Study on the Effects on Blood Glucose Following Intradermal and Subcutaneous Dosing of Insulin in Diabetic Patients
Condition: Diabetes
MeSH terms: Diabetes Mellitus
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      The purpose of this study is to compare the effects of bolus delivery of insulin when
      delivered either intradermally (in the skin) or subcutaneously (under the skin) in diabetics.
    

Detailed description: 
      Each patient will participate in 10 visits of which the first, Visit 1, is a Screening Visit.

      Visit 2 will consist of a brief isoglycemic clamp with a single IV insulin challenge to
      determine insulin sensitivity. A subsequent test meal and single SC insulin dose (off clamp)
      will be done to determine the nominal coverage dose of insulin for a mixed meal containing
      60g of carbohydrate. This nominal dose will form the basis of insulin bolus dosing for the
      remainder of the study visits.

      For Visits 3-9, patients will come to the institute in the early morning 24 hours prior to
      the meal test for the application of a Continuous Glucose Monitor (Dexcom Seven Plus™,
      Dexcom, INC). Subjects will receive standardized meals during the day and their blood glucose
      will be stabilized overnight to a concentration of 115±15 mg/dL via IV insulin and/or glucose
      infusions. The next morning the subjects will start the experimental intervention.
      Immediately prior to standardized meals (2 minutes before eating) the patients will receive
      insulin by either the ID or SC route, followed by the breakfast (rapidly absorbed carb) meal
      at time point T0. Meal consumption will occur over a 10 to 15 min time interval. Blood
      glucose excursions will be observed in the 6 hours thereafter (until T= 360 min). Between
      hours 6 to 7, BG may be re-stabilized to starting values (115±15 mg/dL) by administration of
      IV insulin or glucose if necessary. At that time a second insulin injection (same dose as at
      time point T= -2 minutes) will be given and a second standardized lunch (mixed) meal will be
      administered. Blood glucose excursions will be followed for an additional 6 hours thereafter
      (T = 780 minutes)

      Conditions for Visits 3-8 will be:

        -  Condition 1. Individualized Lispro ID dose (nominal dose based on prior insulin
           sensitivity testing and patient-specific insulin-to-carb ratio) given immediately (2min)
           prior to a breakfast meal containing predominantly rapidly absorbed carbohydrates (std
           60 g CHO; approximately 70:15:15 CHO:protein:fat); a second lunch mixed meal given 7
           hours later contains the same total number of carbohydrates (std 60 g mixed) but with a
           mixed composition between carbohydrate, protein, and fat (ratio approximately 35:25:40).

        -  Condition 2. Equivalent insulin dose and meal regimen as Condition 1 but given by the SC
           route.

        -  Conditions 3 and 4. The meal regimen from Condition 1, with ID and SC doses increased
           30% above the nominal dose to simulate inappropriate carb counting.

        -  Conditions 5 and 6. The meal regimen from Condition 1, with ID and SC doses decreased
           30% below the nominal dose to simulate inappropriate carb counting.

      In addition during each meal challenge the subject will be maintained on an Animas pump
      intradermally delivering a combined bolus and basal profile of a placebo (5% dextrose for
      injection solution) during the study period to evaluate flow biomechanics.

      Visit 9 will examine a single earlier dose timing (determined by analysis of the glycemic
      profile dataset from the prior 8 visits) relative to the two meals for the ID route only,
      using the optimal target dose from conditions 1 and 2.

      Patients will have a final examination, Visit 10, immediately following Visit 9.
    

Intervention name(s): BD Research Catheter with 34G x 1.5 mm needle; Subcutaneous delivery of insulin using Disetronic Accu-Chek Rapid D infusion set
Intervention type(s): Device; Device
Intervention description(s): bolus injection of insulin given intradermal prior to standardized meal; bolus delivery of insulin given subcutaneously prior to standardized meal
Other intervention name(s): Disetronic Accu-Chek Rapid D infusion set - 6mm cannula
Intervention MeSH terms: Insulin
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: Diabetes; Insulin; Blood Glucose