First-in-human Testing of a Multi-Analyte Sensor Platform for Glucose/Lactate/Oxygen/Choline in People with Diabetes

This study is a single site feasibility study to collect data on the glucose/lactate and lactate/choline/oxygen sensor performance of a multianalyte sensor platform. There will be no randomisation of participants. The data will not be blinded to the investigators. Data from study devices will not impact upon decisions involving care of the participants as sensor generated glucose or other analyte data will not be available to the participants. All participants will wear the investigational sensing platform for the approximate 3-4 day duration. Each participant will wear the following: • Two separate multi-analyte sensors (glucose/lactate and lactate/choline/oxygen) inserted subcutaneously preferably in the upper arm area and connected to a data recorder. • A commercially available continuous glucose monitor inserted in the upper arms of the participant. If the participant is managed with multiple daily injections, they will continue to administer rapid acting and intermediate/ basal insulin as per established regimens. If the participant is managed using an insulin pump they will continue to infuse subcutaneous rapid acting insulin as per the participant’s established insulin pump infusion protocols. Participation in this research study will occur over approximately 3-4 days and participants will be required to attend the clinical trials centre at St Vincent’s Hospital, Melbourne twice, on day 1 and day 4. On the first study day, participants will attend the trials centre at ~7:30AM having fasted overnight (unless required to treat a hypoglycemic event). The first study visit will run for approximately 7 hours. Informed consent will be obtained from all participants. If a participant meets all screening eligibility criteria, he or she will be considered enrolled into the study. Participant demographic and baseline characteristics, including age, gender, race, ethnicity, and medical diagnosis will be collected during this visit. A trained study investigator will insert the investigational and study sensors. The insertion of the investigational sensors is comparable to commercially available interstitial sensors. Immediately after sensor insertion and warm-up, a meal test followed by a high-intensity exercise challenge will occur, resulting in acute increases in glucose and lactate respectively. Blood glucose levels are to be between 4.0-15.0 mmol/L and blood ketones are to be <0.6 mmol/L prior to commencing the test meal protocol. A standardised test meal containing 65g carbohydrate will be consumed by each participant immediately following sensor insertion and sensor warm-up. Participants will administer their usual insulin dose using either an injection or an insulin pump immediately prior to the meal. Venous blood glucose (study meter and YSI) and lactate (YSI) levels will be measured immediately following sensor insertion (baseline) and every 15min following the test-meal for four hours. Four hours following the meal test, participants will undergo 40min of high-intensity exercise. This will involve 40 minutes of exercise on the cycle ergometer, including 5x4min ‘hard’ intervals, interspersed with 4min rest. The 4min ‘hard’ intervals will be performed at an intensity that elicits approximately 80-90% of the participants’ age-predicted heart rate maximum, and a perceived rating of exertion (RPE) of 8-10, on a 10-point scale. This protocol has been previously demonstrated by our group to produce a significant lactate excursion in people with type 1 diabetes. During exercise venous blood samples for glucose and lactate will be collected at 5-minute intervals and then at 10-minute intervals until the end of the study visit, which will occur 60min after exercise completion. Following the initial visit, participants will continue wearing the sensors at home on Days 2 and 3. Participants will be instructed to monitor glucose levels at home a minimum of 8 times a day (pre-meals and 2 hours post-meals) between visits. Glucose readings will be recorded along with the amount and timing of insulin injected and a log of exercise/physical activity in a diary. Any exercise for 10 minutes duration or longer will be recorded, along with the type and intensity of the exercise performed. Fingerprick blood lactate readings will also occur at least 3 times per day, at any time (for ease, measurements can be taken at the same time as glucose). Additionally, fingerprick blood lactate readings should occur after any exercise performed in the study window. The second study visit will occur on Day 4 of the study. The second visit will involve the same protocol as in visit 1 (without sensor insertion), repeating the Meal Test and Exercise Test. This study visit will last for approximately 6-7 hours. Participants will have the investigational and study devices removed following the testing procedures and will exit the study.