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

This study has been completed.
Sponsor:
Collaborator:
Pfizer
Information provided by:
University of Pittsburgh
ClinicalTrials.gov Identifier:
NCT00315952
First received: April 17, 2006
Last updated: February 15, 2008
Last verified: February 2008
  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 4

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

Resource links provided by NLM:


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:

  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.
  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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

No publications provided

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

Keywords provided by University of Pittsburgh:
type 1 diabetes mellitus
inhaled insulin
Positron Emission Tomography

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Insulin, Globin Zinc
Insulin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 28, 2014