhaled metabolites of pharmacotherapy (breath metabolomics data)

Secondary Outcome Measures
NameTimeMethod
Correlations of identified molecules (acetone, glucose) in exhaled breath with body fluids (blood, saliva, urine) for T1D acute disease (mmol/l)0h, 2h, 4h, 6h, 8h, 12h, 18h, 24h, 36h, 48h, 72h (h =hours after hospital admission)

Correlations of identified molecules (acetone, glucose) in exhaled breath with body fluids (blood, saliva, urine) for T1D acute disease (mmol/l)

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 metabolitesapprox 10 years (from begin hospitalisation to discharge date and from first regular clinic visit to Follow-up visits)

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

Identification of chemical structure of exhaled molecules (acetone, glucose)approx 30 days (from begin hospitalisation to discharge date)

Identification of chemical structure of exhaled molecules (acetone, glucose)

Change in clinical endpoint (body temperature, Celsius) for correlation between clinical endpoint and the abundance of exhaled metabolitesapprox 10 years (from begin hospitalisation to discharge date and from first regular clinic visit to Follow-up visits)

Change in clinical endpoint (body temperature) for correlation between clinical endpoint and the abundance of exhaled metabolites

Change in clinical endpoint (blood pressure, mmHg) for correlation between clinical endpoint and the abundance of exhaled metabolitesapprox 10 years (from begin hospitalisation to discharge date and from first regular clinic visit to Follow-up visits)

Change in clinical endpoint (blood pressure) for correlation between clinical endpoint and the abundance of exhaled metabolites

Trial Locations

Locations (1)

University Children's Hospital Basel (UKBB)

🇨🇭

Basel, Switzerland

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