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

Type 1 Diabetes Clinical Trial

— EBECA  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04461821
• Other study ID #: 2020-00778; ks20Sinues
• Status: Recruiting
• Start date: September 11, 2020
• Est. completion date: July 2030

Study information

• Verified date: February 2024
• Source: University Children's Hospital Basel
• Contact: Pablo Sinues, Prof. Dr.
• Phone: +41 61 704 2949
• Email: pablo.sinues[@]ukbb.ch
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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

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 information / eligibility

• Status: Recruiting
• Enrollment: 3600
• Est. completion date: July 2030
• Est. primary completion date: July 2030
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 22 Years

Eligibility

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.

Related Conditions & MeSH terms

• Nervous System Diseases
• Neurological Disorders
• Respiration Disorders
• Respiratory Diseases
• Respiratory Tract Diseases
• Type 1 Diabetes

Intervention

Diagnostic Test:
• Real-time SESI-MS breath analysis
Participants will be asked to refrain from eating, drinking, chewing gum use or brushing their teeth at least 1 hour before the measurements will be performed. Room temperature and lighting will be set at the same level for all measurements. Participants will exhale through a disposable mouthpiece into a commercially available SESI source (FIT S.L., Spain). While performing full exhalations, the subjects will keep the pressure through the sampling line at a fixed value monitored by a digital manometer. Breath prints will be collected in real-time recording multiple replicates (typically six in positive and negative ion mode). The whole procedure is absolutely non-invasive and is usually accomplished without any effort in around 15 min per subject.
• Off-line breath analysis
In young children below the age of 4 not capable of completing the on-line exhalation maneuvers, or in cases when the patient needs cannot approach the mass spectrometer, the sample will be collected off-line. They will be asked to exhale into a bag that will be transported to the lab and deflated into the mass spectrometer for analysis. Exhaled breath of patients under anesthesia will also collected using available ventilation system in the operation theatre.
• Blood analysis
Blood analysis done in patients who undergo regular blood sampling needed for clinical routine laboratory controls. This includes i) children and adolescents receiving medications which require TDM ii) patients with acute diseases such as TD1 and pneumonia and iii) patients with chronic diseases such as asthma bronchiale. For those patients where a blood sample is drawn during the clinical routine, an additional blood sample consisting of only several blood drops will be collected using the same blood sampling line. No additional venous puncture for research purpose will be done.
• Saliva analysis
During the diagnostic and therapeutic work-up of T1D patients, saliva samples are collected during the clinical routine. For those patients, additional samples will be obtained by clinically trained investigators.
• Urine analysis
During the diagnostic and therapeutic work-up of T1D patients, urine samples are collected during the clinical routine. For those patients, additional samples will be obtained by clinically trained investigators.

Locations

Country	Name	City	State
Switzerland	University Children's Hospital Basel (UKBB)	Basel

Sponsors (3)

Lead Sponsor	Collaborator
University Children's Hospital Basel	Fondation Botnar (Switzerland), Swiss National Science Foundation

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Days of hospitalization	In the presentation of an acute disease the primary outcome will be days of hospitalization and its association with the exhaled breath pattern.	approx 30 days (from beginn hospitalisation to discharge date)
Primary	Change in Mass spectrometric profile of exhaled breath patterns	In the chronic presentation of the diseases, the mass spectrometric profile of exhaled breath patterns is analyzed	Week 0 (first regular clinic visit) to Follow-up visits (approx. years 1-10)
Primary	Change in Concentration of exhaled metabolites of pharmacotherapy	Concentration of exhaled metabolites of pharmacotherapy (breath metabolomics data)	Week 0 (first regular clinic visit) to Follow-up visits (approx. years 1-10)
Secondary	Identification of chemical structure of exhaled molecules (acetone, glucose)	Identification of chemical structure of exhaled molecules (acetone, glucose)	approx 30 days (from begin hospitalisation to discharge date)
Secondary	Correlations of identified molecules (acetone, glucose) in exhaled breath with body fluids (blood, saliva, urine) for T1D acute disease (mmol/l)	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)
Secondary	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	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	approx 10 years (from begin hospitalisation to discharge date and from first regular clinic visit to Follow-up visits)
Secondary	Change in clinical endpoint (body temperature, Celsius) for correlation between clinical endpoint and the abundance of exhaled metabolites	Change in clinical endpoint (body temperature) for correlation between clinical endpoint and the abundance of exhaled metabolites	approx 10 years (from begin hospitalisation to discharge date and from first regular clinic visit to Follow-up visits)
Secondary	Change in clinical endpoint (blood pressure, mmHg) for correlation between clinical endpoint and the abundance of exhaled metabolites	Change in clinical endpoint (blood pressure) for correlation between clinical endpoint and the abundance of exhaled metabolites	approx 10 years (from begin hospitalisation to discharge date and from first regular clinic visit to Follow-up visits)