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

Sponsors and Collaborators:	University of Pittsburgh Pfizer
Information provided by:	University of Pittsburgh
ClinicalTrials.gov Identifier:	NCT00315952

Purpose

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.

Condition	Intervention	Phase
Type 1 Diabetes Mellitus	Drug: Exubera	Phase IV

MedlinePlus related topics: Diabetes Diabetes Type 1

Drug Information available for: Insulin Dextrose

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control, Crossover Assignment, Safety/Efficacy Study
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

Further study details as provided by University of Pittsburgh:

Primary Outcome Measures:

To perform positron emission tomography (PET) imaging of [18F]-fluoro-deoxy-glucose (FDG) uptake by muscle, following administration of a single dose of inhaled compared to infused insulin in volunteers with type 1 diabetes

Secondary Outcome Measures:

To determine overnight rates of glucose production and plasma glucose after a single pre-dinner dose of inhaled compared to IV infused insulin in volunteers with type 1 diabetes

Estimated Enrollment:	12
Study Start Date:	April 2006
Study Completion Date:	December 2006

Detailed 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:

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.
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.
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.

Eligibility

Ages Eligible for Study:	18 Years to 50 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Ages 18 to 50 years old
Body mass index (BMI) 20 to 27 kg/m2 and a total body weight > 50 kg (110 lbs)
Blood pressure: systolic < 150; diastolic < 95.
Type 1 DM
Have diagnosed diabetes type 1 for a minimum of 12 months prior to study entry
In good general health with no evidence or history of clinically significant hematological, renal, endocrine (other than diabetes), pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing)
Hematocrit (Hct) > 34%
ALT < 60; AST < 60
Alkaline phosphatase (Alk Phos) < 150
Sensitive thyroid-stimulating hormone (sTSH) < 6
Fasting (morning) glucose 100-160 mg/dl
Documented hemoglobin A1c (HbA1c) < 7.5% at time of entry
Triglycerides < 175
Cholesterol < 275

Exclusion Criteria:

Exclude if unable to master use of the inhalation device after 3 attempts
Exclude if positive urine drug screen
Exclude if any episodes of severe hypoglycemia in the past 3 months
Exclude if pregnant or breastfeeding or unwilling to use an acceptable method of non-hormonal contraception from at least 14 days prior to the first dose of Exubera® until study is completed.
Exclude if any history of (h/o) asthma or chronic obstructive pulmonary disease (COPD)
Exclude if forced expiratory volume in one second (FEV1) or forced vital capacity (FVC) < 70% predicted
Exclude if treatment with an investigational drug within 30 days preceding the first dose of trial medication.
Exclude if blood donation of approximately 1 pint (500 mL) within 56 days prior to dosing
Exclude if unable or unwilling to comply with the protocol as written
Exclude if any use of tobacco or nicotine containing products within the past 6 months
Exclude if history of regular alcohol consumption exceeding 7 drinks/week for females or 14 drinks/week for men (1 drink = 5 ounces of wine or 12 ounces [360 mL] of beer or 1.5 ounces [45 mL] of hard liquor) within 6 months of screening
Exclude if claustrophobic, any surgical or vascular implants or pacemakers, or any metal in the body

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00315952

Locations

United States, Pennsylvania
University of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15213

Sponsors and Collaborators

University of Pittsburgh

Pfizer

Investigators

Principal Investigator:

David E. Kelley, MD

University of Pittsburgh

More Information

Study ID Numbers:	06020777
Study First Received:	April 17, 2006
Last Updated:	February 15, 2008
ClinicalTrials.gov Identifier:	NCT00315952
Health Authority:	United States: Institutional Review Board

Keywords provided by University of Pittsburgh:

type 1 diabetes mellitus
inhaled insulin
Positron Emission Tomography

Study placed in the following topic categories:

Autoimmune Diseases
Metabolic Diseases
Diabetes Mellitus, Type 1
Diabetes Mellitus
Endocrine System Diseases

Endocrinopathy
Metabolic disorder
Glucose Metabolism Disorders
Insulin

Additional relevant MeSH terms:

Immune System Diseases

ClinicalTrials.gov processed this record on January 16, 2009