Pharmacokinetics/Dynamics of Basal (Continuous) Insulin Infusion Administered Either Intradermally or Subcutaneously
Condition: Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Diabetes Mellitus, Type 1
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      The primary objective of this study will be to assess the PK/PD responsiveness of basal ID
      administered insulin compared to SC, and to determine the safety and local tolerability of
      extended (two six-hour periods) microneedle insulin delivery (MID) infusion. The primary
      endpoint will be the PK response to changes in rapid-acting insulin basal infusion rate.

      Faster PK transitions coupled with faster PD responsiveness could provide clinical benefit,
      compared to current subcutaneous insulin infusion. In addition, for nocturnal basal pumping,
      more rapid insulin offset could decrease the occurrence rate and severity of hypoglycemic
      episodes.
    

Detailed description: 
      Twenty (20) male T1 diabetic subjects will be studied under manual partial glucose clamp
      conditions over a 16 hour infusion period (approximately 36 hours of overall time in clinic).
      Subjects will be admitted to the clinic the night before their study visit for overnight
      stabilization in which, via insulin and/or glucose infusions, blood glucose will be
      stabilized to approximately 140 mg/dL. Subjects will receive as background IV Humulin insulin
      with an initial dose equivalent to one-half of their usual daily basal insulin dose. In the
      morning the subjects will start the experimental intervention and have administered a low
      rate stair-stepped Lispro insulin infusion profile via an infusion pump (Harvard Syringe
      Pump, Harvard Apparatus).

      The profile is designed to examine the initial "on" rate for microneedle insulin delivery,
      the transition time between basal rate changes and the "off-rate" after insulin cessation.
      Subjects will receive the same profile by SC infusion on a second clinic day in a randomized
      order. PK endpoints will be established using timed blood samples. Safety and tolerability at
      the local infusion site will also be recorded.

      In parallel, using a commercially available insulin pump (One Touch "Ping" Insulin Pump,
      Animas) and an infusion set (either the RCS or a commercially available SC insulin infusion
      set); a second infusion of insulin diluent will be used to assess the feasibility of
      longer-term ID infusions (16 hours) as compared to SC.

      During each infusion the pumps will control the fluid delivery rate and volume. In addition
      an in-line pressure transducer will record the pressure and transfer the information to a
      laptop computer.

      Primary Objective:

        -  To define the PK profile of initiation, rate change, and discontinuation of continuously
           infused basal insulin administered either intradermally or subcutaneously over two
           separate infusion periods.

      Secondary Objectives:

        -  Determine the PD effect of the infused insulin as measured by time to glucose rebound
           following discontinuation of test insulin infusion.

        -  Assess the safety and tolerability of intradermally infused insulin over two six-hour
           periods.

        -  Assess the feasibility of the research catheter set (RCS) for longer-term ID infusion
    

Intervention name(s): Intradermal insulin delivery: BD Research Catheter Set; Subcutaneous insulin delivery:ACCU-CHEK Rapid-D Infusion Set
Intervention type(s): Device; Device
Intervention description(s): 1 unit/hr rapid acting insulin delivered intradermally for 6 hours 4 hour washout period (no insulin delivered) 2 units/hr rapid acting insulin delivered intradermally for 6 hours 4 hour washout period (no insulin delivered); 1 unit per hour of rapid acting insulin infusion for 6 hours 4 hour washout (no insulin delivered) 2 unit per hour of rapid acting insulin infusion for 6 hours 4 hour washout (no insulin delivered)
Other intervention name(s): ACCU-CHEK; Rapid-D Infusion Set (Disetronic, USA)
Intervention MeSH terms: Insulin; Insulin, Globin Zinc
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: Diabetes; Insulin Therapy; Blood Glucose; Basal insulin; Diabetics