The HEADWIND Study - Part 3

Non-randomised, Controlled, Interventional Single-centre Study for the Design and Evaluation of an in Vehicle Hypoglycaemia Warning System in Diabetes - The HEADWIND Study Part 3

To analyse driving behavior of individuals with type 1 diabetes in eu- and mild hypoglycaemia using a validated research driving simulator. Based on the driving variables provided by the simulator the investigators aim at establishing algorithms capable of discriminating eu- and hypoglycemic driving patterns using machine learning classifiers.

Study Overview

• Status: Completed
• Conditions: Diabetes; Diabetes Mellitus, Type 1
• Intervention / Treatment: Other: Controlled hypoglycaemic state while driving with a driving simulator

Detailed Description

Hypoglycaemia is among the most relevant acute complications of diabetes mellitus. During hypoglycaemia physical, psychomotor, executive and cognitive function significantly deteriorate. These are important prerequisites for safe driving. Accordingly, hypoglycaemia has consistently been shown to be associated with an increased risk of driving accidents and is, therefore, regarded as one of the relevant factors in traffic safety. Therefore, this study aims at evaluating a machine-learning based approach using in-vehicle data to detect hypoglycemia during driving at an early stage.

During controlled eu- and hypoglycemia, participants with type 1 diabetes mellitus drive in a validated driving simulator while in-vehicle data are recorded. Based on this data, the investigators aim at building machine learning classifiers to detect hypoglycemia during driving.

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Switzerland
  • Bern, Switzerland
    • University Department of Endocrinology, Diabetology, Clinical Nutrition and Metabolism

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Informed Consent as documented by signature
• Type 1 Diabetes mellitus as defined by WHO for at least 1 year or is confirmed C-peptide negative (<100pmol/l with concomitant blood glucose >4 mmol/l)
• Subjects aged between 21-60 years
• HbA1c ≤ 9.0 % based on analysis from central laboratory
• Functional insulin treatment with insulin pump therapy or basis-bolus insulin for at least 3 months with good knowledge of insulin self-management
• Passed driver's examination at least 3 years before study inclusion. Possession of a valid Swiss driver's license.
• Active driving in the last 6 months before the study.

Exclusion Criteria:

• Contraindications to the drug used to induce hypoglycaemia (insulin aspart), known hypersensitivity or allergy to the adhesive patch used to attach the glucose sensor
• Women who are pregnant or breastfeeding
• Intention to become pregnant during the study
• Lack of safe contraception, defined as: Female participants of childbearing potential, not using and not willing to continue using a medically reliable method of contraception for the entire study duration, such as oral, injectable, or implantable contraceptives, or intrauterine contraceptive devices, or who are not using any other method considered sufficiently reliable by the investigator in individual cases.
• Other clinically significant concomitant disease states as judged by the investigator (e.g., renal failure, hepatic dysfunction, cardiovascular disease, etc.)
• Known or suspected non-compliance, drug or alcohol abuse
• Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc. of the participant
• Participation in another study with an investigational drug within the 30 days preceding and during the present study
• Previous enrolment into the current study
• Enrolment of the investigator, his/her family members, employees and other dependent persons
• Total daily insulin dose >2 IU/kg/day.
• Specific concomitant therapy washout requirements prior to and/or during study participation
• Physical or psychological disease is likely to interfere with the normal conduct of the study and interpretation of the study results as judged by the investigator (especially coronary heart disease or epilepsy).
• Current treatment with drugs known to interfere with metabolism (e.g. systemic corticosteroids, etc.) or driving performance (e.g. opioids, benzodiazepines)
• Patients not capable of driving with the driving simulator or patients experiencing motion sickness during the simulator test driving session.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Intervention group

Other: Controlled hypoglycaemic state while driving with a driving simulator; Participants arrive in the morning after an overnight fast. During the controlled hypoglycaemic state, participants drive on a designated circuit using a driving simulator. Initially, a euglycaemic state (5.0-8.0 mmol/L) is kept stable and blood glucose is then progressively declined targeting at a level between 3.0-3.5 mmol/L by administering insulin. Blood glucose is kept stable in the hypoglycaemic range for 30 minutes. Thereafter, blood glucose is raised again and kept stable for another 30 minutes at an euglycaemic level between 5.0-8.0mmol/L. During the procedure, the investigators analyse counterregulatory hormones. Heart rate, skin conductance, CGM values, eye movement and facial expression are recorded by a smart-watch, a CGM device, an eye-tracker and an onboard camera, respectively. Participants are blinded to the blood glucose values during the procedure and have to rate their symptoms and their driving performance on a 0-6 scale every 15 minutes.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diagnostic accuracy of the hypoglycemia warning system using in-vehicle data to detect hypoglycemia (blood glucose <3.9mmol/L) quantified as the area under the receiver operator characteristics curve (AUC ROC).	The machine learning model is developed and evaluated based on in-vehicle data generated in eu- and hypoglycemia. Detection performance of hypoglycemia is quantified as AUROC.	240 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diagnostic accuracy of the hypoglycemia warning system using wearable data to detect hypoglycemia (blood glucose <3.9mmol/L) quantified as the area under the receiver operator characteristics curve (AUC ROC).	The machine learning model is developed and evaluated based on wearable data recorded in eu- and hypoglycemia. Detection performance of hypoglycemia is quantified as AUROC.	240 minutes
Diagnostic accuracy of the hypoglycemia warning system using in-vehicle data and recordings of the continous glucose monitoring (CGM) system to detect hypoglycemia (blood glucose <3.9mmol/L) quantified as sensitivity and specificity.	The CGM device is in use during controlled eu- and hypoglycemia. Detection performance of hypoglycemia is quantified as sensitivity and specificity.	240 minutes
Diagnostic accuracy of the hypoglycemia warning system using wearable data and recordings of the CGM system to detect hypoglycemia (blood glucose <3.9mmol/L) quantified as sensitivity and specificity.	The CGM device is in use during controlled eu- and hypoglycemia. Detection performance of hypoglycemia is quantified as sensitivity and specificity.	240 minutes
Change in driving features over the glycemic trajectory.	Driving signals are recorded using a driving simulator.	240 minutes
Change of gaze coordinates over the glycemic trajectory.	Gaze coordinates are recorded using an eye-tracker device.	240 minutes
Change of head pose over the glycemic trajectory.	Head pose (position/rotation) are recorded using an eye-tracker device.	240 minutes
Change of heart rate over the glycemic trajectory	Heart rate is recorded using a holter-ECG device and wearables.	240 minutes
Change of heart rate variability over the glycemic trajectory	Heart rate variability is recorded using a holter-ECG device and wearables.	240 minutes
Change of electrodermal activity over the glycemic trajectory	Electrodermal activity is recorded using wearables.	240 minutes
Hypoglycemic symptoms over the glycemic trajectory.	Hypoglycemic symptoms are rated using a validated questionnaire (minimum score = 0, maximum score = 48, a higher score means more symptoms)	240 minutes
Time course of the hormonal response over the glycemic trajectory	Epinephrine, norepinephrine, glucagon, cortisol and growth hormone are measured at pre-defined time points.	Time Frame: 240 minutes
Self assessment of driving performance over the glycemic trajectory.	Participants rate their driving performance on a 7-point Lickert Scale (lower value means poorer driving performance).	240 minutes
CGM accuracy over the glycemic trajectory	CGM values will be recorded using a CGM sensor (Dexcom G6). Venous blood glucose is considered as the reference. Accuracy will be quantified using mean absolute relative difference (MARD) from the gold-standard and using the Clarke error grid.	240 minutes
Incidence of Adverse Events (AEs)	Adverse Events will be recorded at each study visit.	2 weeks, from screening to close out visit in each participant
Incidence of Serious Adverse Events (SAEs)	Serious Adverse Events will be recorded at each study visit.	2 weeks, from screening to close out visit in each participant
Emotional response to hypoglycemia warning system	Physiological response is measured using an electro-dermal activity sensor (skin conductance) and eye tracker (eye blinks). Self-reported emotional response is assessed with scales (e.g., valence, arousal, annoyance, sense of urgency).	240 minutes
Technology acceptance of the hypoglycemia warning system	Technology acceptance is measured with user experience questionnaires, such as the Unified Technology Acceptance and Use of Technology Questionnaire from Venkatesh et al. (2012) and free words associations.	240 minutes

Collaborators and Investigators

• Sponsor: University Hospital Inselspital, Berne
• Collaborators: ETH Zurich; University of St.Gallen
• Investigators: Principal Investigator: Christoph Stettler, MD, Inselspital, Bern University Hospital, Universität of Bern

Study record dates

Study Major Dates

• Study Start (Actual): November 29, 2021
• Primary Completion (Actual): March 3, 2022
• Study Completion (Actual): March 3, 2022

Study Registration Dates

• First Submitted: December 20, 2021
• First Submitted That Met QC Criteria: December 20, 2021
• First Posted (Actual): January 10, 2022

Study Record Updates

• Last Update Posted (Actual): May 5, 2022
• Last Update Submitted That Met QC Criteria: May 4, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: Hypoglycemia; Driving; Automotive Technology; Hypoglycaemia; Driving simulator
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Hypoglycemia; Physiological Effects of Drugs; Hypoglycemic Agents
• Other Study ID Numbers: HEADWIND 3

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Any requests for raw data will be reviewed by the HEADWIND scientific study board comprising the principal investigator (PI) and Co-PI as well as senior researchers leading the involved research groups at Inselspital Bern, ETH Zurich, and University of St. Gallen. Only applications for non-commercial use will be considered and should be sent to the PI (Prof. Ch. Stettler). Applications should outline the purpose for the raw-data transfer. Any data that can be shared will need approval from the HEADWIND scientific study board and a Material Transfer Agreement in place. All data shared will be de-identified.
• IPD Sharing Access Criteria: Only applications for non-commercial use will be considered and should be sent to the PI (Prof. Ch. Stettler).
• IPD Sharing Supporting Information Type: Study Protocol; Analytic Code

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No