Study to Estimate the Effects of Inhaled Versus Intravenous (IV) Infusion of Human Insulin in Subjects With Type 1 Diabetes

Type 1 Diabetes Mellitus Clinical Trial

Official title: Open-Label Randomized Two-Way Crossover Pilot Study to Estimate the Effects of Inhaled vs. IV Infusion of Human Insulin With Regards to Glucose Disposal in Subjects With Type 1 Diabetes Mellitus

Status Completed

Clinical Trial Summary

University of Pittsburgh Medical Center (UPMC) diabetes research physicians are studying the action in muscle tissue of "inhaled" insulin (Exubera®) and "infused" (intravenous or IV) insulin on blood sugar control in people with type 1 diabetes. Type 1 diabetics often take 2-4 shots of insulin every day. Exubera may offer an alternative to these insulin injections.

Clinical Trial Description

A dry powder insulin formulation delivered by an aerosol inhaler has been in clinical development for use in types 1 and 2 diabetes mellitus (DM) and just recently (1-27-06) received approval from the U.S. Food and Drug Administration (FDA) for the clinical treatment of diabetes. Administration of insulin without the need for subcutaneous (SC) injection is an attractive alternative for patients with diabetes. There are preclinical and clinical data that indicate inhalation of insulin results in a more potent effect on glucose disposal and a lower fasting glucose than is attained with equivalent dosing of SC or intravenous (IV) insulin. The physiological mechanism(s) are unclear, but occur even when matched for pharmacokinetics.

The current proposal seeks primarily to more fully delineate whether there are physiological differences in the metabolic effects of inhaled compared to IV infused insulin, giving IV insulin to match the pharmacokinetics (PK) achieved with inhaled insulin.

There are 3 specific aims:

1. The first aim is to establish a protocol for matching the PK of inhaled insulin with the PK of intravenously infused insulin. An infusion algorithm has been developed and will be tested and refined in healthy volunteers (n = 3-5), and will be used for the physiological studies (aims) outlined below.

2. The second aim is to perform Positron Emission Tomography (PET) imaging of [18F]-FDG uptake by muscle, following administration of a single dose of inhaled compared to infused insulin. Volunteers with type 1 DM (n =12) will be studied, serving as his/her within-subject control, under each condition of insulin administration.

In these type 1 diabetes mellitus (type 1 DM) volunteers, we will test the hypothesis that a single dose of inhaled versus infused insulin, matched for arterial concentrations, causes greater stimulation of muscle glucose uptake.

3. The third aim is to determine overnight rates of glucose production and plasma glucose after a single pre-dinner dose of inhaled compared to IV infused insulin. The same 12 volunteers studied for Aim 2 will be studied the evening preceding the PET imaging studies and will serve as his/her within-subject control, under each condition of insulin administration. ;

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Type 1 Diabetes Mellitus

• NCT number: NCT00315952
• Study type: Interventional
• Source: University of Pittsburgh
• Status: Completed
• Phase: Phase 4
• Start date: April 2006
• Completion date: December 2006