Phase 2 Study of Adaptive Insulin Meal Supervisor (AIMS) in Adults With Type 1 Diabetes Mellitus
Condition: Diabetes Mellitus, Type 1
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1
Study type: Interventional

Summary: 
      In this study, a closed-loop Adaptive Insulin Meal Supervisor system (AIMS) utilizing
      continuous glucose monitoring (CGM), a subcutaneous insulin pump and standard pramlintide
      therapy will be applied in individuals with type 1 diabetes. Pramlintide, a drug well
      recognized to help control hyperglycemia with meals, will be evaluated in both closed loop
      and open loop control. It is expected that the closed loop control condition with pramlintide
      will improve glycemia, thus combining better control with enhanced safety. In a recent pilot
      study, the investigators started testing this concept and collected data showing that in
      order to be successful such strategy must have a controller equipped with the ability to
      optimize the configuration and timing of meal boluses with concomitant administration of
      pramlintide. Our preliminary data and review of previously unavailable individual data from a
      German study indicate a large individual variability in the timing of the appearance of meal
      insulin needs. Thus, for both adequate safety and efficacy of meal insulin on pramlintide,
      the investigators have developed a new closed-loop controller that accounts for the
      variability in the individual responses to a meal and meal delays, the Adaptive Insulin Meal
      Supervisor system (AIMS). In this study, the performance of a combination between the AIMS
      system and a standard pramlintide treatment will be tested versus the standard pramlintide
      treatment alone.
    

Detailed description: 
      The current study will probe the concept that if a Model Predictive Control insulin delivery
      strategy for closed-loop glucose control supervised by a safety system is coupled with a
      standard amylin replacement therapy in patients with type 1 diabetes the resulting combined
      treatment will unify the benefits of both individual therapies. In order to reduce post-meal
      blood glucose excursions in patients with type 1 diabetes mellitus, pramlintide (an analog of
      the human β-cell hormone, amylin) has been utilized, thus dealing with the problem or meal
      hyperglycemia more effectively than insulin infusion alone. Pramlintide has been successful
      in maintaining more normal blood glucose concentrations by significantly improving the
      postprandial glucose excursions in these patients when added to their mealtime insulin to
      mimic more closely the diurnal β-cell secretory pattern seen in normal physiology. However,
      pramlintide treatment can result in post-prandial hypoglycemia primarily due to overbolusing
      with insulin. Closed-loop systems have shown potential for significantly reducing
      hypoglycemia. A combined closed-loop insulin + pramlintide therapy could provide advantages
      over each of the individual therapies, and may also provide certain benefits with respect to
      weight control and improvement in sense of well being while decreasing glucose variability. A
      potentially important secondary benefit of combining the pramlintide treatment with a precise
      insulin delivery by the closed-loop system is that, based upon animal studies performed by
      the research team, a moderate inhibition of glucagon, as is usually achieved with pramlintide
      treatment, is anticipated to potentially improve the safety of insulin treatment as well by
      enhancing the glucagon response to hypoglycemia, which are usually impaired in type 1
      diabetes, if it should occur in the early postprandial period.
    

Intervention name(s): Closed Loop with Pramlintide
Intervention type(s): Device
Intervention description(s): A closed-loop automated insulin management system (Adaptive Insulin Meal Supervisor- AIMS) for meals utilizing continuous glucose monitoring (CGM)and subcutaneous insulin pump and a standard pramlintide therapy will be compared to a standard pramlintide therapy alone to control glucose levels in individuals with type 1 diabetes. DiAs is controlled by the subject, with assistance from the study personnel as needed.
Intervention MeSH terms: Pramlintide
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Pramlintide; Closed Loop; Continuous Glucose Monitor (CGM); Diabetes Assistant (DiAs)