Safety and Feasibility of an Insulin Sensitivity-Informed Bolus Calculator in Type 1 Diabetes
Condition: Type 1 Diabetes Mellitus
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1; Insulin Resistance; Hypersensitivity
Study type: Interventional

Summary: 
      This is a single-center randomized crossover trial. The investigators will target completion
      of 15 adults (age 18-65 years) with Type 1 Diabetes who use an insulin pump. After completion
      of the Screening Visit, each subject will participate in a 28-day at home Data Collection
      Period while using their personal insulin pump, a personal glucometer, a study CGM, and a
      study activity tracker (i.e., Fitbit). This data collection period may be extended to obtain
      to gather more days of quality data, if needed per principal investigator judgement.

      Once the data has been collected and processed, subjects will participate in two 24-hour
      admissions (Experimental and Control Admission) in a semi-controlled environment (i.e.,
      hotel), performed in the assigned random order. During both admissions, subjects will use the
      personal insulin pump and glucometer, and a study CGM. The exercise session will consist of
      three 15-minute bouts of moderate-intensity exercise (i.e., stationary bicycle). Subjects
      will be provided a controlled dinner; the SI-informed bolus calculator will be used in the
      Experimental Admission while standard therapy will be used in the Control Admission. Subjects
      will then be observed overnight and discharged in the following morning.
    

Detailed description: 
      Individuals with Type 1 Diabetes (T1D) require exogenous insulin to keep their blood glucose
      concentration in a safe euglycemic range, because of the absent internal insulin secretion
      caused by the autoimmune destruction of pancreatic beta-cells. As a consequence, the quality
      of glycemic control in T1D is heavily dependent on multiple daily treatment decisions by the
      patients, which are complicated by a wide variety of factors influencing insulin demand
      (e.g., circadian rhythms, physical activity, food, stress, etc.). Insulin sensitivity (SI) is
      a key metabolic parameter in diabetes as it informs on how sensitive the body is to the
      effects of insulin. In general, if someone has higher SI, the amount of insulin required to
      lower his blood glucose levels is smaller than that needed by someone who has low
      sensitivity. However, SI levels within the same person are not constant, and fluctuations of
      SI happen very frequently in the life of subjects with diabetes, making insulin dosing very
      difficult to tune.

      In this context, the aim of this research project is to develop an SI-informed insulin bolus
      calculator, with the aim of tailoring the insulin dose to the individual's insulin need at
      the time the bolus is administered. The SI-informed bolus calculator relies on a Kalman
      filter-based algorithm which uses continuous glucose monitoring (CGM) data, insulin, and meal
      records to estimate SI. For each subject, a 24-hour SI profile is computed using data
      collected over several days of monitoring, and the optimal bolus is then computed by
      adjusting the standard insulin dose by the ratio between usual SI (from the profile) and
      real-time SI of the individual at the time the bolus is administered. In this way, if the
      real-time SI is larger/smaller than the profile SI at that time of day, the insulin dose will
      be reduced/incremented accordingly.

      The study is thus designed as a single-center randomized clinical trial targeting completion
      of 15 subjects, who will undergo a 28-day at home Data Collection Period followed by two
      24-hour admissions (Control and Experimental Admission) performed in random order in a
      semi-controlled environment (i.e., hotel). The Data Collection is meant to collect data
      needed to build the 24-hour SI profile for the subject. During the admissions, subjects will
      undergo a 45-minute afternoon exercise session designed to alter the late-afternoon/evening
      SI. The dinner meal will then be controlled, and the postprandial glycemic control obtained
      using the standard bolus calculator (Control Admission) will be compared to the control
      obtained in response to the optimized SI-informed bolus calculator (Experimental Admission).
      Metrics computed on CGM data will be compared between the two admissions, including mean
      blood glucose, time above 250 and 300 mg/dL, time below 70 and 54 mg/dL, and time in 70-180
      mg/dL, the primary outcome being the postprandial exposure to hypoglycemia as measured by the
      Low Blood Glucose Index (a glycemic variability indicator which summarizes the number and
      extent of low blood glucose events in one single number). If successful, this study will
      provide a novel, data-oriented paradigm for insulin dosing in T1D.
    

Intervention name(s): SI-Informed Bolus Calculator
Intervention type(s): Other
Intervention description(s): The SI-Informed Bolus Calculator will be used to dose the dinner meal insulin bolus during the Experimental Admission
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Other
Keywords: Continuous Glucose Monitor; Insulin Sensitivity; Exercise