Pharmacokinetics/Dynamics of Basal (Continuous) Insulin Infusion Administered Either Intradermally or Subcutaneously
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.
|Diabetes Mellitus, Type 1 Diabetes Mellitus, Type 2||Device: Intradermal insulin delivery: BD Research Catheter Set Device: Subcutaneous insulin delivery:ACCU-CHEK Rapid-D Infusion Set||Phase 1 Phase 2|
|Study Design:||Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
|Official Title:||A Mono-center, Open Label, Randomised 2-period Crossover Study to Compare the Pharmacokinetics and Pharmacodynamics of Continuous Insulin Infusion Administered Either Intradermally or Subcutaneously in Subjects With Type 1 Diabetes Mellitus|
- Insulin measurements will be used to compute PK model parameters: absorption rate(s) and elimination rate using an appropriate transport model. [ Time Frame: 20 hours ]
- Pharmacodynamic glycemic parameters will be as follows: time from insulin infusion onset to glycemic nadir; time from test insulin shutoff to return to baseline glucose; amount of additional drop in blood glucose following test insulin infusion shutoff [ Time Frame: 20 hours ]
- Evidence of safety and tolerability of intradermally infused insulin [ Time Frame: 26 hours ]
- Feasibility of RCS for longer-term ID infusion [ Time Frame: 16 hours ]
|Study Start Date:||January 2010|
|Study Completion Date:||March 2010|
|Primary Completion Date:||March 2010 (Final data collection date for primary outcome measure)|
|Experimental: Intradermal insulin infusion (ID)||
Device: Intradermal insulin delivery: BD Research Catheter Set
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)
|Active Comparator: Subcutaneous insulin infusion (SC)||
Device: Subcutaneous insulin delivery:ACCU-CHEK Rapid-D Infusion Set
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)
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.
- 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.
- 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
Please refer to this study by its ClinicalTrials.gov identifier: NCT01061216
|Profil Institut für Stoffwechselforschung GmbH|
|Neuss, Germany, D-41460|
|Principal Investigator:||Christoph Kapitza, Dr. med.||Profil Institut für Stoffwechselforschung GmbH|