Diabetes Mellitus, Type 1
Conditions
Keywords
Hypoglycaemia
Brief summary
To evaluate the technical performance of the hyposafe H02 during everyday activities and during insulin-induced hypoglycaemia, in addition to safety issues associated with the implantation and use of the hyposafe H02 in subjects with type 1 diabetes.
Detailed description
While a finger prick test accurately measures the blood glucose level, it does not provide continuous measurements and hence it is unreliable as a hypoglycaemia notification. Recent studies have indicated that the use of continuous glucose monitoring (CGM) reduces the risk of severe hypoglycaemia. However, some find these devices troublesome to use and are annoyed by the inaccuracy of the measurements and even after short-term use the coverage in subgroups of patients is as low as 50% of the time. Thus, there is a medical need for a reliable hypoglycaemia notification which is easy and convenient to use and with high sensitivity and high rate of positive prediction. This clinical investigation is designed to evaluate the sensitivity and the positive predictive value of the Hyposafe H02 in subjects with type 1 diabetes during everyday activities and during insulin-induced hypoglycaemia. In addition, the investigation provides information regarding safety and usability of the device. This to verify that the Hyposafe H02 works as intended in subjects with type 1 diabetes before proceeding with a larger study in subjects with type 1 diabetes.
Interventions
DEVICEhyposafe H02
hypoglycaemia notification device
Sponsors
UNEEG Medical A/S
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Informed consent obtained before any study related activities * Type 1 diabetes diagnosed at least five years prior to inclusion in the study * Impaired awareness and/or history of at least one severe hypoglycaemia within the preceding year
Exclusion criteria
* Severe cardiac disease * History of stroke or cerebral haemorrhage and any other structural cerebral disease * Active cancer or cancer diagnosis within the past 5 years * Uraemia defined as s-creatinine ≥ 3 times upper reference value * Liver disease defined as s-ALAT ≥ 3 times upper reference interval * Epilepsy * Use of antiepileptic drugs for any indication * Clinically important hearing impairment * Use of active implantable medical device including pacemaker and ICD-unit and cochlear implant * Use of following drugs: Chemotherapeutic drugs of any kind, Methotrexate, Third generation antipsychotic drugs (aripiprazole, quetiapine, clozapine, ziprasidone, paliperidone, risperidone, sertindole, amisulpride, olanzapine) * Contraindications to the local anaesthetic used during implantation * Known or suspected abuse of alcohol or any other neuro-active substances * Infection at the site of device implantation * Any haemorrhagic disease * Females of childbearing potential who are pregnant or intend to become pregnant or are not using adequate contraceptive methods throughout the study * Performing extreme sport, including scuba diving (snorkel diving is allowed) or parachute jumping * Incapable of understanding the subject information or unlikely to complete the study for any reason * Operating MRI scanners * Operating handheld transceivers for communication (e.g. within the police, medical, fire, air traffic control, marine or military) * Working at broadcast stations for television or FM/DAB radio * Use of CGM or FGM with visible glucose measurements and activated glucose notifications * Involved in therapies with medical devices that deliver electrical energy into the area around the implant
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Sensitivity | 3 months | Number of spontaneous hypoglycaemic episodes detected by the hyposafe H02 compared to the total number of validated spontaneous hypoglycaemic episodes. Validation was performed by self-measured blood glucose (SMBG). |
| Positive Predictive Value | 3 months | Number of validated spontaneous hypoglycaemic episodes detected by the hyposafe H02 compared to the total number of notification from the hyposafe H02. Validation was performed by self-measured blood glucose (SMBG). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Sensitivity During Insulin-induced Hypoglycaemia | 2 days | Number of insulin-induced hypoglycaemic episodes detected by the hyposafe H02 compared to the total number of insulin-induced hypoglycaemic episodes. |
| Positive Predictive Value for Insulin-induced Hypoglycaemia | 2 days | Number of insulin-induced hypoglycaemic episodes detected by the hyposafe H02 compared to the total number of alerts from the hyposafe H02 |
| Number of Participants With a Satisfactory EEG Quality Test | start up and after 3 months | The EEG quality test was performed twice in the study. At start up and at the end of the study. Evaluation was based on visual review of EEG of known phenomena and artefacts by an experienced EEG reviewer. |
| Change in Impedance (kOhm) Over Time | start up and after 3 months | The EEG performance was measured as the impedance as a function of time. An impedance value below 5 kOhm is considered very good. Number of participants with impedance values below 5 kOhm and no change over time is reported. |
| Device Deficiencies | 4 months | Total number of device deficiencies |
| Overall Sensitivity | 3 months | Total number of hypoglycaemic episodes detected by the hyposafe H02 compared to the total number of validated hypoglycaemic episodes. Validation was performed by self-measured blood glucose (SMBG) or plasma glucose (PG). |
| Development in Discomfort Over Time Based on Questionnaires | 3 weeks, 7 weeks and 15 weeks after implantation (baseline) | Implant discomfort over time were evaluated at 3 time points; on average 3 weeks, 7 weeks and 15 weeks after implantation (baseline). Here the categories were converted into cardinal numbers: ranging from strongly agree=5 to strongly disagree=1 on the statement ''The implant has not caused discomfort in the past two days'. |
| User Satisfaction Based on Questionnaire | 1 month | User satisfaction were evaluated as to whether the subjects wished to continue to use the device |
| Mean Number of Hours of Use Per Device | 3 months | Mean number of hours of use per device is measured as recording time of device |
| Response to Hypoglycaemia Notification | 3 months | Response to hypoglyceamia notifications measured as the participants were able to take preventive actions upon notification of hypoglycaemia in an outpatient settings (the spontaneous hypoglycemic episodes) and during insulin-induced hypoglycaemia |
| Alarm Fatigue Based on Questionnaire | 3 months | The participants were given a questionnaire regarding their preferences for sensitivity and false alarms at the end of the study. Reporting are for preferences during the day. |
| Mean Glucose Level at the Time of a Hypoglycaemia Notification | 3 months | Glucose levels were measured at the time of a hypoglycaemia notification during an outpatients settings (the spontaneous episodes) and during insulin-induced hypoglycaemia (the insulin-induced episodes) |
| Overall Positive Predictive Value | 3 months | Total number of validated hypoglycaemic episodes detected by the hyposafe H02 compared to the total number of alerts from the hyposafe H02. Validation was performed by self-measured blood glucose (SMBG) or plasma glucose (PG). |
Countries
Denmark
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Overall Study: Hyposafe H02 All subjects included are assigned to hyposafe H02-testing
hyposafe H02: hypoglycaemia notification device | 8 |
| Total | 8 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Overall Study: Hyposafe H02 |
|---|---|
| Age, Continuous | 57.5 years STANDARD_DEVIATION 8.1 |
| Dieabetes duration | 35 years STANDARD_DEVIATION 16.1 |
| Race/Ethnicity, Customized Caucasian | 8 Participants |
| Region of Enrollment Denmark | 8 participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 8 |
| other Total, other adverse events | 8 / 8 |
| serious Total, serious adverse events | 0 / 8 |
Outcome results
Primary
Positive Predictive Value
Number of validated spontaneous hypoglycaemic episodes detected by the hyposafe H02 compared to the total number of notification from the hyposafe H02. Validation was performed by self-measured blood glucose (SMBG).
Time frame: 3 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Overall Study: Hyposafe H02 | Positive Predictive Value | Positive predictive value (day) | 8 Percentage |
| Overall Study: Hyposafe H02 | Positive Predictive Value | Positive predictive value (night) | 2 Percentage |
Primary
Sensitivity
Number of spontaneous hypoglycaemic episodes detected by the hyposafe H02 compared to the total number of validated spontaneous hypoglycaemic episodes. Validation was performed by self-measured blood glucose (SMBG).
Time frame: 3 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Overall Study: Hyposafe H02 | Sensitivity | Sensitivity (day) | 100 Percentage |
| Overall Study: Hyposafe H02 | Sensitivity | Sensitivity (night) | 100 Percentage |
Secondary
Alarm Fatigue Based on Questionnaire
The participants were given a questionnaire regarding their preferences for sensitivity and false alarms at the end of the study. Reporting are for preferences during the day.
Time frame: 3 months
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Overall Study: Hyposafe H02 | Alarm Fatigue Based on Questionnaire | 95% sensitivity - 15 false notifications weekly | 2 Participants |
| Overall Study: Hyposafe H02 | Alarm Fatigue Based on Questionnaire | 90% sensitivity - 9 false notifications weekly | 3 Participants |
Secondary
Change in Impedance (kOhm) Over Time
The EEG performance was measured as the impedance as a function of time. An impedance value below 5 kOhm is considered very good. Number of participants with impedance values below 5 kOhm and no change over time is reported.
Time frame: start up and after 3 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Overall Study: Hyposafe H02 | Change in Impedance (kOhm) Over Time | 7 Participants |
Secondary
Development in Discomfort Over Time Based on Questionnaires
Implant discomfort over time were evaluated at 3 time points; on average 3 weeks, 7 weeks and 15 weeks after implantation (baseline). Here the categories were converted into cardinal numbers: ranging from strongly agree=5 to strongly disagree=1 on the statement ''The implant has not caused discomfort in the past two days'.
Time frame: 3 weeks, 7 weeks and 15 weeks after implantation (baseline)
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Overall Study: Hyposafe H02 | Development in Discomfort Over Time Based on Questionnaires | 3 weeks after implantation | 4.1 Score on a scale |
| Overall Study: Hyposafe H02 | Development in Discomfort Over Time Based on Questionnaires | 7 weeks after implantation | 4.7 Score on a scale |
| Overall Study: Hyposafe H02 | Development in Discomfort Over Time Based on Questionnaires | 15 weeks after implantation | 4.9 Score on a scale |
Secondary
Device Deficiencies
Total number of device deficiencies
Time frame: 4 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Overall Study: Hyposafe H02 | Device Deficiencies | 15 Counts |
Secondary
Mean Glucose Level at the Time of a Hypoglycaemia Notification
Glucose levels were measured at the time of a hypoglycaemia notification during an outpatients settings (the spontaneous episodes) and during insulin-induced hypoglycaemia (the insulin-induced episodes)
Time frame: 3 months
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Overall Study: Hyposafe H02 | Mean Glucose Level at the Time of a Hypoglycaemia Notification | Spontanous episodes | 2.4 mmol/L glucose |
| Overall Study: Hyposafe H02 | Mean Glucose Level at the Time of a Hypoglycaemia Notification | Insulin-induced episodes | 2 mmol/L glucose |
Secondary
Mean Number of Hours of Use Per Device
Mean number of hours of use per device is measured as recording time of device
Time frame: 3 months
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Overall Study: Hyposafe H02 | Mean Number of Hours of Use Per Device | Use per day | 13.5 Hours |
| Overall Study: Hyposafe H02 | Mean Number of Hours of Use Per Device | Use per night | 8.2 Hours |
Secondary
Number of Participants With a Satisfactory EEG Quality Test
The EEG quality test was performed twice in the study. At start up and at the end of the study. Evaluation was based on visual review of EEG of known phenomena and artefacts by an experienced EEG reviewer.
Time frame: start up and after 3 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Overall Study: Hyposafe H02 | Number of Participants With a Satisfactory EEG Quality Test | 7 Participants |
Secondary
Overall Positive Predictive Value
Total number of validated hypoglycaemic episodes detected by the hyposafe H02 compared to the total number of alerts from the hyposafe H02. Validation was performed by self-measured blood glucose (SMBG) or plasma glucose (PG).
Time frame: 3 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Overall Study: Hyposafe H02 | Overall Positive Predictive Value | 11 Percentage |
Secondary
Overall Sensitivity
Total number of hypoglycaemic episodes detected by the hyposafe H02 compared to the total number of validated hypoglycaemic episodes. Validation was performed by self-measured blood glucose (SMBG) or plasma glucose (PG).
Time frame: 3 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Overall Study: Hyposafe H02 | Overall Sensitivity | 81 Percentage |
Secondary
Positive Predictive Value for Insulin-induced Hypoglycaemia
Number of insulin-induced hypoglycaemic episodes detected by the hyposafe H02 compared to the total number of alerts from the hyposafe H02
Time frame: 2 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Overall Study: Hyposafe H02 | Positive Predictive Value for Insulin-induced Hypoglycaemia | 100 Percentage |
Secondary
Response to Hypoglycaemia Notification
Response to hypoglyceamia notifications measured as the participants were able to take preventive actions upon notification of hypoglycaemia in an outpatient settings (the spontaneous hypoglycemic episodes) and during insulin-induced hypoglycaemia
Time frame: 3 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Overall Study: Hyposafe H02 | Response to Hypoglycaemia Notification | Spontaneous hypoglycemic episodes | 100 Percentage |
| Overall Study: Hyposafe H02 | Response to Hypoglycaemia Notification | Insulin-induced hypoglycemic episodes | 87.5 Percentage |
Secondary
Sensitivity During Insulin-induced Hypoglycaemia
Number of insulin-induced hypoglycaemic episodes detected by the hyposafe H02 compared to the total number of insulin-induced hypoglycaemic episodes.
Time frame: 2 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Overall Study: Hyposafe H02 | Sensitivity During Insulin-induced Hypoglycaemia | 57 Percentage |
Secondary
User Satisfaction Based on Questionnaire
User satisfaction were evaluated as to whether the subjects wished to continue to use the device
Time frame: 1 month
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Overall Study: Hyposafe H02 | User Satisfaction Based on Questionnaire | Number of participants that would like to continue to use the device | 2 Participants |
| Overall Study: Hyposafe H02 | User Satisfaction Based on Questionnaire | Number of participants that would not like to continue to use the device | 5 Participants |