Acceleration of Insulin Action by Hyaluronidase During Closed-Loop Therapy
Condition: Type 1 Diabetes
MeSH terms: Diabetes Mellitus, Type 1
Study type: Interventional
Phase: Early Phase 1

Summary: 
      "Closed loop artificial pancreas" systems have been under development for the control of
      blood sugars in those living with diabetes. These systems consist of a continuous glucose
      sensor, which sends a signal to a computer program that automatically determines how much
      insulin to give. The computer program then tells an insulin pump to deliver the insulin.
      While such systems have been tested under a number of conditions, post-meal blood sugars are
      difficult to control. Specifically, we will be looking to see if using hyaluronidase improves
      the ability of the closed loop artificial pancreas to better respond to meal related highs
      and lows.
    

Detailed description: 
      To investigate the effect of rHuPH20, an adjuvant that accelerates the dispersion and
      absorption of subcutaneously injected or infused drugs, on mitigating post-prandial blood
      glucose excursions when injected separately or co-formulated with insulin during closed-loop
      therapy for youth and young adults with type 1 diabetes. Closed-loop control will be achieved
      using external subcutaneous real-time continuous glucose monitoring and continuous
      subcutaneous insulin infusion along with a computerized algorithm to link these two
      processes.

      Specific Aim 1: To examine whether co-formulation rHuPH20 with analog insulin (INS-PH20)or,
      alternately, pre-administration of rHuPH20 (PH20-preRx) at the time of infusion set placement
      prior to initiation of closed-loop (CL) insulin delivery will reduce peak-postprandial
      glucose concentrations and total glucose area under the curve of the meal excursions in short
      term inpatient experiments.

      Specific Aim 2: To investigate whether accelerated insulin absorption by rHuPH20, delivered
      as described above, will also result in a reduction of late-post-prandial hyperinsulinemia
      and late post-prandial hypoglycemia during CL insulin delivery.

      Specific Aim 3: To compare the insulin accelerator effect of INS-PH20 to that of PH20-preRx,
      based on post prandial glucose excursions during closed-loop therapy

      We hypothesize that; utilization of PH20 either as a separate injection (PH20-preRx) or in a
      co-formulation with insulin (INS-PH20) during CL therapy will reduce peak-postprandial
      glucose concentrations and total glucose under the curve of the meal excursion as compared to
      CL control without any intervention, and we propose that the use of PH20-preRx and INS-PH20
      will be well tolerated when delivered in youth and young adults in a closed-loop setting.
    

Intervention name(s): ePID closed loop system; hyaluronidase; Lispro-PH20
Intervention type(s): Device; Drug; Drug
Intervention description(s): Insulin pump controlled by closed loop unit and algorithm
Other intervention name(s): rHuPH20; insulin-hyaluronidase co-formulation
Intervention MeSH terms: Insulin
Allocation: Non-Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: diabetes, insulin,post prandial, closed loop, artificial pancreas, hyperglycemia